Background. It is unclear whether the use of clinical prediction rules is sufficient to rule out infective endocarditis (IE) in patients with Staphylococcus aureus bacteremia (SAB) without an echocardiogram evaluation, either transthoracic (TTE) and/or transesophageal (TEE). Our primary purpose was to test the usefulness of PREDICT, POSITIVE and VIRSTA scores to rule out IE without echocardiography. Our secondary purpose was to evaluate whether not performing an echocardiogram evaluation is associated with higher mortality. Methods. We conducted a unicentric retrospective cohort including all patients with a first SAB episode from January 2015 to December 2020. IE was defined according to modified Duke criteria. We predefined threshold cut-off points to consider that IE was ruled out by means of the mentioned scores. To assess 30-day mortality, we used a multivariable regression model considering performing an echocardiogram as covariate. Results. Out of 404 patients, IE was diagnosed in 50 (12.4%). Prevalence of IE within patients with negative PREDICT, POSITIVE and VIRSTA scores was: 3.6% (95% CI 0.1-6.9%), 4.9% (95% CI 2.2-7.7%), and 2.2% (95% CI 0.2-4.3%), respectively. Patients with negative VIRSTA and negative TTE had an IE prevalence of 0.9% (95% CI 0-2.8%). Performing an echocardiogram was independently associated with lower 30-day mortality (OR 0.24 95%CI 0.10-0.54, p=0.001). Conclusion. PREDICT and POSITIVE scores were not sufficient to rule out IE without TEE. In patients with negative VIRSTA score, it was doubtful if IE could be discarded with a negative TTE. Not performing an echocardiogram was associated with worse outcomes, which might be related to presence of occult IE. Further studies are needed to assess the usefulness of clinical prediction rules in avoiding echocardiographic evaluation in SAB patients.

Antibiotic therapy is a cornerstone of modern medicine, yet the development of antibiotic re-sistance threatens to render these therapies ineffective. The gut microbiota, a complex ecosystem of microorganisms residing in the gastrointestinal tract, plays a critical role in modulating anti-biotic efficacy and resistance. This review delves into the intricate relationship between gut mi-crobiota, antibiotic therapy, and resistance, and discusses the potential applications of gut mi-crobiota research in guiding personalized antibiotic therapy and resistance mitigation strategies. Recent advancements in metagenomics, metatranscriptomics, and metabolomics have demon-strated the potential for tailored antibiotic regimens that minimize collateral damage to com-mensal bacteria and reduce the risk of resistance. Adjuvant therapies such as probiotics, prebi-otics, and synbiotics have shown promise in restoring gut microbial balance and mitigating the adverse effects of antibiotic therapy. We address the challenges associated with this emerging field including the need for standardized methodologies, ethical considerations, and interdisci-plinary collaboration. With continued interdisciplinary collaboration and the implementation of standardized methodologies, gut microbiota research can contribute to the global fight against antibiotic resistance and improve patient outcomes.

Background: Effectiveness of Anastrozole and levonorgestrel-releasing intrauterine device (LNG-IUD, Mirena®) in the treatment of endometriosis. Methods: Randomized clinical trial. Elegibility criteria: Endometriomas >3×4 cm, CA-125>35 U/mL and symptoms suggestive of endometriosis. Thirty-one women were randomized to anastrozole+Mirena®+Conservative Surgery(CS) (n=8), anastrozole+Mirena®+transvaginal ultrasound-guided puncture-aspiration(TUGPA) (n=7), Mirena®+CS (n=9), or Mirena®+TUGPA (n=7). Interventions: Anastrozole 1 mg/day and/or only Mirena® for 6 months. CS or TUGPA one month after starting medical treatment. Results: A significant improvement in symptoms during the treatment (difference of 43%, 95% CI 29.9-56.2) occurred, which was maintained at 1 and 2 years. It was more significant in patients treated with anastrozole. For CA-125, the most significant decrease was observed without anastrozole. After CS for endometriosis, a reduction of findings of endometriomas and long-term recurrences occurred, with or without anastrozole, although anastrozole seems to delay recurrences. At 4,2±1,7 years, 88% of the patients who underwent CS were asymptomatic, compared to only 21% if TUGPA was performed, with or without anastrozole (p=0.019). Conclusion: Dosing anastrozole for 6 months, starting one month before CS of endometriosis, reduces more significantly the painful symptoms and delays recurrences, but has no other significant advantages over the single insertion of LNG-IUD (Mirena®) during the same time.

Probiotics have been widely used in gastroenteritis due to acute and chronic illnesses. However, evidence supporting the effectiveness of probiotics in different health conditions are inconclusive and conflicting. The aim of the study was to review existing literature on the effects of probiotics in gastroenteritis among adults. Only original articles on clinical trials that demonstrated the effects of probiotics in adults with gastroenteritis were used for this analysis. Multiple databases such as PubMed, Google Scholar, MEDLINE and Scopus databases were searched for the data. The study followed standard procedures for data extraction using PRISMA flow chart. A quality appraisal of the selected studies was conducted using CADIMA. Finally, a meta-analysis was conducted. Thirty-five articles met the selection criteria; of them, probiotics were found effective in the treatment and/or prevention of chronic inflammatory bowel disease (IBD) including ulcerative colitis and Crohn’s disease in 17 (49%), and the treatment of pouchitis in 4 (11.4%), antibiotic-induced diarrhea in 3 (8.6%), Helicobacter pylori infection in 2 (5.7%) and diverticulitis in 1 (2.9%), while the remaining 7 (20%) were ineffective and 1 study results were inconclusive. Meta-analysis, on the contrary, didn’t demonstrate any significant protective effects of probiotics. Having a τ² value of zero and I² of 6%, the studies were homogeneous and had minimum variances. Further studies are suggested to evaluate the beneficial effects of probiotics in IBDs and other chronic bowel diseases.

Background: About 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. Methods: This retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. Results: (GU, N=66, 2,3%), Beckwith-Wiedemann spectrum (BWS, N=32, 1,1%), isolated hemihypertrophy (IHH, N=29, 1,0%), Denys-Drash syndrome (DDS, N=24, 0,8%) and WAGR syndrome (N=20, 0,7%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24,5 months vs. 39,0 months), had smaller tumors (334,8mL vs. 496,9mL), less often metastasis (8,2% vs. 18%), but more often nephroblastomatosis (12,9% vs. 1,9%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30%), DDS (29%) and BWS (31%). Chemotherapy induced reduction in tumor volume was poor in DDS (7,7% increase) and favorable in BWS (84,6% reduction). The event-free survival (EFS) of patients with BWS was significantly (p=0,002) worse than in others. Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable.

The morbidity and mortality caused by invasive fungal infections is increasing across the globe due to developments in transplant surgery, the use of immunosuppressive agents, and the emergence of drug-resistant fungal strains, which has led to a challenge in terms of treatment due to the limitations of three classes of drugs. Hence, it is imperative to establish effective strategies to identify and design new antifungal drugs. Drug repurposing is an effective way of expanding the application of existing drugs. In the last years, various existing drugs have been shown to be useful in the prevention and treatment of the invasive fungi. In this review, we summarize the currently used antifungal agents. In addition, the most up to date information on the effectiveness of existing drugs with antifungal activity is discussed. Moreover, the antifungal mechanisms of existing drugs are highlighted. These data will provide valuable knowledge to stimulate further investigation and clinical application in this field.

The epidemiological and clinical pathological aspects of polioencephalomalacia (PEM) in five buffaloes (buffaloes 01 to 05) in the amazon biome are described. Epidemiological data were obtained during the clinical visit in which the animals with clinical signs compatible with polioencephalomalacia were submitted to a general and specific clinical examination of the nervous system. During the necropsy of the five animals, the intensity and location of the lesions were evaluated and fragments from different organs were collected and fixed in 10% buffered formalin and sent to the Pathological Anatomy Sector of the Federal Rural University of Rio de Janeiro for histopathological examination. Of the five studied animals, all were of the Murrah breed, four male and one female, with ages ranging from two months to one year. Two buffaloes (buffalo 01 and 02) were from the municipality of Castanhal, Pará, kept in an extensive breeding system on Urochloa brizantha pasture. Buffaloes 03 and 04 belonged to a property located in the municipality of Cachoeira do Arari, Marajó Island, Pará, and buffalo 05 was from a property located in the municipality of Itaubal, state of Amapá, all of them were raised in an extensive system in flooded of native pasture. At the clinical examination, all buffaloes had a body score between 2.5 and 3 (scale from 1 to 5), and there was noted decreased alertness, postural changes, marked hypermetria when stimulated to move, total or partial blindness demonstrated by colliding to the corral structures, head pressing and circumduction of the hindquarters when supported on the forelimbs, opisthotonos, muscle tremors, convulsions, paddling movements, sialorrhea, decrease in palpebral and pupillary reflexes and eyeball rotation placing the pupillary slit in a vertical position. At necropsy, mild lesions characterized by edema and flattening of the cerebral convolutions were observed. Histopathological examination showed laminar necrosis of the cerebral cortex. The diagnosis of polioencephalomalacia was based on epidemiological, clinical-pathological, and histopathological findings, similar to findings in other ruminants. The cause of polioencephalomalacia in the studied buffaloes was not established, which indicates the need for further studies to elucidate this disease in the species, mainly in the Amazon region.

Background: Severe eosinophilic asthma (SEA) represents a substantial global health burden. Benralizumab has been shown to restore good control of asthma. Robust data on benralizumab effectiveness over periods longer than 2 years are still scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Clinical outcomes were evaluated at 6, 12, 24 and 36 months. Partial and complete clinical remission (CR) were also assessed. Data were analysed either with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: Benralizumab induced a persistent reduction in exacerbation rates (p

The overall objective of this mixed-method digital-based observational study was to determine the mental health impact among CTU staff working during the COVID-19 pandemic. The Qualtrics Core XM platform was used to deploy the questionnaire where a quantitative analysis was conducted. The qualitative part of the study used the Microsoft Teams digital application to complete the interviews. Various validated mental health assessments were administered: Vancouver Index of Acculturation (VIA), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), Pandemic Stress Index (PSI), Burnout Assessment Tool-12 (BAT-12), General Self Efficacy Scale (GSE) and The Everyday Discrimination Scale (EDS). A total of 485 participants took part, of which 73.4% were female and 70.1% of the sample were white British. A high prevalence of anxiety, exhaustion and depression were identified across all participants. A significant mental health impact was identified among the CTU workforce where wellbeing was compromised during the course of the COVID-19 pandemic.

High-fidelity patient simulation (HFPS) is widely used in professional training to enhance students’ competence in clinical management. Problem-solving (PS) and clinical reasoning (CR) skills are essential to developing students in professional competence in safe and effective care. These two skills should be initiated at the early training. However, little is known about the effects of HFPS on developing PS and CR skills in first year undergraduate students. Therefore, this pre- and post-experimental study aimed to investigate the effects of HFPS on development of PS and CR skills in first-year nursing students. The students were required to go through four sessions, preparation, pre-briefing and orientation, simulation role-playing, and debriefing, for the HFPS. The study utilized the Problem-Solving Inventory (PSI) and the Nurses Clinical Reasoning Scale (NCRS) to measure problem-solving and clinical reasoning abilities before and after HFPS. Bivariate analysis, one-sample t-test, and independent t-test were performed to evaluate the performance of the PS and CR skills at the two study periods. One hundred eighty-nine students were recruited, with a mean age of 20.56 years, and 73% were female students. The analytic results showed that the PSI, particularly in domains of Problem-Solving Confidence (PSC) (p<0.001) and overall PS (p<0.001), and the CR (p<0.001) had significant improvement after HFPS. The study concluded that HFPS is an effective innovative method to significantly improve students’ problem-solving and clinical reasoning abilities. Nurse educators play an important role in providing explicit learning instructions in a simulation guideline that directs and guides students to learn at each stage of HFPS. Students should take more initiative and engage in their learning through HFPS to enhance their competence in knowledge and higher intellectual skills for personal and professional developments.

Background: Chikungunya virus (CHIKV) diagnosis have become a challenge for primary care physicians in areas where zika virus and/or dengue virus are present. Case definitions for the three arboviral infections are overlapping. Methods: A cross-sectional analysis was carried out. A bivariate analysis was made using confirmed CHIKV infection as the outcome. Variables with significant statistical association were included in an agreement consensus. Agreed variables were analyzed in multiple regression model. The area under the receiver operating characteristic (ROC) curve was calculated to determine a cut-off value and performance. Results: 295 patients with confirmed CHIKV infection were included. A screening tool was made using symmetric arthritis (4 points), fatigue (3 points), rash (2 points) and ankle joint pain (1 point). The ROC curve identified a cut-off value and a score ≥ 5.5 was considered positive to identify CHIKV patients with a sensibility of 64.4% and a specificity of 87.4%, positive predictive value of 85.5%, negative predictive value of 67.7%, area under the curve of 0.72, and an accuracy of 75%. Conclusion: We developed a screening tool for CHIKV diagnosis using only clinical symptoms as well as proposed an algorithm to aid the primary care physician.

The purpose of this systematic review is to examine the various articles published in the field of neuropsychology of anxiety research in terms of publication type and volume, methodology, and subject matter. The significance of this topic derives from the clinical and functional consequences of cognitive symptoms. Generalized anxiety disorder refers to the cluster of clinical symptoms characterized by predominant anxious anticipation and difficulty controlling worry. In order for the review to be systematic and reproducible, a search of the PsycINFO, Scopus, PubMed, Elsevier databases and an analysis using the PRISMA method are suggested. After analyzing the research data, empirical studies evaluating the clinical neuropsychology of generalized anxiety disorder are discussed.

The emergence of acute, severe non hepA–E hepatitis of unknown etiology (ASHUE) has attracted global concern owing to the very young age of the patients and its unknown etiology. Although this condition has been linked to several possible causes, including viral infection, drugs, and/or toxin exposure, the exact cause remains unknown; this makes treatment recommendations very difficult. In this review, we summarize recent updates on the clinical manifestations, complemented with laboratory results, case numbers with the global distribution and other epidemiological characteristics, and the possible etiologies. We also provide the proposed actions that could be undertaken to control and prevent further spread of this hepatitis. Since many etiological and pathological aspects of the acute non hepA–E hepatitis remain unclear, further research is needed to minimize the severe impact of this disease.

Clopidogrel is one of the most prescribed antiplatelet drugs for cardiovascular diseases prevention. Clopidogrel is a prodrug metabolised by CYP2C19 in active metabolites with anti-aggregant effect. Pharmacogenetic variants such as CYP2C19*2 variant can alter the anti-aggregant effect of clopidogrel leading to a higher risk of cardiovascular disease relapse. The aim of this study was to evaluate the prescription characteristics of CYP2C19 pharmacogenetics in patients on clopidogrel treatment, based on a specific query in a clinical data warehouse. We evaluated the demographics of patients, prescribers, medical indications, CYP2C19 pharmacogenetic tests and therapeutic changes. Neurologists were the main prescribers of CYP2C19 pharmacogenetic tests associated with clopidogrel treatment in a context of suspicion of stroke relapse. Pharmacogenetic tests were mainly prescribed a posteriori to clopidogrel prescription. Clopidogrel pharmacogenetic resistance was associated with the prescription of lysine acetylsalicylate in substitution of clopidogrel. Clear clinical practice guidelines are needed to position CYP2C19 pharmacogenetic testing for patients on clopidogrel treatment.

Ketamine as an old - new drug has variety of clinical implications. In the last 30 years, ketamine has become popular for acute use in humans. Ketamine at standard doses is principally utilized for the induction and maintenance in surgical procedures. Beside its use in anesthesia and analgesia, recently studies had shown that ketamine find the place in the treatment of asthma, epilepsy, depression, bipolar affective disorders, alcohol and heroin addiction. Its mechanism of action is complex, but it mostly acts as a noncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor. Ketamine is generally considered relatively secure and does not result in serious adverse effects when used at low doses and for short periods- Also, ketamine is known as a powerful psychostimulant. During the past decade, ketamine has been one of the commonly abused drug.

Background: Transient Hypogammaglobulinemia of Infancy (THI) is a primary immunodeficiency caused by a temporary decline of serum levels of immunoglobulin G (IgG) greater than 2 standard deviations below the mean age-specific reference values in an infant between 5 and 24 months of age. Preterm infants are particularly susceptible to THI, as, in the third trimester of pregnancy, IgG is transferred across the placenta from mother to infant.Objective: To systematically review the diagnostic criteria of Transient Hypogammaglobulinemia of infants.Design & Methods: Systematic Review. Manual searching of 3 electronic databases (PubMed, Medline, & Google Scholar) from September 2021 – April 2022. Abstracts were screened to assess fit to the inclusion criteria. Data was extracted from the selected studies by using an adapted extraction tool from Cochrane.org. Studies were then assessed for bias by using an assessment tool also adapted from Cochrane.org.Results: Of the 215 articles identified, 16 were eligible for examining the diagnostic criteria of THI. These studies were also assessed for bias in 6 domains. 5 studies (31%) had a low risk of bias, while 4 studies (25%) had a high risk of bias, & 7 studies (44%) were unclear for bias.Conclusion: We can conclude that THI is only definitively diagnosed after the abnormal IgG levels have normalized, hence THI is mostly a benign condition, but must be monitored for subsequent recurrent infections. The diagnostic criterion also includes vaccine & isohaemagglutinin responses to differentiate against other immunological disorders in infants.

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer deaths worldwide. Surgery or surgery plus radiotherapy and/or chemotherapy for patients with metastatic CRC (mCRC) were accepted as the main therapeutic strategies until the early 2000s, when targeted drugs, like cetuximab and bevacizumab were developed. The use of targeted drugs in clinical practice has significantly increased patients’ overall survival. To date, the emergence of several types of targeted drugs has opened new possibilities and revealed new prospects for mCRC treatment. Therapeutic strategies are continually being updated to select the most suitable targeted drugs based on the results of clinical trials that are currently underway. This review discusses the up-to date molecular evidence of targeted therapy for mCRC and summarizes the Food and Drug Administration-approved targeted drugs including the results of clinical trials. We also explain their mechanisms of action and how these affect the choice of a suitable targeted therapy.

Background: Kawasaki disease (KD) is a form of vasculitis that primarily affects children under the age of 5 years old. Patients may be missed diagnosis when initial clinical symptoms do not fulfill the traditional criteria. We aimed to analyze factors that clinicians could use to differentiate febrile children suspected of KD. Method: We retrospectively enrolled a total of 83 febrile children who were initially suspected of KD, but they did not meet the American Heart Association (AHA) criteria for a diagnosis. However, some of these patients were diagnosed with KD during their second visit. We analyzed patients' characteristics, clinical symptoms, and laboratory data. Results: In total, 50 patients were enrolled in the study. Of those, ten patients were diagnosed with KD on their second visit (group 1), while the other 40 patients still did not fit a KD diagnosis (group 2). A patient with a neutrophil to lymphocyte ratio greater than 1.33 combined with a C-reactive protein more than 33 mg/L was more likely to have KD. Conclusion: Among patients suspected of KD that did not initially meet the criteria, clinicians should pay special attention to elevated neutrophil-to-lymphocyte ratios and CRP levels and closely follow up such patients.

Clinical training in medical schools in Spain is performed by rotations in university hospitals. During these internships, students are expected to acquire and master basic procedural skills. However, the assessment tools available rarely check whether these skills are completely acquired by the students. We have used an e-portfolio to determine the optimal number of times the students need to repeat a procedure to be able to perform it independently. The results were compared with the actual performance during the internships. An e-portfolio collected qualitative information about the internships. Quantitative information was also requested about the number of times each clinical skill was performed. Later, a survey asked these students and their teachers the optimal number of times each skill should be repeated before it could be considered fully acquired. The questionnaire was answered by 98.6% of the students and 70.3% of their teachers. Out of the 21 clinical skills and procedures selected, both students and their tutors agreed in a similar optimal value in 16 of them; only in five of them, teachers thought that students needed a greater number of times than that selected by the students. When these optimal values were compared with the actual values recorded in the portfolio during the internships, it was found that about half of the clinical skills were carried out less frequently than expected, thus providing an important feedback about the internships. Quantitative information collected in portfolios reveals a moderate mismatch between students and tutors perceptions of their training needs.

Hashimoto’s thyroiditis (HT) is a gender autoimmune disease that is manifested by chronic inflammation of thyroid. Clinical trial studies (CTSs) use molecular biotechnologies (MB) to approach HT appearance. Aims of this study was to analyze the applications of MB in CTSs carried out in HT populations (HT-CTSs). Further, to evaluate the role of MB in the context of hygiene hypothesis (HH). From 75 HT-CTSs found at https://beta.clinicaltrials.gov/ web place, forty-five were considered for this investigation. Finally, six HT-CTSs were reported as molecular HT-CTSs (mHT-CTSs) because of these were planning to utilize MB. Two of mHT-CTSs were settled on French population to isolate DNA viral sequences. Blood, urine, and thyroid tissues biospecimens were analyzed to pick out parvo and polyoma viruses. Two mHT-CTSs carried out in China, were aimed to identify oral and fecal microbiotas by measuring PCR sequencing of 16S rRNA gene. Two mHT-CTSs were programmed in USA and Greece, respectively, for interception of DNA polymorphisms to associate with genetic susceptibility to HT. In conclusion, MB are mainly employed in HT-CTSs for infective pathogenesis and genetic fingerprinting of HT. Besides, MB don't prove the evidence of HH; however, they are useful for direct evidence of the presence of viruses.

The changing epidemiology of Staphylococcus aureus has created several gaps in its population structure and emergence of strains. Two global shifts in the aftermath of the past methicil-lin-resistant S. aureus (MRSA) pandemic are: a rise in healthcare-associated infections and evolu-tion of cutaneous and soft tissue infections with high morbidities and mortalities. Furthermore, bitter lessons from COVID-19 showed S. aureus necrotizing-pneumonia and skin conditions ag-gravating Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Monkeypox manifestations. Limited data and paucity of high-quality evidence exist for many key clinical questions. Using clinical microbiology, molecular characterization, hospital data on age and in-fection sites, and antibiograms, we have investigated S. aureus infection patterns. We showed that age-specific distribution in both intensive care unit (ICU) and non-ICU revealed highest infection rates (94.7%) in senior-patients >50 years; most were MRSA (81.99%). However, specific distribu-tions of geriatric MRSA and MSSA rates were 46.5% and 4.6% in ICU and 35.48% and 8.065% in non-ICU, respectively. Intriguingly, age groups 0-20 years showed uniquely similar MRSA pat-terns in ICU and non-ICU patients (13.9%, 9.7%, respectively) and MSSA in ICU (11.6%). In age groups 20-50 years, MRSA were 2-fold in non-ICU (35%) than ICU (18.6%). Interestingly, highly significant association was found between infection-site and age-groups (P-value .000). Skin in-fections remained higher in all ages; pediatrics 32.14%, adults 56%, and seniors 25% while res-piratory infections were lower in pediatrics (14.3%) and adult 17%), and highest in seniors (38%). Blood and “other” sites in pediatrics recorded (28.6%; 25%, respectively), slightly lower in adults (18.6%; 8.6%) and seniors (14%); 22.8%), respectively. Further, significant association existed between infection-site and MRSA (Chi-Square Test, P-value .002). The common cutaneous infec-tions across all age-groups and the significant association of MRSA to geriatric-respiratory infec-tions have a high potential for skin-carriage as reservoir for endogenous infection. The similar frequencies of both lineages in youth in all settings imply MSSA-carriage as potential evolutionary origins for MRSA. These findings have important clinical implications for strategic planning in patient management and S. aureus control particularly in age-specific infections and vigilance for potential viral coinfections.

Background. Until now, cost of allergy treatment in insured public health care system and non-insured self-financing private health care system in Indonesia has not been well documented and published, as well as the cost of allergy treatment with subcutaneous immunotherapy. Objective. To evaluate the clinical and cost benefits of allergic rhinitis treatment in children with subcutaneous immunotherapy in non-insured self-financing private health care system. Methods. A retrospective cohort study conducted from 2015 until 2020, compared clinical improvement and health care costs over 18 months in newly diagnosed AR children who received SCIT versus matched AR control subjects who did not receive SCIT, with each group consisting of 1,098 subjects Results. Decrease of sp-HDM-IgE level (kU/ml) from 20.5 + 8.75 kU/ml to 12.1 + 3.07 kU/ml had been observed in the SCIT group. To reduce the symptom score of allergic rhinitis by 1.0 with SCIT it costs IDR 21,753,062.7 per child, for non SCIT it costs IDR 104,147,878.0 per child. Meanwhile, to reduce the medication score (MS) by 1.0 with SCIT it costs Rp. 17,024,138.8 while with non SCIT it costs Rp. 104,147,878.0. Meanwhile, to lower combination symptoms and medication score (CSMS) by 1.0, with SCIT it costs IDR 9,550,126.6, while with non SCIT it costs IDR 52,073,938.9. Conclusion. In conclusion, this first Indonesia-based study demonstrates substantial health care cost savings associated with SCIT for children with AR in an uninsured private health care system and provides strong evidence for the clinical benefits and cost-savings benefits of AR treatment in children.

Genetic testing allows for identification of germline DNA variations which are associated with a significant increase in risk of developing breast and ovarian cancer. Detection of a BRCA1 or BRCA2 pathogenic variant triggers several clinical management actions, which may include increased surveillance and prophylactic surgery for healthy carriers or treatment with PARP inhibitor therapy for carriers diagnosed with cancer. Thus, standardized validated criteria for annotation of BRCA1 and BRCA2 variants according to their pathogenicity are necessary to support clinical decision making and ensure improved outcomes. Upon detection, variants whose pathogenicity can be inferred by the genetic code are typically classified as pathogenic, likely pathogenic, likely benign, or benign. Variants whose impact on function cannot be directly inferred by the genetic code are labeled as Variants of Uncertain Clinical Significance (VUS) and are evaluated by multifactorial likelihood models that use personal and family history of cancer, segregation data, prediction tools, and co-occurrence with a pathogenic BRCA variant. Missense variants, coding alterations that replace a single amino acid residue with another, are a class of variants for which determination of clinical relevance is particularly challenging. Here, we discuss current issues in variant classification by following a typical life cycle of a BRCA1 missense variant through detection, annotation and information dissemination. Advances in massively parallel sequencing have led to a substantial increase in VUS findings. Although comprehensive assessment and classification of missense variants according to their pathogenicity remains the bottle neck, new developments in functional analysis, high throughput assays, data sharing, and statistical models are rapidly changing this scenario.

Glioblastoma (GBM) is the most lethal form of brain tumor, characterized by rapid growth and surrounding tissue invasion. The current standard treatment is surgery followed by radiotherapy, and concurrent chemotherapy, typically with temozolomide. Although extensive research has been performed over the past years to develop an effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in the overall survival of patients with GBM. Thus, new therapeutic approaches are urgently needed. A major challenge in the development of therapies for central nervous system (CNS) disorders is overcoming the blood–brain barrier (BBB). In this context, the intranasal (IN) route of drug administration has been proposed as a non-invasive alternative route to directly targeting the CNS. In fact, this route of drug administration may bypass the blood-brain barrier and reduce systemic side effects. Recently, formulations have been developed to further enhance nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review will be on the strategies developed to deliver a number of anticancer compounds for the treatment of GBM using the nasal administration. In particular, the specific properties of nanomedicines proposed for the nose-to-brain delivery will be critically evaluated. The number of preclinical and clinical data reviewed support the idea that nasal delivery of anticancer drugs might represent a breakthrough advancement in the fight against GBM.

Since the effects of renin–angiotensin–aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting in different studies, we performed this meta-analysis. A systematic search of published articles was performed in PubMed and EMBASE from January-May 5, 2020. Studies that reported the clinical outcomes of patients with COVID-19, stratified by the class of concomitant antihypertensive drug therapy, were included. The Mantel-Haenszel random effects model was used to estimate pooled odds ratio (OR). A total of 6,997 hypertensive patients with COVID-19 were included. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR=0.84, 95% CI: [0.73, 0.96]; P=0.017) compared with those receiving non-RAAS inhibitor antihypertensives. Patients taking angiotensin-I-converting enzyme inhibitors (ACEIs) were less likely to experience poor clinical outcomes (OR=0.73, 95% CI: [0.58-0.92]; P=0.01) compared with those receiving angiotensin-II receptor blockers (ARBs). Compared to all other antihypertensives, ACEIs decreases the risk poor COVID-19 outcomes (OR=0.77, 95% CI: [0.63-0.93]) while ARBs did not (OR=1.13, 95% CI: [0.95-1.35]). The risk of poor patient outcomes from COVID-19 was lower in patients who received RAAS inhibitors compared with those who took non-RAAS inhibitors. Unlike ARBs, ACEIs might help in decreasing the severity and mortality of COVID-19.

Arboviruses are infections caused by arboviruses that may be either symptomatic or asymptomatic, according to individuals' resistance and immune response, which dietary patterns can influence. Thus, this study aimed to investigate the possible association between the occurrence of clinical manifestations of arboviruses and the dietary pattern of the population studied. The study was conducted in a rural population in the metropolitan area of Belém, Pará State, Brazil. The sampling consisted of 95 individuals during a febrile outbreak. Two investigations were conducted: clinical-epidemiological-dietary and laboratory investigation based on blood samples taken for arbovirus analysis. Out of the 95 individuals studied, more than half (57.89%) showed clinical manifestations. Following the laboratory serology (HI and IgM ELISA) analyses, viral isolation in C6/36 cells, and viral genome detection (RT-qPCR), the final diagnosis of the cases was 47.37% Oropouche Fever, 2.11% Oropouche Fever and Chikungunya Fever, and 1.05% Mayaro Fever. Regarding dietary pattern, as for the comparison analyses, statistical significance was observed between dietary pattern and classification regarding the presence of symptoms (p<0.05); after the correspondence analysis, symptomatic cases were more associated with a bad dietary pattern, while asymptomatic cases were more associated with a good dietary pattern.

High oxidative stress in cells due to inflammation process or excessive cell proliferation would produce oxidants or free radicals with biomarkers, one of which is malondialdehyde (MDA). Passion fruit seed’s contain high antioxidant and are expected to decrease the level of cholesterol and MDA. The objective is to identify the effect of passion fruit seed’s ethanol extract in Wistar rats that have been fed with atherogenic feed. The method was preclinical trial (post-test control group design) in rats, by administering passion fruit seed’s ethanol extract for 14 days. This study used 26 male rats aged two months, divided into 5 groups. The result showed significant difference in MDA level which was found in group that was given passion fruit seed extract 10mg/kg BW with positive control group that was given standard feed. Passion fruit seed’s extract showed significant difference in level of triglyceride, which was found in negative control group that was given atherogenic feed with group that was given passion fruit seed’s extract 5mg/kg BW (mean±standard deviation: 1.09±0.30 mg/dL vs 0.77±0.25mg/dL; p=0.048). This study showed that passion fruit seed’s ethanol extract had significant lowering effect in level of MDA, total cholesterol, and triglyceride for 14 days.

Background: Dental education blends theoretical and practical training to prepare students for independent patient care. This study examines the confidence levels of dental students in Umeå regarding independent performance of general dentistry tasks, and whether this confidence changes after clinical training. Methods: Surveys were conducted before and after a summer clinical internship, with s tudents rating their comfort levels on a scale from 0 to 10 for various procedures. Results: Results from 64 initial surveys and 54 follow-up surveys showed no significant difference in confidence before and after the internship. However, confidence levels varied based on whether students had practiced specific tasks during the internship. Students felt least confident in managing acute dental trauma and treating cavities in young children, while they were most confident in tasks like obtaining radiographic surveys and debriding periodontally compromised dentition. Tooth extraction and dental fillings were the most practiced procedures during the internship. Conclusions: The study concludes that the internship between the ninth and tenth semesters does not notably boost students' confidence in specific dental procedures, possibly due to the short duration of the training. Further exploration, including input from clinical supervisors, is suggested to optimize clinical training in dental education.

Chloroquine (CQ) and its derivate hydroxychloroquine (HCQ), the compounds with recognized ability to suppress autophagy, have been tested in experimental works and in clinical trials as adjuvant therapy for the treatment of cancers of different origin to increase the efficacy of cytotoxic agents. Such strategy can be effective to overcome the resistance to standard chemotherapy or anti-angiogenic therapy. This review presents the results of combined application of CQ/HCQ with conventional chemotherapy drugs (doxorubicin, paclitaxel, platinum-based compounds, gemcitabine, tyrosine kinases and PI3K/Akt/mTOR inhibitors, and other agents) for the treatment of different malignancies obtained in experiments on cultured cancer cells and on animal xenograft models, with a few examples of clinical trials. The effects of such approach on viability of cancer cells and tumor growth, as well as autophagy-dependent and independent molecular mechanisms underlying cellular responses of cancer cells to CQ/HCQ are summarized. Although the majority of experimental studies in vitro and in vivo have shown that CQ/HCQ can effectively sensitize the cancer cells to cytotoxic agents and increase the potential of chemotherapy, the results of clinical trials are often inconsistent. Although pharmacological suppression of autophagy remains a promising tool for increasing the efficacy of standard chemotherapy, the development of more specific compounds is required.

DIEP-based breast reconstruction necessitates wide undermining at the abdominal donor-site, creating large wound areas. Flap harvesting is usually conducted using electrosurgical dissection devices. This study sought to compare the clinical outcomes in patients after using the PEAK PlasmaBlade (PPB) versus monopolar electrocautery (MPE). This retrospective cohort study included 128 patients with DIEP-based breast reconstruction. Patient characteristics as well as information on the postoperative course were collected and a comparative evaluation was conducted. The MPE group exhibited significantly (p* = 0.0324) higher abdominal drainage volume (351.11 ± 185.96 ml) compared to the PPB group (279.38 ± 183.38 ml). Subgroup analysis demonstrated that PPB significantly reduced postoperative wound fluid in patients with BMI > 30 kg/m² (p* = 0.0284), without prior neoadjuvant chemotherapy (p** = 0.0041), and among non-smokers (p = 0.0046). Furthermore, postoperative pain was significantly (p**** < 0.0001) lower in the PPB cohort. This study confirms the non-inferiority of the PEAK PlasmaBlade to conventional electrocautery for abdominal flap harvesting. The PPB demonstrated advantages, notably reduced drainage volume and lower postoperative pain levels. Recognizing patient subsets that benefit more from the PPB highlights the importance of personalized device selection based on patient characteristics.

Background: There is a high bureaucratic and administrative burden associated with health care tasks (test requesting, visits scheduling, supporting documents provision) that has historically largely fallen on health care professionals, which is one among the factors contributing to low job satisfaction and lower productivity. Incorporating new professional roles that help to better respond to the needs of both patients and professionals can increase the quality and efficiency of service provision. Objective: To evaluate the impact of the clinical assistant’s introduction in the Sant Joan de Déu Barcelona Children’s Hospital’s pediatric oncology department, in terms of displacement of activity loads carried out by this new professional role and the consequent time freed up for physicians. Methodology: Observational and retrospective study using administrative data based on the analysis of the type of activity performed by clinical assistants and the measurement of the time freed up in favor of the physicians, based on in situ timekeeping, to approximate the potential skill mix productivity increase. Results: Since its implementation in the pediatric oncology department, clinical assistants have performed 13,553 requests (69.93% of the total), representing a total saving of 266.83 hours or 6.67 workweeks of 40 hours. They performed 74.25% of outpatient surgical requests in the oncology department, 87.5% of day hospital requests and 54.13% of total requests in the outpatient consultations area. Conclusion: The introduction of clinical assistants in the oncology department could be efficient to the extent that it displaces a good part of the bureaucratic and administrative tasks previously performed by health care professionals. This delegation allows them to work more closely to the maximum of their competences and the physicians to have more time for higher added value clinical tasks. In terms of efficiency, this role change enables to optimize the clinical process, reducing the cost by 56% compared to the conventional model.

Implementing the methodology of clinical simulation in the nursing degree course is a necessity in the European framework of higher education to acquire competences. The objectives of this research were to evaluate the strategies and techniques used during the simulations, identify the contents learned, and determine which of them are transferred to the nursing practice. We performed an observational, descriptive, and cross-sectional study from the nursing students’ perspective during the 2020-21-year course. On the one hand, our results show that the DASH scale helped us to obtain an internal validity of the simulations obtaining a mean score of 6.61 out of 7. On the other hand, the Ad Hoc scale, based on the competences were acquired in the simulations were transferred to the care practices. In conclusion, it is possible to improve care practices by integrating knowledge through clinical simulations.

Background: One way to demonstrate the existence of nursing is to develop a nursing theory model through nursing research which can ultimately be implemented in nursing practice. RAM is one of the most frequently used models in guiding nursing research. Roy's Adaptation Model (RAM) is one of the most useful conceptual frameworks that guide nursing practice, direct research, and influence education. Theory-guided nursing practice is fundamental in providing the framework for developing superior and quality nursing care.Objectives: This systematic review aims to critically analyze recent studies using RAM as a conceptual framework to identify the effectiveness of this model in guiding nursing research.Methods: A literature search was conducted on five databases, namely SCOPUS, PubMed, ProQuest, ScienceDirect, and SAGEPub. There were no population boundaries and diagnoses involved in the study. The study is a quantitative design focused on publication between 2015-2021. The methodological quality of applying the Cochrane and JBI bias tools. The analysis uses narrative synthesis.Results: 20 studies were found out of 1,315 studies. The research population found is very diverse. The given intervention follows the conceptual framework of RAM. RAM-based interventions effectively overcome the problems experienced by patients and reduce the perceived symptoms and improve the patient's quality of life.Conclusion: The conceptual use of RAM theory in nursing research has been widely reported. RAM-based interventions have a significant impact and have strong evidence-based practice in improving patient health status.

African swine fever (ASF) is one of the most important and devastating viral diseases in wild boar and domestic pigs worldwide. In the absence of vaccines or treatment options, early clinical detection is key and requires sound knowledge of disease characteristics. To provide practitioners and state veterinarians with detailed information, the objective of the present study was to characterize the ASF virus (ASFV) isolate “Belgium 2018/1” in subadult and weaning domestic pigs. To this end, two animal trials were performed. Trial A included eight subadult domestic pigs and trial B five weaner pigs. In general, clinical signs and pathological lesions were in line with previous studies utilizing highly virulent ASF genotype II viruses. However, in trial A, four subadult domestic pigs survived and recovered pointing to an age dependent outcome. The long-term fate of those survivors remains under discussion and would need further investigations.

Designed by a group of ME/CFS researchers and health professionals, the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) has received funding from the European Cooperation is Science and Technology (COST) (https://www.cost.eu/cost-actions/what-are-cost-actions/ ) - COST action 15111 - from 2016 to 2020. The main goal of the Cost Action was to assess the existing fragmented knowledge and experience on health care delivery for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in European countries, and to enhance coordinated research and health care provision in this field. We report on the recommendations for clinical diagnosis, heath services and care for people with ME/CFS in Europe, as prepared by the group of clinicians and researchers from 22 countries and 55 European health professionals and researchers, who have been informed by people with ME/CFS (https://www.cost.eu/actions/CA15111/#tabs|Name:overview).

Background: The commonly known assumption that combinations of several herbs in one formulation can have better efficacy due to additive or synergistic effects has not been systematically studied despite some evidence supporting the synergy concept. Study aim: The study aimed to reveal the molecular interactions in situ of host cells in response to the intervention of BHP and justify the benefits of implementing BHP in clinical practice. Results: This overview provides the results of recent clinical and network pharmacology studies of botanical herbal preparations (BHP) of Rhodiola with other plants, including Ashwagandha, Green Tea, Eleutherococcus, Schisandra, Eleutherococcus, Leuzea, Caffeine, Cordyceps, Gingko, Black Cohosh, saffron, and L-carnosine. Conclusions: The most important finding from network pharmacology studies of BHP was the evidence supporting the synergistic interaction of BHP ingredients, revealing unexpected new pharmacological activities unique and specific to the new BHP. Some studies show the superior efficacy of BHP compared with mono-drugs. At the same time, some a priori-designed combinations can fail, presumably due to antagonistic interactions and crosstalk between molecular targets within molecular networks involved in the cellular and overall response of organisms on the intervention. Network pharmacology studies help predict the results of studies to discover new indications and unpredicted adverse events.

Achieving glycemic control and sustaining functional pancreatic β-cell activity remains an unmet medical need in the treatment of type 2 diabetes mellitus (T2DM). Glucokinase activators (GKAs) constitute a class of anti-diabetic drugs designed to regulate blood sugar levels and enhance β-cell function in patients with diabetes. A significant progression in GKA development is underway to address the limitations of earlier generations. Dorzagliatin, a dual-acting GKA, targets both the liver and pancreas and has successfully completed two Phase III trials, demonstrating favorable results in diabetes treatment. The hepato-selective GKA—TTP399— emerges as a strong contender, displaying clinically noteworthy outcomes with minimal adverse effects. This paper seeks to review the current literature, delve into the mechanisms of action of these new-generation GKAs, and assess their efficacy and safety in treating T2DM based on published pre-clinical studies and clinical trials.

A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, since there is no effective therapy for these diseases so far. The beneficial effects of omega-3 fatty acids are now well established by a plethora of studies through their involvement in multiple biochemical functions, including synthesis of antinflammatory mediators, cell membrane fluidity, intracellular signalling and gene expression. This systematic review will consider epidemiological studies and clinical trials that assessed the impact of supplementation or dietary intake of omega-3 polyunsaturated fatty acids on neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. Indeed, treatment with omega-3 fatty acids, being safe and well tolerated, represent a valuable and biologically plausible tool in the management of neurodegenerative diseases in their early stages.

Immunosenescence refers to age-related alterations of the immune system function affecting both the humoral and cellular arm of immunity. Understanding immunosenescence and its impact on vaccination of older adults is essential since primary vaccine responses in older individuals can fail to generate complete protection, especially vaccines targeting infections with increased incidence among the elderly, such as the respiratory syncytial virus. Here, we review the clinical trials of both candidate and approved vaccines against respiratory syncytial virus (RSV), which include adults aged ≥50 years, with an emphasis on the evaluation of immunogenicity parameters. Currently, there are 10 vaccine candidates and 2 vaccines approved for the prevention of RSV in the older adult population. The number of registered clinical trials for this age group amounts to 32. Our preliminary evaluation of published results and interim analyses of the RSV vaccine clinical trials indicates efficacy in older adult participants, demonstrating immunity levels that closely resemble those of younger adult participants.

Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by progressive accumulation of a rare population of CD5+ B lymphocytes in peripheral blood, bone marrow and lymphoid tissues. CLL exhibits remarkable clinical heterogeneity, with some patients presenting with indolent disease and others progressing rapidly to aggressive CLL. The significant heterogeneity of CLL underscores the importance of identifying novel prognostic markers. Recently, the RAS-related gene RRAS2 has emerged as both a driver oncogene and a potential marker for CLL progression, with higher RRAS2 expression associated with poorer disease prognosis. Although missense somatic mutations in the coding sequence of RRAS2 have not been described in CLL, this study reports the frequent detection of three somatic mutations in the 3' untranslated region (3'UTR) affecting positions +26, +53, and +180 downstream of the stop codon in the mRNA. An inverse relationship was observed between these three somatic mutations and RRAS2 mRNA expression, which correlated with lower blood lymphocytosis and better prognosis. These findings highlight the importance of RRAS2 overexpression in CLL development and prognosis and point to somatic mutations in its 3'UTR as novel mechanistic clues. Our results may contribute to the development of targeted therapeutic strategies and improved risk stratification for CLL patients.

1. Background and Objective: Spontaneous Intracranial Hemorrhage (ICH) is a catastrophic medical condition associated with significant morbidity and mortality. As the accumulation of unbound iron following ICH contributes to secondary brain injury, deferoxamine, an approved chelation drug, has become the center of attention. At the same time, its therapeutic remains a matter of dispute. This double-blinded Randomized Controlled Trial (RCT) aims to investigate the therapeutic potential of deferoxamine in neurological and radiological aspects. 2. Methods and Materials: The study enrolled 42 participants diagnosed with spontaneous ICH and confirmed by CT scan, randomly assigning them to either the deferoxamine treatment group or the placebo control group. While the control group received the routine treatment plus a placebo, the treatment group received routine treatment conjugated with 7.5 mg/kg of deferoxamine per hour intravenously over the first three days. The study compared hematoma and edema volume, GCS score, and mortality rates between the two groups. Our study employed rigorous randomization and blinding procedures to ensure unbiased results. 3. Results: There was a significant (p<0.05) improvement in patients' GCS up until the fourth day, but no significant difference was noted afterward. In addition, the volume of both edema and hematoma was significantly lower in the intervention group, as well as the length of stay, intubation requirement, and mortality. 4. Discussion: Deferoxamine administration can, at least in a short timeframe, improve neurological and radiological parameters.

Abstract. The COVID-19 has turned in to a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in R&D by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are ‘rate-limiting’ and ‘time-consuming’, many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human ‘challenge experiments’ to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying ‘Quick fix’ and ‘short cuts’ can lead to errors with disastrous consequences.

Blood-based biomarkers for early detection of recurrence have a significant clinical impact on the improved management of breast cancer patients, as cancer recurrence results in poor prognosis. This study aimed to investigate if the measurement of blood endocan in breast cancer patients with high ESM1 expression could be an effective tool to detect postoperative recurrence compared with existing tumor markers. Blood was collected before and after the tumor resection from the mouse models of breast cancer, and endocan levels were measured while visualizing metastatic recurrence with noninvasive luminescence imaging. In clinical settings, blood was withdrawn from 16 breast cancer patients before and after the tumor resection, and the effect of lumpectomy on blood endocan level was evaluated. Additionally, the blood endocan from 20 patients diagnosed with postoperative recurrence was measured, and their positivity rate for endocan was compared with that for serum carcinoembryonic antigen (CEA) or cancer antigen 15-3 (CA15-3). Our preclinical and clinical experiments revealed that blood endocan levels reflected tumor burden. Furthermore, over 60% of patients suffering from postoperative recurrence who tested negative for CEA or CA15-3 were positive for endocan. Our results support the clinical significance of endocan in breast cancer patients for detecting breast cancer recurrence.

This review explores the complex interrelationships between emotion, attention, and behavior, drawing upon empirical evidence from psychological, neuroscientific, and clinical studies. It delves into the neural mechanisms that underlie these interactions, with a focus on key brain regions such as the prefrontal cortex and amygdala. Clinical cases involving stroke and attention-deficit/hyperactivity disorder (ADHD) are examined to illustrate the real-world implications of these cognitive interactions. The review also discusses the impact of effective emotion regulation strategies and the role of attention as a cognitive mechanism that influences both emotion and behavior. Neuroimaging studies, particularly functional MRI, are highlighted for their role in providing a deeper understanding of these intricate relationships. The review concludes by emphasizing the importance of this triadic relationship in adaptive functioning and its broader implications for mental health, interpersonal relationships, and quality of life.

Post operative recurrence (POR) is the rule in patients with Crohn’s disease (CD), mitigated with prophylactic therapy. The evidence for therapeutic choice and timing of intervention is lacking. We aimed to compare rates of POR in patients treated early with prophylactic 6-mercaptopurine (6-MP) or adalimumab. We conducted a prospective single center randomized open label clinical study, in which patients in surgical remission following their first ileocecectomy were randomized to receive early treatment with 6-MP or adalimumab. Patients were followed up clinically every 3 months and underwent endoscopy at weeks 32 and 58 post-operatively. The primary endpoint was endoscopic recurrence (ePOR) at 1 year (week 58), defined as a Rutgeerts score≥i2. We enrolled 35 patients (25 males, mean age 35±1.4 years, median disease duration 5±6.1 years) following ileocecectomy. Of these, 7(20%) were current smokers and 9(26%) biologics experienced. Patients allocated to adalimumab had significantly less ePOR than patients treated with 6MP at week 32 (21% vs 69%, p=0.004) and 58 (47% vs 75%), (p=0.03, HR=0.39, 95% CI=0.16-0.93). POR was associated with increased diameter of the resected small bowel surgical specimen, lower baseline body mass index (BMI), increased week 18 fecal calprotectin and serum alanine aminotransferase and decreased week 18 hemoglobin level. Adalimumab is more effective than 6-MP in preventing ePOR. Increased operative small bowel diameter and lower post-operative BMI were associated with ePOR. Eighteen weeks serum hemoglobin and ALT, and fecal calprotectin levels were predictive of endoscopic disease recurrence. (ClinicalTrials.gov ID NCT01629628).

The emergence of M. tuberculosis strains resistant to Isoniazid (INH) and Rifampicin (RIF), the two most potent drugs of first-line anti-TB therapy is termed multidrug drug-resistant TB (MDR-TB). Multidrug-resistant tuberculosis has been a serious medical and epidemic problem all over the world. We present here a series of clinical cases consist of two patients diagnosed with isoniazid resistant tuberculosis. Histopathological examination supports the diagnosis of tuberculous granulomas. And the pathology molecular examination revealed the presence of Isoniazid-resistant Mycobacterium tuberculosis1,2 via the following mutation c.947G&gt;A; p.Gly316Asp. Isoniazid-resistance is associated with mutations in the furA-katG and fabG1-inhA operons, as well as mutations in the ahpC gene. 64% of the isoniazid-resistance phenotypes were associated with the katG315 mutation worldwide. The second most common mutation is inhA-15, and it has been reported in 19% of the Isoniazid-resistant isolates. The significant association between the two mutations, inhA c-15 and katG 315 respectively, and the high-level resistance is of interest in the interpretation of current and future molecular diagnostic testing, as an early prediction of the level of Isoniazid-resistance is essential to decide the benefit of high-dose Isoniazid use.

ChatGPT is gaining widespread acceptance for its ability to generate natural language sentences in response to various inputs and is expected to become a supplementary tool for diagnosing and determining treatment policies in clinical settings. ChatGPT was used to evaluate its ability to perform clinical inference and accuracy in answering questions on the 117th Japanese National Medical Licensing Examination held in February 2023. The exam questions were manually inputted into ChatGPT's window, and the accuracy of ChatGPT's responses was determined based on answers provided by a preparatory school. ChatGPT provided answers for 389 out of 400 questions, and its overall correct answer rate was 55.0%. The correct answer rate for 5-choice-1, 5-choice-2, and 5-choice-3 were 57.8%, 42.9%, and 41.2%, respectively. The highest correct answer rate was for the compulsory exam (67.0%), followed by the specific knowledge exam (54.1%) and the cross category exam (47.9%). The correct answer rate for non-image questions was 56.2% and for image questions, it was 51.5%. The study suggests that ChatGPT has potential to support healthcare professionals in clinical decision-making in Japanese clinical settings, but caution should be exercised in interpreting and using the answers generated by ChatGPT due to room for improvement in performance.

The World Health Organization has identified antimicrobial resistance as a public health emergency and developed a global priority pathogens list of antibiotic-resistant bacteria that can be summarized in the acronym ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales species), reminding us of their ability to escape the effect of antibacterial drugs. We previously tested new heteroaryl-ethylene compounds in order to define their spectrum of activity and antibacterial capability. Now, we focus our attention on PB4, a compound with promising MIC and MBC values in all conditions tested. In the present study, we evaluate the activity of PB4 on selected samples of ESKAPE isolates from nosocomial infections: 14 S. aureus, 6 E. faecalis, 7 E. faecium, 12 E. coli and 14 A. baumanii. Furthermore, an ATCC control strain was selected for all species tested. MICs were performed according to the standard method, with some modifications. PB4 MIC values were within very low ranges regardless of bacterial species and resistance profiles: from 0,12 to 2 mg/L for S. aureus, E. faecalis, E. faecium and A. baumannii. For E. coli, the MIC values obtained were slightly higher (4-64 mg/L), butstill promising. The PB4 heteroaryl-ethylenic compound was able to counteract the bacterial growth of both high-priority Gram-positive and Gram-negative clinical strains. In the future, it would be interesting to evaluate the activity of PB4 in animal models to test for its toxicity.

COVID-19 was identified in Wuhan, China in in December 2019, and rapidly spread worldwide, being declared global pandemic one month later on 30 January 2020. Since its emergence, COVID-19 has raised global concerns associated with drastic measures that were never adopted in any previous outbreak, to contain the situation as early as possible. The 2019 novel corona virus (2019-nCoV) or SARS-CoV-2 is the causative agent of COVID-19. 2019-nCoV genetic sequence was rapidly identified within few days since the first reported cases and RT-PCR kits became available for COVID-19 diagnosis. However, RT-PCR diagnosis carries a risk of false-negative results, therefore additional serologic test are needed. The most important approach in the battle against COVID-19 is rapid diagnosis of suspicious cases, timely therapeutic intervention and isolation to avoid community spread. In this review, we summarize the clinical scenario that raises suspicion of COVID-19 and available laboratory diagnostics.

Aim: The overall aim of the study was to assess the reasons and experiences of participants involved in Antibody Mediated Prevention (AMP) HIV prevention clinical trial at University of North Carolina (UNC) Project, Lilongwe, Malawi. We determined the participants’ reasons for participating in HIV Prevention clinical trials; and the experiences of participants in HIV Prevention clinical trials. Methods: We adopted the qualitative cross-sectional study method. Data were collected using in-depth interviews (IDIs). Purposive sampling was used to select 12 study participants who consented to take part in the study. All participants were the ones taking part in the AMP HIV prevention study at the UNC Project. Data analysis was done concurrently with data collection using content analysis. Results: Individuals were motivated to participate in HIV research due to a range of perceived benefits. These included personal, health, and financial benefits. Participants' research experiences and their continued participation in HIV research were influenced by the research clinic context and the nature of their interactions with research staff. Conclusion: When the clinical trial study participants’ expectations are met through what they experience in the study, the chances of them adhering to the study visits and procedures are high. Even for those who did not have any expectations prior to the study, feeling welcomed and being able to open up to the study staff encouraged their continued participation. In the end, this outweighed the negative comments made by the people in their communities or their friends

Surgical neurolysis is a procedure designed to liberate an injured nerve from scar tissue or adjacent structure, thereby facilitating nerve regeneration in cases of brachial plexus neuropathy (BPN). This study presents a case series of patients diagnosed with BPN who underwent surgical neurolysis. The primary focus was on the clinical assessment of recovery using the British Medical Research Council motor grading scale (BMRC). Additionally, a comprehensive literature review was conducted to analyze motor recovery outcomes related to surgical neurolysis for BPN. 18 patients with BPN who underwent surgical neurolysis where included. The results experienced a notable increase of 58% in muscle strength as assessed by the BMRC. The average preoperative state of 2.17±1.15 improved significantly to a postoperative condition of 3.44±1.34 (p = 0.003, d= 0.913) The systematic review identified 2298 articles which were selected for qualitative analysis, demonstrated that surgical neurolysis was associated with favorable motor recovery outcomes in 75.82% of the patients. Both the case series and the literature review reveal significant motor recovery following surgical neurolysis. It is crucial to conduct well-designed, adequately powered, randomized, and blinded clinical trials. Such studies will provide robust evidence to support or refute the utility of this approach in motor recovery.

Shoulder pain is a serious clinical disease frequently related to absence from work. It’s characterized by pain and stiffness probably connected to the presence of an inflammatory substrate involving gleno-humeral capsule and collagen tissues. A physioterapy programme has shown to be effective for the conservative treatment of this disorder. Our aim is to assess if a manual treatment directed to fascial tissues could get better improvement regarding pain, strength, mobility and function. 94 healthcare workers with recurrent shoulder pain were recruited and then randomized in two groups: the control group (CG) underwent a physiotherapy programme; the study group (SG) underwent to 3 sessions of physiotherapy and to 2 session of Fascial Manipulation (FM) technique. At the end of the treatment phase, both groups improved every outcome. Despite few statistical differences between groups, at the follow up visit a greater percentage of subjects in SG overcame the minimal clinical important difference (MCID) in every outcome. We conclude that FM is effective for treatment of shoulder pain and further studies should better assess how to manage this treatment to get better results.

Clinical trials often involve new substances characterized or developed for a specific pathology or class of pathologies. At other times, a clinical trial is observational; in other words, a known sub-stance has a range of effects on a given cohort of subjects. The types of trials are different and complex, and often, young clinical novice and the inexperienced researchers may struggle to evaluate how to proceed correctly. In this paper, we aim to create a mini-guide for beginners in clinical trials and provide elements for designing a clinical trial. Our intention is to highlight where to find the materials and how to adapt, even in the absence of sponsors, so that even the most inexperienced and under-resourced researcher can gain an understqanding of the complexi-ty of the process andaddress it appropriately. We do not claim to be exhaustive or cover all ele-ments, but rather, we aim to create a checklist. With this approach, starting discussioms about the experimental phases of the drug and concluding with the clinical trial, we aim to assist those facing this challenging "world."

Validation and verification are the critical requirements in the knowledge acquisition method for the clinical decision support system (CDSS). After acquiring the medical knowledge from diverse sources, the rigorous validation and formal verification process are required before creating the final knowledge model. Previously, we have proposed a hybrid knowledge acquisition method for acquiring medical knowledge from clinical practice guidelines (CPGs) and patient data in the Smart CDSS for treatment of oral cavity cancer. The final knowledge model was created by combining knowledge models obtained from CPGs and patient data after passing through a rigorous validation process. However, detailed analysis shows that due to lack of formal verification process, it involves various inconsistencies in knowledge relevant to the formalism of knowledge, conformance to CPGs, quality of knowledge, and complexities of knowledge acquisition artifacts. Therefore, it is required to enhance a hybrid knowledge acquisition method that thwarts the inconsistencies using formal verification. This paper presents the verification process using the Z formal method and its outcome as an enhanced acquisition method – known as the refined knowledge acquisition (ReKA) method. The ReKA method adopted verification method and explored the mechanism of theorem proving using the Z notation. It enables to identify inconsistencies in the validation process used for hybrid knowledge acquisition. Additionally, it refines the hybrid knowledge acquisition method by discovering the missing steps in the current validation process at the acquisition stage. Consequently, ReKA adds a set of nine additional criteria to be used to have a final valid refined clinical knowledge model. The criteria ensure the validity of final knowledge model concerning formalism of knowledge, conformance to GPGs, quality of the knowledge, usage of stringent conditions and treatment plans, and inconsistencies possibly resulting from the complexities. Evaluation, using four medical knowledge acquisition scenarios, shows that newly added knowledge in CDSS due to the addition of criteria by ReKA method always produces a valid knowledge model. The final knowledge model was also evaluated with 1229 oral cavity patient cases, which outperformed with an accuracy of 72.57\% compared to a similar approach with an accuracy of 69.7\%. Furthermore, ReKA method identified a set of decision paths (about 47.8%) in the existing approach, which results in a final knowledge model with low quality, non-conformed from standard CPGs. In conclusion, ReKA is formally proved method which always yields valid knowledge model having high quality, supporting local practices, and influenced from standard guidelines.

Over a year into the COVID-19 pandemic, there is growing evidence that SARS-CoV-2 infections among dogs are more common than previously thought. In this study, the prevalence of SARS-CoV-2 antibodies was investigated in two dog population. The first group was comprised of 1069 dogs admitted to the Veterinary Teaching Hospital for any given reason. The second group included dogs that shared households with confirmed COVID-19 cases in humans. This study group numbered 78 dogs. In COVID-19 infected households, 43.9% tested ELISA positive, and neutralisation antibodies were detected in 25.64% of dogs. Those data are comparable with the secondary attack rate in the human population. With 14.69% of dogs in the general population testing ELISA positive, there was a surge of SARS-CoV-2 infections within the dog population amid the second wave of the pandemic. Noticeably seroprevalence of SARS-CoV-2 in the dog and the human population did not differ at the end of the study period. Male sex, breed and age were identified as significant risk factors. This study gives strong evidence that while acute dog infections are mostly asymptomatic, they can pose a significant risk to dog health. Seropositive dogs had a 1.97 times greater risk for developing central nervous symptoms.

Protein phosphatase 2A (PP2A) is a ubiquitous serine/threonine phosphatase implicated in a wide variety of regulatory cellular functions. PP2A is abundant in the mammalian nervous system and dysregulation of its cellular functions are associated with myriad neurodegenerative disorders. Additionally, PP2A has oncologic implications, recently garnering attention and emerging as a therapeutic target because of the antitumor effects of a potent PP2A inhibitor, LB100. LB100 abrogation of PP2A is believed to exert its inhibitory effects on tumor progression through cellular chemo- and radio-sensitization to adjuvant agents. An updated and unifying review of PP2A biology and inhibition with LB100 as a therapeutic strategy for targeting cancers of the nervous system is needed, as other reviews have mainly covered broader applications of LB100. In this review, we discuss the role of PP2A in normal cells and tumor cells of the nervous system. Further, we summarize current evidence regarding the therapeutic potential of LB100 for treating solid tumors of the nervous system.

Objectives: The aim of our current study was to analyze whether the use of important measures of methodological quality and reporting of randomized clinical trials published in the field of cardiovascular disease research have changed over time. Further aim was to investigate whether there was an improvement over time in the ability of these trials to provide a good estimate of the true intervention effect. Methods We conducted two searches in the Cochrane Central Register of Controlled Trials (CENTAL) database to identify cardiovascular clinical research trials published in either 2012 or 2017. Randomized clinical trials (RCTs) trials in cardiovascular disease research with adult participants were eligible to be included. We randomly selected 250 RCTs for both publication year 2012 and 2017. Trial characteristics, data on measures of methodological quality and reporting were extracted and risk of bias for each trial was assessed. Results As compared to 2012 in 2017 there were significant improvements in the reporting of the presence of a data monitoring committee (42.0% in 2017 compared to 34.4% in 2012), and a positive tendency of registering cardiovascular disease research RCTs in clinical trial registries (83.6% in 2017 compared to 72.0% in 2012). On the other hand, we also observed that significantly fewer RCTs reported sample size calculation (60.4% in 2017 compared to 98.4% in 2012) in 2017 as compared to 2012. RCTs in 2017 were more likely to have low overall risk of bias ( RoB ) than in 2012 (29.2% in 2017compared to 21.2% in 2012). Conclusion: As compared to 2012 in 2017 there were significant improvement in some, but not all the important measures of methodological quality. Although more trials in the field of cardiovascular disease research had a lower overall RoB in 2017, the improvement over time was not consistently perceived in all RoB domains.

Lung cancer, globally recognized as the leading cause of cancer-related mortality, presents a pressing need for innovative treatment strategies. Increasing evidence points towards the potential of monoamine oxidase (MAO) inhibitors in modulating cancer progression, primarily due to their role in regulating cellular metabolism and apoptotic pathways. This extraordinary study delves into the multifaceted therapeutic implications of MAO inhibitors in lung cancer management, elucidating their ability to pave the way for clinical advancement via novel targets and pathways. Capitalizing on recent advances in molecular biology, this research explores the molecular mechanisms underlying the anticancer actions of MAO inhibitors. By examining their impact on cell proliferation, migration, invasion, and apoptosis in lung cancer cell lines, we provide insight into the intricate signaling pathways and biochemical processes modulated by these compounds. The study also investigates the synergistic effects of MAO inhibitors in combination with established chemotherapeutic agents, elucidating their potential to enhance treatment efficacy and reduce cytotoxicity. Furthermore, we delve into the implications of MAO inhibitors on the tumor microenvironment, evaluating their influence on angiogenesis, immune regulation, and the epithelial-mesenchymal transition. This comprehensive analysis enables the identification of novel molecular targets, which hold promise for the development of advanced therapeutics tailored for specific lung cancer subtypes. To substantiate our findings, in this review, we thoroughly analyze the existing literature using state-of-the-art bioinformatics tools." in vivo orthotopic lung cancer models, and clinical patient cohorts. This robust and multidisciplinary approach permits the generation of clinical evidence supporting the integration of MAO inhibitors in lung cancer management. Conclusion: This ground-breaking study establishes the therapeutic potential of monoamine oxidase inhibitors in lung cancer management by unearthing novel pathways and targets for clinical advancement. The outcomes open doors for the development of innovative treatment strategies and inspire continued research efforts to combat the global burden of lung cancer.

This study aimed to explore how Indonesian clinical psychologists (CPs) address aspects of spirituality and religion (SR), particularly their attitudes towards and experience of it, on the mental health context. Semi-structured interviews were conducted with 43 CPs in public health centres in Yogyakarta Province, Indonesia. Data were anyalsed using deductive thematic analysis and they generated ten sub-themes which were merged into three central themes. The first theme was experiences related to SR, particularly in Indonesian sociocultural context. The second theme concentrated on participants’ clinical experience related to SR integration into clinical practice. The last theme highlighted the effort made by participants to create holistic mental health services. The originality of this study was represented by the interview quote in the title, “Doing my profession is also part of worship”. It was found that SR is part of culture and belief among Indonesian people, including CPs and mental health treatment clients. In summary, participants genuinely acknowledged that they were not able to completely detach SR from their professional practice. However, participants also pointed out that they were different with spiritual-religious healers (SRHs) and favourably welcomed future collaboration with credible SRHs. This positive attitude embodied a holistic care approach that recognises the diverse biopsycho-social-spiritual needs of clients. Therefore, professional organisations and psychology faculties should establish regulations and education of SR in psychology curricula and conventional psychotherapy to achieve this holistic mental health services in Indonesia.

This study was aimed to examine the recent trends of antibiotic resistance (AR) prevalence in Staphylococcus aureus isolated from milk of animals with clinical mastitis in areas of the Abruzzo and Molise regions in central Italy. Fifty-four S. aureus isolates could be obtained from routine testing for clinical mastitis agents carried out in the author institution in years 2021 and 2022. These were analyzed for phenotypic resistance to eight antibiotics recommended for testing by European norms and belonging to the antibiotic classes used for mastitis treatment in milk producing animals. Moreover, the presence of 14 transferable genetic determinants encoding resistance to the same antibiotics was analyzed by qPCR tests developed in this study. Phenotypic resistance to non-β-lactams was infrequent, with only one 2022 isolate resistant to clindamycin. However, low level resistance to the β-lactam cefoxitin was observed in 59.2% isolates in both years making these isolates classifiable as methicillin resistant. The AR genotypes detected were blaZ gene (50% 2021 isolates and 44.4% 2022 isolates), ermC/T- aphA3-blaZ (one 2021 isolate), ant6-ermC/T-aphA3-blaZ (one 2021 isolate), ermB-blaZ (one 2022 isolate) and mecA-mph (one 2022 isolate). An interview to the veterinarians who conferred the samples, regarding antimicrobials prescribed for mastitis treatment and criteria of usage, indicated a possible causal relation with the AR test results. The low prevalence of AR genotypes, not increasing in time, most probably reflecting the reported management of antibiotic therapies in farms. However, the frequently observed cefoxitin resistance needs to be explained genotypically, further monitored and limited by modifying antibiotic usage practices. The identification of a mecA positive isolate in 2022 suggests to investigate further if this genotype is emerging locally.

Chromosomal instability (CIN), defined by variations in the number or structure of chromosomes from cell to cell, is recognized as a distinctive characteristic of cancer, associated with the ability of tumors to adapt to challenging environments. CIN has been recognized as a source of genetic variation that leads to clonal heterogeneity (CH). Recent findings suggest a potential association between CIN and CH with the prognosis of BC patients, particularly in tumors expressing the epidermal growth factor receptor 2 (HER2+). In fact, information on the role of CIN in other BC subtypes, including luminal B BC, is limited. Additionally, it remains unknown whether CIN in luminal B BC tumors, above a specific threshold, could have a detrimental effect on the growth of human tumors, or if low or intermediate CIN levels could be linked to a more favorable BC patient prognosis when contrasted with elevated levels. Clarifying these relationships could have a substantial impact on risk stratification and the development of future therapeutic strategies aimed at targeting CIN in BC. This study aimed to assess CIN and CH in tumor tissue samples from ten patients with luminal B BC, and compared them with established clinicopathological parameters. The results of our study show that luminal B BC patients exhibit intermediate CIN and stable aneuploidy, both of which correlated with lymphovascular invasion. These findings suggest that evaluating CIN, CH and aneuploidy could improve risk stratification, the prediction of clinical outcomes and future therapeutic approaches in luminal B BC patients.

Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccines in pipeline to prevent it but a systematic review on immunogenicity and safety of vaccine is lacking. Methods: This systematic review of RSV vaccine clinical trials was undertaken using 4 databases. Searches were conducted using both controlled vocabulary terms such as ‘Respiratory Syncytial Virus, Human’, ‘Respiratory Syncytial Virus Infections’, ‘Respiratory Syncytial Virus Vaccines’, ‘Immunization’, ‘Immunization Programs’ and ‘Vaccines’ and corresponding text word terms. The searches for published papers were limited to clinical trials published from January 2000 to August 6th, 2018. RSV infection case was defined as RSV associated medically attended acute respiratory illness (MAARI) or RSV infection by serologically-confirmed test (Western Blot) during the RSV surveillance period. We calculated the relative risk of each vaccine trial with RSV infection case. Results: Of 4395 publications, 24 were included and data were extracted covering 4 major types of RSV vaccine candidates, these being live-attenuated/chimeric (n=9), recombinant-vector (n=10), subunit (n=1) and nanoparticle vaccines (n=4). For RSV infection cases, 7 trials were involved and none of them showed a vaccine-related increased MAARI during RSV surveillance season. Conclusion: LID ∆M2-2, MEDI M2-2, and RSVcps2 (live-attenuated) were considered the most promising vaccine candidates in infant and children. In the elderly, a nanoparticle F vaccine candidate was considered as a potential effective vaccine. Although no promising vaccine was identified from pregnant-women test, RSV F-024 subunit vaccine candidate and an RSV F nanoparticle vaccine showed encouraging results in healthy non-pregnant women.

Meta-analysis of plant sterol supplement studies suggests an 8% lowering of LDL cholesterol for 2 to 2.5g/day of plant sterols. Cereal foods have been rarely tested and one study showed a lower LDL lowering of 5.4% with 1.6g of plant sterol in breakfast cereal. We aimed to test a breakfast wheat biscuit with 2g of plant sterols in a single serve of two wholegrain wheat breakfast cereal biscuits. Fifty volunteers with a total cholesterol of >5.5mmol/L were recruited for a randomised crossover study with two 4-week periods with no washout of which 45 successfully completed the study. After exclusion of four outliers the difference in LDL cholesterol between standard wholegrain wheat breakfast cereal biscuit and plant sterol-enriched wholegrain wheat breakfast cereal biscuit was 0.23 mmol/L or 5.6% (P=0.001) with a 95% confidence interval of 2.4-8.9%. Men and daily cereal consumers had greater responses 9.8% vs 3.6% and 7.2% vs 3.8% respectively (P<0.05). The LDL lowering effect of 2g of plant sterol enriched from one serve of wholegrain wheat breakfast cereal biscuit was not significantly different from other food products delivering 2-2.5g of plant sterols daily. Regular cereal consumers have a better response.

Steroid analysis is important in the clinical assessment of endocrine function in health and disease. Although tandem mass spectrometry methods coupled with chromatographic separation are considered the gold standard analytical technique in this setting, enabling profiling of multiple steroids in a single sample, sample processing can be labour-intensive. Here we present a simple, efficient automated 96-well Supported Liquid Extraction method with dichloromethane/isopropanol as organic solvent, carried out on a Extrahera automated sample handler (Biotage), which completes sample preparation of 80 plasma samples (200µL) in 90 minutes. Compounds were separated on a Kinetex C18 column (150x3mm;2.6um) using a mobile phase of methanol and water (0.1% formic acid). The run time was 16 minutes on a Nexera uHPLC system (Shimadzu) with a QTrap 6500+ linear ion trap mass spectrometer (AB Sciex). Precisions ranged 8.1 to 18.1% RSD, bias -10.1-5.8%, and extraction recoveries 73.5-111.9%. LOQs ranged between 0.025–0.500 ng/mL.

Objective: To examine the burnout syndrome among the healthcare personnel in Puerto Rico during the COVID-19 pandemic. Methods: Descriptive study that pursues to understand burnout syndrome in the clinical personnel in Puerto Rico. The Maslach Burnout Inventory (MBI) was sent via email to healthcare professionals around the island. Furthermore, open questions were asked to the participants. Results: The overall burnout level on the clinical personnel was found to be moderate. Nonetheless, in physicians, 12.1% had severe burnout levels compared to a 13.1% score in nurses. Additionally, 92.4% of physicians and 100% of nurses had moderate to severe burnout. In the three subscales, nurses scored high levels in all of them, and physicians were high in Emotional Exhaustion and moderate level in Depersonalization and Personal Accomplishment at Work. There were high levels of burnout syndrome of the clinical personnel in Puerto Rico. Conclusion: Since the beginning of the COVID-19 pandemic, over 90% of healthcare professionals in Puerto Rico have been working with moderate to severe burnout syndrome, being the nurses the most affected. Key Words: Burnout syndrome, MBI, Clinical personnel, COVID-19, SARS-CoV-2

Approximately 6% of adults worldwide suffer from peripheral artery disease (PAD) primarily caused by atherosclerosis of lower limb arteries. Despite optimal medicine and revascularization, many PAD patients remain symptomatic and progress to critical limb ischemia (CLI) and risk major amputation. Delivery of pro-angiogenic factors as proteins or DNA, stem or progenitor cells confers vascular regeneration and functional recovery in animal models of CLI, but the effects are not well replicated in patients and no pro-angiogenic biopharmacological procedures are approved in the US. The reasons are unclear, but animal models that do not represent clinical PAD/CLI are implicated. Consequently, it is unclear whether the obstacles to clinical success lie in the toxic biochemical milieu of human CLI, or in procedures that were optimized by inappropriate models. The question is significant because the former case requires abandonment of current strategies, while the latter encourages continued optimization. These issues are discussed in the context of relevant preclinical and clinical data, and it is concluded that preclinical mouse models that include age and atherosclerosis as the only comorbidities that are consistently present and active in clinical trial patients are essential to predict clinical success. Of the reviewed materials, no biopharmacological procedure that failed in clinical trials had been tested in animal models that included advanced age and atherosclerosis relevant to PAD/CLI.

Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay, however almost all patients will eventually transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC generally develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.

Deep behavioral covariates (DBCs) introduced in this perspective form a new class of covariates that have the potential to enhance the performance of predictive models and improve analytics in clinical decision support applications. DBCs can measure how engaged a patient tends to be and how he or she tends to respond to events, and they may be highly predictive of the patient’s outcomes for a planned treatment. DBCs may potentially serve as a standard to measure patient engagement and activation and may form highly efficient mechanisms for improving patient outcomes.

Aging is the results of several complex and multifactorial processes, where several agents contribute to increase intrinsic vulnerability and susceptibility to age-related diseases. The hallmarks of aging are a set of biological mechanisms, finely regulated and strictly interconnected, initiating or contributing to biological changes anticipating several age-related diseases. The complex network of cellular and intercellular connections between the hallmarks might represent a possible target for the research of agents with pleiotropic affects. Vitamin D (VitD) is known to have positive impact not only on muscle and bone health, but also on several extra-skeletal districts, due to the widespread presence of VDRs (VDR). VitD and VDR could be molecules potentially targeting the hallmark of aging network. To date, evidence about the potential effect of VitD on the hallmark of aging is scarce in humans and mainly based on preclinical models. Although underpowered and heterogeneous, in-human studies seems to confirm the modulatory effect of VitD on some hallmarks aging and diseases. However, more investigations are needed to clarify the pleiotropic effects of VitD and its impact on the hallmark of aging, hopefully highlighting the courses for translational applications and potential clinical conclusions.

Background: Takayasu’s arteritis is a rare type of vasculitis, with severe complications like stroke, ischemic heart disease, pulmonary hypertension, secondary hypertension, aneurysms. Diagnosis is conducted by clinical and angiographic criteria. Treatment is medical and surgical, but unfortunately, the outcome is reserved. Case presentation: A 34- year- old Caucasian women had an ischemic stroke (2009). She was diagnosed with Takayasu’s arteritis and she received treatment with methotrexate, prednisolone, antiplatelet agents, with a mild improvement of clinical state. After 5 years (2014) she associated ascending aorta aneurysm, pulmonary hypertension, mild aortic regurgitation. The surgical treatment solved both ascending aorta aneurysm and left carotid artery stenosis (ultrasound in 2009 and computed tomography angiogram in 2014). Morphopathology revealed typical appearance for Takayasu’s arteritis. Tumor necrosis factor inhibitors (TNF-inhibitors) were associated to methotrexate. At 48 years (2023) she developed coronary heart disease (angina, electrocardiogram); echocardiography revealed severe pulmonary hypertension; angiography described normal coronary arteries, abdominal aorta pseudoaneurysm and arterial-venous fistula, with origin in right coronary artery and drainage on medium pulmonary artery. The patient refused surgical/ interventional treatment; she received again TNF- inhibitors, methotrexate, antiplatelet agents, statins. Conclusions: This case report presents us a severe form of Takayasu’s arteritis. We consider that morphopathology had a great importance in revealing to clinicians the typical appearance and the stadialization of inflammatory arterial process: acute or chronic. The verdict of morphopathologist was chronic phase, with acute relapses, so we decided that immunosuppressive treatment was still necessary.

Effective healthcare relies on accurate and timely diagnosis; however, obtaining large amounts of training data while maintaining patient privacy remains challenging. This study introduces a novel approach utilizing federated learning (FL) and a cross-device multi-modal model for clin-ical event classification using vital signs data. Our architecture leverages FL to train machine learning models, including Random Forest, AdaBoost, and SGD ensemble model, on vital signs data from a diverse clientele at a Boston hospital (MIMIC-IV dataset). The FL structure preserves patient privacy by training directly on each client's device without transferring sensitive data. The study demonstrates the potential of FL in privacy-preserving clinical event classification, achieving an impressive accuracy of 98.9%. These findings underscore the significance of FL and cross-device ensemble technology in healthcare applications, enabling the analysis of large amounts of sensitive patient data while safeguarding privacy.

Immune checkpoint inhibitors (ICIs) are a class of drug that produces durable and sustained anti-tumour responses in a wide variety of malignancies. The exponential rise in their use has been mirrored by a rise in immune-related adverse events (irAEs). Knowledge of such toxicities, as well as effective management algorithms for these toxicities, is essential to optimize clinical efficacy and safety. Currently, the guidelines for management of the irAEs are based largely on retrospective studies and case series. In this article, we review the current landscape of clinical trials investigating the management of irAEs with an aim to develop standardized, randomized controlled trial-based management algorithms for ICI-related toxicities.

The virtually complete loss of intestinal worms, known as helminths, from Western society has resulted in elimination of a range of helminth-induced morbidities. Unfortunately, that loss has also led to inflammation-associated deficiencies in immune function, ultimately contributing to widespread pandemics of allergies, autoimmunity, and neuropsychiatric disorders. Several socio-medical studies have examined the effects of intentional reworming, or self-treatment with helminths, on a variety of inflammation-related disorders. In this study, the latest results from ongoing socio-medical studies are described. The results point toward two important factors that appear to be overlooked in some if not most clinical trials. Specifically, (a) the method of preparation of the helminth can have a profound effect on its therapeutic efficacy, and (b) variation between individuals in the effective therapeutic dosage apparently covers a 10-fold range, regardless of the helminth used. These results highlight current limits in our understanding of the biology of both hosts and helminths, and suggest that information from self-treatment may be critical for clinical evaluation of the benefits and limits of helminth therapy.

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1,007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR industry may be a robust response to success and failure of competitor products.

Concomitant neuropathological hallmarks of Alzheimer’s Disease (AD) are common in the brains of people with Parkinson’s disease (PD). Furthermore, AD biomarkers are associated with cognitive decline and dementia in PD patients during life. Here, we highlight the considerable overlap between AD and PD, emphasizing neuropathological, biomarker, and mechanistic studies. We suggest that precision medicine approaches may successfully identify PD patients most likely to develop concomitant AD. The ability to identify PD patients at high risk for future concomitant AD in turn provides an ideal cohort for trials of AD-directed therapies in PD patients, aimed at delaying or preventing cognitive symptoms.

Background: The treatment plan of prosthetic restorations supported by dental implants require comprehensive scientific knowledge to deliver prostheses with good prognosis, even before the implant insertion. This review aims to analyze the main prosthetic determinants of the prognosis of implant-supported prostheses. Methods: A systematic review of the literature was conducted with a PICO question: "For partially or complete edentulous subjects treated with implant-supported prostheses, which prosthetic factors could affect clinical outcomes?". A literature search was performed electronically in PubMed (MEDLINE), Scopus and Cochrane Library with the following equation [PROGNOS* OR RISK] FACTOR IMPLANT DENTAL, and by hand search in relevant journals and throughout the selected papers. Results: This revision was carried out based on 50 papers focused on several prosthodontics-related risk factors that were grouped as follows: implant-connection, loading protocol, transmucosal abutments, prosthetic fit, provisionalization, type of retention, impression technique, fabrication technique, and occlusion. More than a half of the studies were systematic reviews (30%), meta-analysis (16%) or prospective evaluations of prosthesis with various kinds of events (18%). But also narrative reviews of literature (14%) and in vitro/animal studies (16%) were found. Conclusions: The current literature provides insufficient evidence for most of the investigated topics. However, based on the accumulated data, it seems reasonable to defend that the best treatment approach is the use of morse taper implants with transmucosal abutments, recorded by means of rigidly splinted copings through the pick-up technique, and screwed by milled prosthesis occlusally adjusted to minimize functional overloading.

The Coronavirus disease due to SARS-CoV-2 emerged in Wuhan city, China in December 2019 and rapidly spread more than 200 countries as a global health pandemic. There are more 3 million confirmed cases and around 207,000 fatalities. The primary manifestation is respiratory and cardiac but neurological manifestations are being reported in the literature as case reports and case series. The most common reported symptoms to include headache and dizziness followed by encephalopathy and delirium. Among the complications noted are Cerebrovascular accident, Guillian barre syndrome, acute transverse myelitis, and acute encephalitis. The most common peripheral manifestation was hyposmia. It is further noted that sometimes the neurological manifestations can precede the typical features like fever and cough and later on typical manifestations develop in these patients. Hence a high index of suspicion is required for timely diagnosis and isolation of cases to prevent the spread in neurology wards. We present a narrative review of the neurological manifestations and complications of COVID-19. Our aim is to update the neurologists and physicians working with suspected cases of COVID-19 about the possible neurological presentations and the probable neurological complications resulting from this novel virus infection.

It is currently recognized that an injudicious strategy in the last decades has been not only focusing of research typically on caries in children, but also the narrow focusing on fluoride, because despite sufficient availability of fluoride in water and oral healthcare products, caries levels escalate steadily as people get older and caries remain a main public health issue to be settled. In the last two decades the scientific community intensified efforts of exploring other products for caries prevention, herbal products being one of these approaches. Because preliminary evidence indicated that clinical trials for caries prevention with herbal products are heterogeneous in design, quality and products evaluated, we performed a scoping review intended to explore the main characteristics of such clinical trials. From an initial collection of 1986 unique papers from different literature databases, 56 articles satisfied the inclusion and exclusion criteria. The species investigated, dosage forms, study designs, duration of intervention, controls, endpoints, quality of reporting and risk of bias are discussed. 85.71% of the trials reviewed here reported positive results but given the methodological flaws and biases affecting them, it is difficult to conclude on the efficacy of those products based on the studies published thus far.

Background and Objectives: Clinical trials are a critical step in the development of new medicines and medical devices, testing the efficacy and safety of new treatment regimens. However, if the results of clinical trials are not made public, the evidence base on interventions is incomplete and possibly distorted, which lead to suboptimal treatment choices and negatively affect public health. This study analyses and contrasts the laws and regulations governing clinical trial registration and reporting in China and the United States. Methods: We used desk research to compile, assess and compare current laws, regulations, compliance patterns, and enforcement mechanisms and actions in China and the United States (U.S.). Policy documents were downloaded from Chinese and U.S. government websites. A spreadsheet analysis was utilized for direct comparison. Results: Both China and the U.S. have laws and regulations governing clinical trial registration and reporting. Chinese legislation covers a broader range of trials. In the U.S. trial results must be disclosed to both the national regulator and the public, while Chinese law mandates disclosure to the regulator alone. Cross-country comparisons of regulatory compliance by trial sponsors are impossible due to the opacity of the Chinese data platform. Neither country effectively ensures that all clinical trial results are made public as required by the Declaration of Helsinki and recommended by the WHO. Interpretation: While neither country is perfect, both may be able to learn from each other. There is a major gap in the literature regarding the extent of non-publication of clinical trial results by sponsors operating in China.

About half of the world's population is at risk of dengue infection. Epidemics of dengue fever caused an increased risk of morbidity and mortality in recent years, which led to the exploration of vaccines as a preventive measure. This systematic review and meta-analysis aimed to evaluate the efficacy, immune response, and safety of dengue vaccines in children by analyzing clinical trials. The review followed standard procedures for data extraction using PRISMA guidelines, and searching multiple databases including PubMed, CINAHL, Medline, Health Source, Science Direct, and Academic Search Premiere. Eligible studies involved children (0-17 years). Cochrane Collaboration criteria were used for quality assessment, with thematic data synthesis and meta-analysis. Among 38 selected studies, dengue vaccines showed varying efficacy against all four serotypes. CYD-TDV (Dengvaxia®), and Tekade (TAK-003) vaccines demonstrated strong protection against severe dengue, but their long-term efficacy varied. Vaccines triggered satisfactory immune responses, notably in those previously exposed to dengue. Safety profiles were mostly favorable, noting mild adverse events post-vaccination. Meta-analysis supported vaccine efficacy and immune response, but safety concerns warrant further exploration. In conclusion, dengue vaccines demonstrated promising efficacy and immune response, particularly against severe manifestations.

Orthohantaviruses can cause two types of human infections: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is a zoonotic disease transmitted by multiple rodent species. Yunnan Province in southwest China is the natural foci of HFRS, and Dali Prefecture in Yunnan Province has the highest incidence of HFRS; however, the precise status of orthohantavirus infection in Dali Prefecture remains unknown. To this end, we obtained clinical data of HFRS patients from the medical records of the People's Hospital of Xiangyun County in Dali Prefecture from July 2019 to August 2021. We collected epidemiological data of HFRS patients through interviews and investigated host animals using the night clip or night cage method. We systematically performed epidemiological analyses of patients and host animals. The differences in the presence of rodent activity at home (2=8.75, P=0.031&lt;0.05), of rodent-proof equipment in the food (2=9.19, P=0.025&lt;0.05), and of rodents or rodent excrement in the workplace (2=10.35, P=0.014&lt;0.05) were statistically different in the four clinical types, including mild, medium, severe, and critical HFRS-associated diseases. Furthermore, we conducted molecular detection of orthohantavirus in host animals. The total orthohantavirus infection rate of rodents was 2.7% (9/331); the specific infection rate of specific animal species was 6.1% (5/82) for the Apodemus chevrieri, 100% (1/1) for the Rattus nitidus, 3.8% (2/53) for the Rattus norvegicus, and 12.5% (1/8) for the Crocidura dracula. In this study, a total of 21 strains of orthohantavirus were detected in patients and rodents. The 12 orthohantavirus strains from patients showed a closer relationship with Seoul orthohantavirus (SEOOV) L0199, DLR2, and GZRn60 strains; the six orthohantavirus strains from Rattus norvegicus and Apodemus chevrieri were closely related to SEOOV GZRn60 strain; One strains (XYRn163) from Rattus norvegicus and one strain (XYR.nitidus97) from Rattus nitidus were closely related to SEOOV DLR2 strain; the orthohantavirus strain from Crocidura dracula was closely related to the Luxi orthohantavirus (LUXV) LX309 strain. In conclusion, patients with HFRS in Xuangyun County of Dali Prefecture are predominantly affected by SEOOV, with multiple genotypes of orthohantavirus in host animals, and most importantly, these orthohantavirus strains constantly demonstrated zoonotic risk in humans.

Background In this study, we describe our clinical experience with the fifth-generation of a breast implant with a smooth, fine surface from a Korean manufacturer (BellaGel^Ò SmoothFine; HansBiomed Co. Ltd., Seoul, Korea) in Asian women. Methods We analyzed 223 women (mean age=35.28±9.45 years and mean follow-up period=12.03±2.48 months), comprising 118 bilateral cases and 109 unilateral ones, who received breast augmentation using the BellaGel^Ò SmoothFine at our hospital between June 4, 2018 and February 28, 2019. For safety assessment, we analyzed frequencies of postoperative complications and overall survival of the BellaGel^Ò SmoothFine. Results Postoperatively, complications (12 cases, 5.38%) include asymmetry (3 cases, 1.35%), hematoma (2 cases, 0.90%), hypertrophic scars (2 cases, 0.90%), wound disruption (2 cases, 0.90%), rippling (1 case, 0.45%), capsular contracture (1 case, 0.45%), stretch deformities with skin excess (1 case, 0.45%). In addition, time-to-events were calculated as 10.94±0.64 months (95% CI 9.69-12.19) and the survival rate reached 0.290±0.168 (95% CI 0.094-0.901) at 12 months postoperatively. Conclusions Here, we describe our clinical experience with the BellaGel^Ò SmoothFine. Our results are of significance in that this is the first report about the fifth-generation of a breast implant with a smooth, fine surface from a Korean manufacturer in Asian women.

AK is a common precancerous skin condition that requires effective detection and treatment monitoring. To improve the monitoring of AK burden in clinical settings with enhanced automation and precision, the present study evaluates the application of semantic segmentation based on the U-Net architecture (AKU-Net). AKU-Net employs transfer learning to compensate for the relatively small dataset of annotated images and integrates a recurrent process based on convLSTM to exploit contextual information and address the challenges related to low contrast and ambiguous boundaries of AK-affected skin regions. We used an annotated dataset of 569 clinical photographs from 115 patients with actinic keratosis to train and evaluate the model. From each photograph, patches of 512x512 pixels were extracted using translation lesion boxes that encompass lesions in different positions and capture different contexts of perilesional skin. In total, 16488 translation augmented crops were used for training the model, and 403 lesion center crops were used for testing. To demonstrate the improvements in AK detection, AKU-net was compared with plain U-Net and U-Net++ architectures. The experimental results highlighted the effectiveness of AKU-Net, improving both automation and precision over existing approaches, paving the way for more effective and reliable evaluation of actinic keratosis in clinical settings.

New digital interventions have shown potential in managing asthma and improving patients' quality of life compared with conventional interventions. Our objective was to conduct an exhaustive survey of the application of digital health technologies in evaluating, treating, and self-managing psychological and psychopathological elements linked to asthma. We analyzed a compendium of research papers and systematic reviews pertaining to asthma, encompassing themes such as outdoor air pollution, early life wheezing disorders, atopic dermatitis, digital strategies for asthma self-management, psychiatric conditions and asthma, familial impacts on pediatric asthma, and the utilization of mobile health apps for managing asthma. We scrutinized eight chosen studies to evaluate the capacity of digital health technologies to enhance the man-agement and treatment outcomes of psychological factors related to asthma. The studies under review indicate that eHealth interventions, mixed reality instruments, mHealth technolo-gy-augmented nurse-led interventions, and smartphone apps incorporating Bluetooth-enabled sensors for asthma inhalers can markedly enhance self-management of symptoms, quality of life, and mental health outcomes, particularly in children and adolescents with asthma. Nonetheless, additional research is required to ascertain their efficacy and practicability across diverse populations and environments. Customized interventions that cater to the unique needs and preferences of asthma patients and associated psychological elements are vital to ensure the persistent and equitable adoption of these technologies. We underscore the significance of addressing psychological elements in the management and treatment of asthma and advocate for ongoing research and development in this domain.

Despite great strides being achieved in improving cancer patients’ outcomes through better therapies and combinatorial treatment, several hurdles still remain due to therapy resistance, cancer recurrence and metastasis. Drug resistance, culminating in relapse and metastatic disease continue to be associated with fatal disease. Cancer stem cells (CSCs) are a subpopulation of cancer cells known to be resistant to therapy and cause metastasis. Whilst the debate on whether CSCs are the origins of the primary tumor rages on, CSCs have been further characterised in many cancers with data illustrating that CSCs display great abilities to self-renew, withstand therapies due to enhanced epithelial to mesenchymal (EMT) properties, enhanced expression of ABC membrane transporters, activation of several survival signaling pathways and increased immune evasion DNA repair mechanisms. CSCs also display great heterogeneity with the consequential lack of specific CSC markers presenting a great challenge to their targeting. In this updated review we re-visit CSCs within the tumor microenvironment (TME) and present novel treatment strategies targeting CSCs. These promising strategies include targeting CSCs-specific properties using small molecule inhibitors, immunotherapy, microRNA mediated inhibitors, epigenetic methods as well as targeting CSC niche-microenvironmental factors and differentiation. Lastly, we present recent clinical trials undertaken to try to turn the tide against cancer by targeting CSC-associated drug resistance and metastasis.

Because the including of human anatomy forms the foundation for clinical medicine, it has contributed a pivotal role in medical education for many centuries. Thus with advancements in the science of modern, current day medicine, its continued place in the medical school curriculum deserves careful attention. In an attempt to provide guidance to decision-makers involved in clinical anatomy curriculum development at the medical school level, the Educational Affairs Committee of the American Association of Clinical Anatomists (AACA) developed this document, which defines the contours of a gross anatomy curriculum leading to the M.D. or D.O. degree. The main body of the document sets forth the anatomical concepts as well as the subject matter a student should master prior to graduation from medical school. Gross anatomy dissection is still a crucial topic in graduate and medical school. The nature and content of gross anatomy, which was historically regarded as a core course in the first year of medical education in MBBS, MD, DO, and some PhD and Graduate curricula as well as in other disciplines of selective graduate education and non-allopathic medical programs, have been significantly impacted by emerging challenges in the pedagogy of delivering medical education in the past ten years. A seemingly ever-increasing emphasis on additional modules in molecular biology, emerging pharmacotherapeutics and pathophysiology content have resulted in a condensation and apparent erosion of previously allotted classroom and laboratory hours in the gross anatomy curriculum. In addition, an imposition of financial constraints and a decreasing availability of sufficient cadaver donations to support gross anatomy dissection labs has also occurred in some locations. An innovative clinically focused cadaveric anatomy program is described which has improved the delivery and content retention of medical and graduate students and has become one of the most sought-after modules in the revised clinically oriented curriculum and has been deemed highly relevant to current medical education and graduate studies.

Computed tomography (CT) is a widely employed imaging modality with diverse clinical applications in pediatric and adult populations, offering numerous advantages. Despite several alternatives to imaging modalities with ionising radiation, CT scans have demonstrated persistent global popularity, contributing to a substantial amount of effective radiation doses for patients. This exposure results in hazards, including stochastic effects that amplify the radiation-induced cancer risk proportionally to the radiation dose received. CT-related radiation comprises a substantial portion of cumulative effective doses within diagnostic radiology, specifically impacting younger patient cohorts undergoing repeated investigations for chronic diseases over time. Scientific literature over recent decades has explored various methods to mitigate radiation doses during medical imaging. One notable strategy involves implementing low-dose and ultralow-dose CT protocols, maintaining diagnostic efficacy in acute and non-acute medical and surgical conditions. Utilising innovative image reconstruction algorithms, such as iterative reconstruction and emerging deep-learning algorithms based on artificial intelligence, plays a pivotal role in achieving an approximately 80% reduction in patient radiation compared to standard doses. This review article discusses the significance of low-dose protocols across a spectrum of acute and chronic medical conditions affecting different body systems.

Coronavirus disease 2019 (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached a global epidemic across the world after first reported in Wuhan, China’s Hubei province in December 2019. The pandemic is also associated with acute respiratory distress syndrome (ARDS) characterized by excess inflammation, progressive arterial hypoxemia and dyspnea. Mesenchymal stem/ stromal cells (MSCs) have been investigated as treatment for ARDS due to immunomodulatory property. Exosomes derived from MSCs play an important role in paracrine signaling of MSCs, thereby contributed to immunomodulation of the immune microenvironment. Exosomes are emerged as potential alternative to MSC cell therapy with superiority of safety. In this review, we will introduce MSC-derived exosomes and briefly discuss current progress on MSCs and exosomes in ARDS, which may have clinical implications in pathogenesis and treatment of COVID-19.

Aim. The analysis of incidence, clinical and morphological manifestations, and the prognosis of IgA nephropathy in the Northeastern Europe (NEE). Materials and methods. We enrolled cases with primary IgA nephropathy (IgAN) from 2005 to 2020 in the single-center retrospective study. Demographic and clinical parameters, histology data, and the treatment were analyzed. The outcomes were the occurrence of complete (PR) or partial remission (CR), renal replacement therapy (RRT), eGFR<15 ml/min/1.73m² and eGFR decrease ≥ 50%. The composite endpoint included all renal outcomes and was used to evaluate the risk of IgAN progression and associated factors. Results. The incidence of IgAN cases was 23.6% of all indication biopsies and 41.2% of primary immune glomerulopathies. At the time of the kidney biopsy, the proteinuria was 2.5 (1.5-5.0) g/24h, eGFR - 69 ± 32 ml/min/1.73 m². Proportions of cases with arterial hypertension and eGFR <60 ml / min / 1.73 m² were 75% and 36%, respectively. The prevalence of histological changes in accordance with the Oxford (MEST-C) classification was M1 - 40.5%, E1 -22.9%, S1-70.2%, T1-22%, T2 - 9%, C1-16.7%, C2 - 4.4%. In the follow-up of 27 (11; 61) months, 6 deaths occured (1.7%). The 10-year cumulative dialysis-free survival was 80% and progression-free survival was 56%. Remissions registered in 50% of cases, being more frequent in patients who received immunosuppression vs renoprotection (60% vs. 40%, p = 0.001). In multivariable Cox regression, the independent factors associated with the increased probability of IgAN progression were male gender, a younger age, higher blood pressure and hematuria, lower eGFR, interstitial fibrosis/ tubular atrophy (≥50%), the presence of peritubular capillaritis and any crescents. Compared to the cohorts of other ethnic or geographical origin, IgAN in the studied cohort were found to have more severe clinical and morphological presentations and faster progression rate. Conclusion. Being the most common glomerulopathy in the NEE population, IgAN has more pronounced clinical and morphological presentations. Considering the distinctive features of the disease, further research is warranted in order to establish approaches for enhancing risk stratification and treatment efficacy.

In a wide range of lymphoid neoplasms, the process of malignant transformation is associated to somatic mutations in B cells that affect the epigenetic machinery. Consequential alterations in histone modifications contribute to disease-specific changes in the transcriptional program. Affected genes commonly play important roles in cell cycle regulation, apoptosis-inducing signal transduction and DNA damage response, thus facilitating the emergence of malignant traits that impair immune surveillance and favor the emergence of different B-cell lymphoma subtypes. In the last two decades, the field has made a major effort to develop therapies that target these epigenetic alterations. In this review, we discuss which epigenetic alterations occur in non-Hodgkin B-cell lymphoma. Furthermore, we aim to present in close to comprehensive manner the current state-of-the-art in the preclinical and clinical development of epigenetic drugs. We focus on therapeutic strategies interfering with histone methylation and acetylation as these are most advanced in being deployed from the bench-to-bedside and have greatest potential to improve the prognosis of lymphoma patients.

People are increasingly encouraged to reduce animal food consumption and shift towards plant-based diets, however the implications for children’s health are unclear. In this narrative review of research in high-income settings, we summarize evidence on the increasing consump-tion of plant-based diets in children, and update an earlier systematic review regarding their associations with children’s health outcomes. The evidence indicates that vegan but not vege-tarian diets can restrict growth relative to omnivorous children, and increase the risk of being stunted and underweight although the percentage affected is relatively small. Bone mineral content is reduced in vegetarian and especially vegan children, compared to omnivores. Both vegetarian and vegan children who do not use vitamin B12 supplements manifest with B12 defi-ciency, however supplementation rectifies this problem. Both vegetarians and vegans have lower concentrations of 25 (OH)D if unsupplemented, and lower body iron stores, but usually have normal iron metabolism markers. Both groups are at risk of iodine deficiency and this might affect thyroid health. Children consuming a vegan diet have more favorable lipid profile than omniv-orous children, however the results for vegetarian diet are inconsistent and vary by outcome. Based on the same scientific evidence, national and international dietary recommendations are heterogeneous, with some countries supporting plant-based diets among infants, children and adolescents, and others discouraging them. We offer a research roadmap, highlighting what is needed to provide adequate evidence to harmonize dietary recommendations for plant-based diets in children. A number of measures should urgently be introduced at international and na-tional levels to improve the safety of their use in children.

Objective: The objective of this study is to determine the epidemic dynamics and clinical features of COVID-19 in southern Hainan Island, China, and provide experience for other tropical areas of the world. Methods: This retrospective study included confirmed cases of COVID-19 in southern Hainan. All enrolled patients were treated in Sanya, and data on epidemiological and clinical features of the disease and infection prevention and control measures adopted by the local government during the epidemic were collected. Results: Of the 74 cases, 71 (95.95%) were imported from Wuhan, Hubei Province (47, 63.51%), other cities in Hubei Province (11, 14.86%), or provinces other than Hubei and Hainan (13, 17.57%). Three (4.06%) patients were infected in southern Hainan, including one autochthonous case in Sanya. Fifty-four cases (72.97%) were detected in Sanya, and 27 cases (27.03%) were diagnosed in other cities. The rate of severe or critical cases was 28.38% (21/74), and mortality was 2.7% (2/74). The serum lactate levels and base excess of severe-critical patients were higher than those of patients with mild-moderate disease. Multivariate logistic regression analysis showed that chronic conditions were risk factors for severe and critical COVID-19. Seventy-four patients were diagnosed with COVID-19 over a 22-day period in Sanya, and the epidemic period in the city was 48 days. The outbreak was controlled rapidly because the local government adopted strict infection prevention and control measures. Conclusions: The clinical characteristics of COVID-19 in Hainan Island were similar to those reported in other regions. In Sanya, the rate of severe and very severe cases was higher than in other regions; however, most cases were imported, and there was only one autochthonous case. The rapid control of the outbreak in Sanya may be related to the tropical climate, adoption of strict infection prevention and control measures, daily reporting of new cases, increased public awareness about the epidemic, and other emergency actions implemented by the local government.

To gain insight into the real-life care of patients in the healthcare system, data from hospital information systems and insurance systems are required. Consequently, linking clinical data with claims data is necessary. To ensure their syntactic and semantic interoperability, the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) was chosen. However, there is no detailed guide that would allow researchers to follow a consistent process for data harmonization. Thus, the aim of this paper is to conceptualize a generic data harmonization process for OMOP CDM. For this purpose, we conducted a literature review focusing on publications that address the harmonization of clinical or claims data in OMOP CDM. Subsequently, the process steps used and their chronological order were extracted for each included publication. The results were then compared to derive a generic sequence of the process steps. From 23 publications included, a generic data harmonization process for OMOP CDM was conceptualized, consisting of nine process steps: dataset specification, data profiling, vocabulary identification, coverage analysis of vocabularies, semantic mapping, structural mapping, extract-transform-load-process, qualitative and quantitative data quality analysis. This process can be used as a step-by-step guide to assist other researchers in harmonizing source data in OMOP CDM.

The aim of the study was to analyze the oral etiology of patients with odontogenic sinusitis (ODS）and to compare the differences in demographic data, clinical symptoms, extent of sinus involvement, bone penetration of the maxillary sinus floor (MSF) between different etiologies. A retrospective investigation was conducted on 103 patients with ODS recruited from Beijing Tongren Hospital. All enrolled patients underwent sinus CT, nasal endoscopy, and oral examination. A comparison of the patients' clinical symptoms, extent of involvement of the sinuses, and bone resorption of the MSF according to odontogenic etiologies was conducted. Follow-up was based on symptoms, clinical examination. The most common odontogenic etiologies were endo-periodontal lesions (EPL. 49.5%), apical periodontitis (AP, 32.0%) and periodontitis (PE, 8.7%). There were statistically significant differences in age (P=0.002), sex (P=0.036), inflammation involving the ethmoid sinus (P=0.037), and bone penetration of the MSF (P<0.001) between the AP, EPL, and PE groups. There were no significant differences in sinusitis symptoms (P>0.005) among patients with different odontogenic etiologies. In conclusion, EPL is a neglected oral etiology with a destructive effect on the bone of the MSF, and Should receive more attention in diagnosis and treatment.

Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2), later renamed Coronavirus Disease 2019 (COVID-19) was first identified in Wuhan, China, in early December 2019. Initially, the China office of the World Health Organization was informed of numerous cases of pneumonia of unidentified etiology in Wuhan, Hubei Province on December 31, 2019. This would subsequently result in a global pandemic with over 76 million confirmed cases of COVID-19 and 6.9 million deaths reported to the WHO. We have analyzed most of the data published since the beginning of the pandemic to compile this comprehensive review of SARS-CoV-2. We look at the core ideas, such as the etiology, epidemiology, pathogenesis, clinical symptoms, diagnostics, histopathologic findings, consequences, therapies, and vaccines. We have also included the long-term effects and myths associated with some therapeutics of COVID-19. This study comprehensively assesses of the SARS-CoV-2 virology, vaccines, medicines, and significant variants identified during the pandemic. Our review article is intended to provide medical practitioners with a better understanding of the fundamental sciences, clinical treatment, and prevention of COVID-19. As of June 2023, this paper contains the most recent data made accessible.

The 2019 COVID-19 pandemic caused by SARS-CoV-2 has resulted in many fatalities worldwide. Despite various types of supportive care, mortality rates for patients with comorbidities remain high. To explore alternative treatment options, interferons (IFNs) have emerged as promising therapeutic drugs for SARS-CoV-2. This review aims to investigate the potential of IFNs as a drug with details on their mechanisms of action, and available data on their use with ongoing clinical trials, results, potential limitations, and challenges. Recently published research articles, which were systematically searched through online databases, have been selected and found that IFNs have colossal potential in treating SARS-CoV-2 infection by modulating the host's immune response and inhibiting viral replication and decreasing the severity of disease and hospitalization (p = 0.03, ±0.05) and (p = 0.04, ±0.05) respectively. However, due to less available data, more controlled and randomized trials are needed to confirm the efficacy and safety of IFN therapy. The optimal dosing and duration of IFN therapy also remain to be determined. Although further research is needed the wait for ongoing clinical trial results under investigation is also important for a better understanding of IFN therapy.

Our search of existing cancer databases aimed to assess the current landscape and identify key needs. We analyzed 71 databases, focusing on genomics, proteomics, lipidomics, and glycomics. We found a lack of cancer-related lipidomic and glycomic databases, indicating a need for further development in these areas. Proteomic databases dedicated to cancer research were also limited. To assess overall progress, we included human non-cancer databases in proteomics, lip-idomics, and glycomics for comparison. This provided insights into advancements in these fields over the past eight years. We also analyzed other types of cancer databases, such as clinical trial databases and web servers. Evaluating user-friendliness, we used the FAIRness principle to assess findability, accessibility, interoperability, and reusability. This ensured databases were easily accessible and usable. Our search summary highlights significant growth in cancer databases while identifying gaps and needs. These insights are valuable for researchers, clinicians, and database developers, guiding efforts to enhance accessibility, integration, and usability. Addressing these needs will support advancements in cancer research and benefit the wider cancer community.

Cryoglobulinaemia is characterised by immunoglobulins which precipitate at temperatures be-low 37°C and redissolve on warming. Monoclonal IgM immunoglobulin may be associated with type I and II cryoglobulinaemia with underlying Waldenström macroglobulinemia, monoclonal gammopathy of undetermined significance or other non-Hodgkin lymphoma. We review the clinical characteristics, laboratory testing and suggest a management approach for monoclonal IgM associated cryoglobulinaemia. Laboratory testing is critical as even a minimal amount of measurable cryoglobulin may result in symptoms. Accurate detection of cryoglobulins may be challenging and care must be taken with preanalytical variables and repeat testing of monoclo-nal protein and cryoglobulins is indicated if clinical suspicion is high. Presentations range from asymptomatic disease to multisystem involvement so careful evaluation of the features and thorough interrogation of organ systems and the underlying clone is critical. Immediate man-agement is required for clinical red flag features. Due to their rarity, data to inform treatment decisions are scant and collaborative research is imperative to aid defining optimal treatment strategies.

Background: Primary cardiac sarcomas (PCS) are extremely rare malignant tumors involving the heart. Only isolated case reports have been described. There is a paucity of data on the epidemiological characteristics of PCS. This study has the objective of investigating the epidemiologic characteristics, survival outcomes, and independent prognostic factors of PCS. Methods: We enrolled a total of 362 patients with PCS, between 2000 and 2017, by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of PCS. Variables with a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. Results: Crude analysis revealed a high OM in age 80+ (HR=5.958, 95% CI 3.357-10.575, p=0), followed by age 60-79 (HR=1.429, 95% CI 1.028-1.986, p=0.033); and PCS with distant metastases (HR=1.888, 95% CI 1.389-2.566, p=0). Patients that underwent surgical resection of the primary tumor and patients with malignant fibrous histiocytomas (HR=0.657, 95% CI 0.455-0.95, p=0.025) had a better OM (HR=0.606, 95% CI 0.465-0.791, p=0). The highest cancer-specific mortality was observed in age 80+ (HR=5.037, 95% CI 2.606-9.736, p=0) and patients with distant metastases (HR=1.953, 95% CI 1.396-2.733, p=0). Patients with malignant fibrous histiocytomas (HR=0.572, 95% CI 0.378-0.865, p=0.008) and those who underwent surgery (HR=0.581, 95% CI 0.436-0.774, p=0) had a lower CSM. Multivariate Cox proportional hazard regression analyses revealed higher OM in the age group 80+ (HR=13.261, 95% CI 5.839-30.119, p=0) and advanced disease with distant metastases (HR=2.013, 95% CI 1.355-2.99, p=0.001). Lower OM was found in patients with rhabdomyosarcoma (HR=0.364, 95% CI 0.154-0.86, p=0.021) and widowed patients (HR=0.506, 95% CI 0.263-0.977, p=0.042). Multivariate Cox proportional hazard regression analyses of CSM also revealed higher mortality in the same groups, and lower mortality in patients with Rhabdomyosarcoma. Conclusion: In this United States population-based retrospective cohort study using the SEER database, we found that cardiac rhabdomyosarcoma was associated with the lowest CSM and OM. Furthermore, as expected, age and advanced disease at diagnosis were independent factors predicting poor prognosis. Surgical resection of the primary tumor showed lower CSM and OM in the crude analysis but when adjusted for covariates in the multivariate analysis, it did not significantly impact the overall mortality or the cancer-specific mortality. These findings allow for treating clinicians to recognize patients that should be referred to palliative/hospice care at the time of diagnosis and avoid any surgical interventions as they did not show any differences in mortality. Surgical resection in patients with poor prognoses should be reserved as a palliative measure rather than an attempt to cure the disease.

Many clinical trials end uninformatively. Informativeness, in the context of clinical trials, defines whether a study’s results definitively answer its research questions with meaningful next steps. One subset of these trials are those focused on global health set in low-resource settings. Global health clinical trials benefitting people in low-resource settings are funded primarily by a limited number of large foundations, pharmaceutical firms (“industry”), and national governments. While clinical trial protocols are required to go through reviews in regulatory and ethical domains, outside of industry-funded trials, funders rarely require focused scientific design reviews. There are no documented standards and processes, or even best practices, for funders to perform scientific reviews after the funding commitment. Considering the investment in and standardization of ethical and regulatory reviews, and the prevalence of studies ending without clarity or never finishing, it may be that scientific reviews of trial designs with a focus on informativeness offer the best chance for improved outcomes and return on investments in clinical trials. A maturity model is a helpful tool for knowledge transfer to help grow capabilities in a new area, or for those looking to perform a self-assessment in an existing area. Such a model is offered for scientific design reviews of clinical trial protocols: a valuable and often-neglected governance step for funders or sponsors, among others. This maturity model includes 11 process areas and 5 maturity levels. Each of the 55 process area levels is populated with descriptions on a continuum toward an optimal state to improve trial protocols in the area of risk of failure. This tool allows for prescriptive guidance on next investments to improve attributes of post-funding reviews of trials, with a focus on informativeness.