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Article
Medicine and Pharmacology
Dentistry and Oral Surgery

Claudio Stacchi,

Antonio Rapani,

Marco Montanari,

Rebecca Martini,

Teresa Lombardi

Abstract: Background: Plasma surface activation of dental implants has been proposed to enhance osseointegration by improving titanium surface chemistry. However, clinical data in humans remain limited. This randomized controlled trial aimed to assess the effect of vacuum plasma treatment on early implant stability in partially edentulous patients. Materials and Methods: In this single-blind, split-mouth randomized controlled trial, 24 patients requiring two contralateral implants were enrolled. Each patient received one plasma-treated implant and one untreated control implant. Vacuum plasma activation was performed immediately before insertion using a specific system (Plasma X Motion, MegaGen, Gyeongbuk, South Korea). Implant stability was assessed at placement and at 7, 14, 21, 28, 42, 60, and 90 days using resonance frequency analysis (Implant Stability Quotient, ISQ). Results: All 48 implants achieved successful osseointegration at 90 days, with no adverse events or complications. Mean insertion torque did not differ significantly between groups (p = 0.86). Both groups exhibited a typical initial reduction in stability, with the lowest ISQ values at 21 days. Plasma-treated implants showed a more favorable recovery pattern, with significantly higher ISQ values than controls at 60 and 90 days (p = 0.04 and p = 0.03, respectively). Nevertheless, the absolute difference in ISQ values between groups remained limited. Conclusion: Vacuum plasma activation of titanium implants may contribute to a more favorable early stability pattern, although both plasma-treated and untreated implants demonstrated predictable osseointegration outcomes. Further research with larger cohorts and longer follow-up is needed to fully assess the clinical significance of these findings.
Review
Medicine and Pharmacology
Internal Medicine

Antoni F. Araszkiewicz,

Krzysztof Jańczak,

Paweł Wójcik,

Bartłomiej Białecki,

Szymon Kubiak,

Michał Szczechowski,

Danuta Januszkiewicz-Lewandowska

Abstract: The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a process essential for the methylation of homocysteine to methionine. Polymorphisms in the MTHFR gene can reduce enzyme activity, disrupting the folate cycle and leading to hyperhomocysteinemia. The two most common polymorphisms associated with this gene are 667C>T (rs1801133) and 1298A>C (rs1801131). Background: This review provides a comprehensive summary of current knowledge regarding MTHFR polymorphisms, with a particular focus on their potential impact on disease susceptibility. We hope this review will serve as a valuable resource for understanding the significance of MTHFR polymorphisms and their complex relationships with various diseases. Methods: For this review, we prioritized recent evidence, focusing on reviews and meta-analyses published between 2015 and 2025, sourced from PubMed and Google Scholar. Results: We explore the connection between these polymorphisms and a broad spectrum of medical conditions, including: cardiovascular diseases and oxidative stress pathology, neurological and psychiatric disorders, such as Autism Spectrum Disorder, Alzheimer’s disease, Schizophrenia, and Major Depressive Disorder, fertility, pregnancy, and neonatal complications, including recurrent pregnancy loss, preeclampsia, preterm birth, low birth weight, and neural tube defects, metabolic disorders, such as diabetes mellitus, inflammatory bowel disease, and non-alcoholic fatty liver disease, oncological conditions, including breast, prostate, and ovarian cancers, as well as leukemia, autoimmune diseases, particularly rheumatoid arthritis. Conclusions: While some diseases have a well-established association with MTHFR polymorphisms, others require further investigation. Our analysis highlights the crucial role of environmental factors, such as ethnic background and dietary folate intake, in influencing study outcomes.
Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Glenda Aparecida Peres dos Santos,

Hanna da Silva Bessa da Costa,

Carmem Moulin Magalhaes,

Carolina gianella cobo chantong,

Roberto Mogami,

Agnaldo José Lopes

Abstract: In December 2019, the World Health Organization (WHO) reported an outbreak of pneumonia in Wuhan, China, caused by severe acute respiratory syndrome coronavirus 2. Computed tomography (CT) is the primary imaging modality used to diagnose and monitor severe acute respiratory syndrome caused by SARS-CoV-2. However, its routine use is expensive and produces large amounts of radiation. The aim of this study was to define chest radiography (CXR) patterns for COVID-19 and correlate them with clinical and outcome variables to achieve early and effective diagnosis using a cheaper and more accessible imaging method compared to CT. We analyzed CXR images and RT-PCR results of patients with COVID-19, categorizing them into typical, possible, atypical, or negative patterns. The results showed that CXR is effective and economical in evaluating COVID-19, with type 3 opacities associated with more severe outcomes and type 1 opacities with early stages of infection. Moreover, patients with comorbidities, age over 60 years, and the need for mechanical ventilation had worse outcomes. In conclusion, CXR can be an effective and inexpensive tool in the evaluation of COVID-19, especially in high-demand scenarios. Standardization of radiographic findings is also important for the improvement of diagnostic accuracy and clinical management of COVID-19.
Review
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Ahmad Reza Rezaei,

Tarun Mishra

Abstract: Fungal infections occurring across the kingdom boundaries, a novel phenomenon to humans, will be discussed herein through the lens of plant pathogens that are now recognized as infecting humans. We highlight major pathogens among them, such as Fusarium species, Exserohilum rostratum, Sporothrix schenckii, and the more recently identified pathogen, Chondrostereum purpureum, which exemplify a wide spectrum of clinical manifestations ranging from superficial keratitis and lymphocutaneous infections to central nervous system involvement and deep-seated abscesses. This review compiles epidemiological data, detailed case studies and outbreak reports, including the 2012 Exserohilum rostratum meningitis outbreak in the USA and a solitary case of C. purpureum infection in a plant mycologist from Kolkata, India. This Reviews critically appraises diagnostic strategies that amalgamate traditional culture methods, imaging modalities and cutting-edge molecular techniques (e.g., PCR, DNA sequencing and MALDI-TOF mass spectrometry) to mitigate the challenges associated with rapid and accurate determination of pathogens. Several therapeutic strategies are discussed in depth, with the emphasis that pharmacological and surgical interventions should be based on the specific pathogen and clinical setting. The review also highlights the other public health and agricultural consequences of these infections and the potential contribution of environmental factors like climate change and agricultural fungicide use to pathogen evolution. This synthesis advocates for a One Health approach by endeavours to unite clinical medicine, plant pathology, and environmental science within the production of evidence, so as to inform future strategies for the surveillance, diagnosis and management of these complex and evolving infectious threats.
Article
Medicine and Pharmacology
Oncology and Oncogenics

Carlos Perez-Stable,

Alicia de las Pozas,

Medhi Wangpaichitr,

Wei Sha,

Haibo Wang,

Renzhi Cai,

Andrew V. Schally

Abstract: Antagonists of GHRH have experimental therapeutic value but as single agents are not likely to improve clinical outcomes, especially in advanced prostate cancer resistant to androgen deprivation therapy. Our objective is to identify anti-cancer drugs that in combination with MIA-602 or -690 GHRH antagonists increase cell death in all types of prostate cancer. We identified inhibitors of PI3Ka or PI3Kb that consistently increased cell death when combined with MIA-602/690. The PI3K family is critical in mediating upstream signals from receptors to downstream AKT/mTOR signaling pathways and has an important role in cancer progression. Results revealed that MIA-602/690 alone decreased androgen receptor and likely enhanced PI3K (negative feedback), which is then countered by addition of PI3K inhibitors. Furthermore, MIA-602/690 + PI3K inhibitor combination affected multiple signaling pathways, including apoptosis (anti-apoptotic Mcl-1L switch to pro-apoptotic Mcl-1S), proliferation (E2F1, cyclin A), PI3Ka/b, AKT, and ERK. Similar results were obtained with a more clinically relevant acetate salt form of MIA-602/690. Identification of PI3K as a drug target for prostate cancer is significant because PTEN (negative regulator of PI3K) loss of function occurs in 40-50% and PIK3CA mutation/amplification occurs in 60% of prostate cancer patients, leading to a poor prognosis. The ability of the MIA-602/690 + PI3K inhibitor combination to alter multiple signaling pathways may weaken the activation of adaptive mechanisms resulting from each drug and improve efficacy.
Article
Medicine and Pharmacology
Pediatrics, Perinatology and Child Health

Javier Arredondo Montero,

Samuel Sáez Álvarez,

Andrea Herreras Martínez,

Ana Fernández-García,

Cristina Iglesias Blázquez

Abstract: Introduction: Inlet Patch (IP) is a congenital anomaly characterized by gastric heterotopia in the cervical esophagus. While extensively described in adults, it remains poorly characterized in pediatric populations.Material and Methods: This retrospective, single-center study included all pediatric patients (0–14 years) diagnosed with IP between 2018 and 2025. Sociodemographic and clinical data were collected. A blinded pathologist assessed the presence and severity of gastritis within the IP.Results: Nine patients (median age: 12 years) were included, 78% male. Cervical esophageal symptoms were identified in 67%, primarily dysphagia and gastroesophageal reflux disease-related complaints, although concomitant conditions such as eosinophilic esophagitis were frequently present. Endoscopic examination revealed characteristic well-demarcated salmon-red plaques in all patients, with multiple lesions observed in three cases. Histology confirmed gastric heterotopia with varying degrees of chronic inflammation in all cases. A strong correlation was observed between the severity of gastritis in the stomach, the severity of inflammation in the IP, and the presence of H. pylori, with 75% of patients with moderate-to-severe IP inflammation also exhibiting gastric H. pylori-associated gastritis. All patients except one received proton pump inhibitors, and symptoms improved in all cases.Conclusions: A thorough and targeted examination of the cervical esophagus significantly increased IP detection at our center, with most cases (88%) being diagnosed in the last 12 months. While mostly asymptomatic and incidental, IP can be symptomatic. In this case series, we found a correlation between the severity of inflammation in the IP, the severity of gastritis and the presence of H. pylori. Further studies are needed to define pediatric IP clinical significance and optimal management.
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Medicine and Pharmacology
Other

John J. Hines,

Joshua Roberts,

Douglas S. Katz

Abstract: Background and Clinical Significance: Hyperattenuating contents in the gastrointestinal (GI) tract detected on CT scans are commonly seen, and are almost always due to the purposeful ingestion of an oral contrast agent, usually barium or iodine based, used for evaluating the GI tract. Occasionally, other ingested material such as antacids or other medications, foreign objects, and medical devices, can also be hyperattenuating. While these are usually correctly identified, there is the potential for misdiagnosis of such material as a pathologic condition. Lokelma (sodium zirconium cyclosilicate (SZC)) is an agent which is being increasingly used to treat hyperkalemia, and which has a hyperattenuating appearance on CT due to the presence of zirconium, although this is not well not known to the radiologic community. We describe a case in which SZC was seen in the GI tract on CT, and misinterpreted as an acute GI bleed. Case Presentation: A 72-year-old woman underwent single (portal venous) phase intravenous contrast-enhanced abdominal and pelvic CT after presenting to the ED with a lower GI bleed. The CT showed intraluminal hyperattenuation within a loop of ileum which was diagnosed prospectively as an active GI bleed. A CT angiogram of the abdomen and pelvis performed the following day for follow-up showed the hyperattenuating contents to be present on the non-IV contrast enhanced series of the study, thereby proving that it was not due to active bleeding. Further investigation of the patient’s medical record showed that the patient was being treated with SZC for hyperkalemia. Conclusions: Sodium zirconium cyclosilicate (SZC) has a hyperattenuating appearance on CT. Knowledge of this appearance by radiologists and clinical staff can help avoid confusion and misdiagnosis.
Article
Medicine and Pharmacology
Hematology

Ewa Karakulska-Prystupiuk,

Magdalena Feliksbrot-Bratosiewicz,

Maria Król,

Agnieszka Tomaszewska,

Wiesław Wiktor Jędrzejczak,

Grzegorz Władysław Basak

Abstract: Background: Secondary immunodeficiencies in allo-HSCT (allogeneic hematopoietic stem cell transplantation) recipients increase the risk of viral reactivation, making vaccinations a vital issue. There is a paucity of data on the use of recombinant vaccine against herpes zoster (RZV) after allo-HSCT. Methods: The analysis included 149 recipients of allo-HSCT, transplanted in 2012-2022, mainly due to hematological malignancies (>95%). RZV was used from 2021 to 2023 according to the current recommendations of ACIP. The ELISA method was used to assess the VZV IgG antibody titers. Results: VZV reactivation was diagnosed in 49 out of 149(33%) patients before vaccination, including 5(3%) patients with reactivation within the first year after transplantation and the remaining 44(30%) within the subsequent three years. At that time majority of patients were not receiving acyclovir prophylaxis. The most common clinical manifestation of reactivation was involvement of intercostal nerves diagnosed in 40(81%) patients. Twenty-one recipients (median age: 41) received two doses of RZV (at median time-34 months after transplantation, range 12-84 months), the majority of them at an interval of 1 month. The serological post-vaccination response was confirmed in 12 recipients with a ratio of 2.38- 8.3 (median 5.095). The median number of total CD3+CD4+cells in vaccinated patients was 451/μl. Despite vaccination, four patients (19%, three with confirmed serological response) developed herpes zoster. Conclusions: Herpes zoster occurred mainly in the late period after allo-HSCT after completion of acyclovir prophylaxis in over 30% of recipients. The preliminary results indicate that RZV vaccination after allo-HSCT is safe but may have limited effectiveness.
Article
Medicine and Pharmacology
Surgery

Jessica Copeland,

Eliza Neal,

Tayyiaba Farooq,

Endel Orav

Abstract: Objectives: Overall survival (OS) of patients with stage 0 adenocarcinoma in situ (AIS) of the lung is not well characterized in the U.S. Specifically, there are a lack of data regarding the OS of patients with stage 0 AIS who do not receive treatment. We compared OS among stage 0 AIS patients who received surgery and those who received no treatment. Methods: OS of patients with stage 0 (TIS, N0, M0) AIS of the lung who received surgery versus no treatment from 2010-2018 in the National Cancer Data Base was evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis. Predictors of surgery were evaluated using multivariable logistic regression. Survival outcomes based on surgical approach were evaluated in a propensity score-matched subgroup analysis. Results: Of the 897 patients who were diagnosed with stage 0 AIS, 716 (79.8%) underwent surgical resection. A propensity score-matched analysis of 134 patients who received no treatment and 134 patients who underwent surgery showed that the surgical group had a significantly improved OS at five-years 85.8% (95% CI: 74.2-92.4%) compared to the group who received no treatment 62.8% (95% CI: 50.1-72.7%) (log-rank, p <0.0001). Subgroup propensity score-matched analysis showed no significant differences in OS at five-years in the surgical group who underwent a wedge resection 90.8% (95% CI: 83.8-94.8) compared to a lobectomy 94.9% (95% CI: 89.9-97.4%) (log-rank, p=0.19). Conclusions: In this national analysis, stage 0 AIS patients who underwent surgery had significantly better OS when compared to patients who did not receive treatment.
Review
Medicine and Pharmacology
Urology and Nephrology

Roberto Franco Villalba Bachur,

Gustavo Martin Villoldo

Abstract: Laparoscopic urological surgery has become a cornerstone in the treatment of various urological conditions, offering significant advantages over traditional open surgical approaches. These include smaller incisions, less tissue trauma, reduced intraoperative bleeding, less postoperative pain, shorter hospital stays, better cosmetic outcomes, and faster recovery times. Despite these benefits, laparoscopic surgery is not without risks, and major vascular injury (MVI) is one of the most severe and potentially life-threatening complications. This review explores the incidence, causes, and management strategies for MVI in laparoscopic urological surgery, highlighting the importance of early recognition, standardized protocols, and surgical expertise to optimize patient outcomes.
Article
Medicine and Pharmacology
Internal Medicine

Emre Hoca,

Nilsu Kalaycı,

Süleyman Ahbab,

İsmail Engin,

Hayriye Esra Ataoğlu

Abstract: Background/Objectives: Cardiovascular complications are the most common cause of mortality and morbidity in diabetic patients. Therefore, the aim of antidiabetic therapy should not only be to provide glucose regulation but also to protect patients from com-plications and related mortality. Brain natriuretic peptide (BNP) is a peptide secreted as a result of myocardial stress. BNP levels increase in conditions of increased myocar-dial stress, such as heart failure. It is important not only in diagnosis but also in fol-low-up. In our study, we aimed to evaluate BNP level and, thus, the factors affecting the risk of developing heart failure in the course of diabetes mellitus. Methods: This study was conducted at the University of Health Sciences, Haseki Training and Re-search Hospital diabetes outpatient clinic. Two hundred fifty-two patients met the in-clusion criteria and were enrolled in the study. Laboratory parameters, including BNP values, comorbidities, and anamnesis data, were recorded. Results: The mean BNP levels were significantly lower in patients using metformin and pioglitazone. Other antidiabetic medications were not associated with BNP levels. BNP levels were posi-tively correlated with age and diabetes duration and negatively correlated with hemo-globin. According to regression analysis, age, metformin use, and hemoglobin were found to independently affect BNP levels. Conclusions: Our findings suggest that metformin could potentially play a significant role in preventing the development of heart failure in diabetic patients without heart failure, owing to its favorable effects on myocardial stress. This suggests metformins potential in preventing heart failure in type 2 diabetic patients.
Article
Medicine and Pharmacology
Clinical Medicine

Qingbing Jiang,

Yifeng Shang,

Xiong Liao,

Wei Su

Abstract: Purpose: The optimal surgical strategy for the treatment of displaced intra-articular calcaneal fractures remains controversial.The purpose of this retrospective cohort study was to compare the clinical and radiologic outcomes of open reduction and plate fixation (ORPF) via the sinus tarsi approach versus percutaneous cannulated screw fixation (PCSF) in patients with displaced intra-articular calcaneal fractures with follow-up to 2 years.Methods: A retrospective analysis was performed on the records of all patients with displaced intra-articular calcaneal fractures (Sanders types II and III) who were admitted to two level I trauma centers between January 2018 and December 2022. Data were analyzed using propensity score matching (PSM) at a 1:1 ratio. The primary outcome was assessed using the AOFAS score for evaluating ankle function. Secondary outcomes included operative time, postoperative VAS, wound complication rates, and hardware removal rates. Radiological outcome assessment was conducted based on X-rays taken preoperatively and 3 months post-injury.Results: A total of 143 patients were included in the analysis. We successfully matched 62 patients in the ORPF cohort with 62 patients in the PCSF cohort using PSM. At 24 months, there was no significant difference in the AOFAS scores between the two groups (P > .05); similarly, there were no significant differences in radiological outcomes at 3 months postoperatively (P > .05). However, the PCSF group had significantly lower operative time (65 ± 35 min vs 95 ± 40 min, P < .01), postoperative VAS score (5 ± 1 vs 8 ± 1.5, P < .05), wound complication rates (3.2% vs 9.6% , P < .01), and hardware removal rates (14.5% vs 0, P < .01) compared to the ORPF group.Conclusion: In this study, we found that both surgical procedures resulted in satisfactory ankle function and radiological outcomes. The PCSF group was associated with lower VAS scores, fewer wound complications, a lower reoperation rate, and no cases requiring hardware removal.Keywords Intra-articular calcaneal fractures, Percutaneous fixation, Cannulated screws, Open reduction
Review
Medicine and Pharmacology
Oncology and Oncogenics

Wei Xu,

Qing Li,

Bin Liang

Abstract: Hepatocellular carcinoma (HCC) in intermediate and advanced stages remains a therapeutic challenge. Hepatic artery infusion chemotherapy (HAIC) is a well-established locoregional therapy for unresectable HCC. HAIC, either alone or in combination with systemic therapies, has shown encouraging therapeutic outcomes for the treatment of HCC patients with intermediate and advanced diseases in recent studies. This review summarizes the clinical advances in HAIC for HCC, highlighting HAIC regimens and their therapeutic outcomes.
Article
Medicine and Pharmacology
Clinical Medicine

Da-Long Chen,

Yu-Kai Lin,

Guei-Jane Wang,

Kuan-Cheng Chang

Abstract: Background: Out-of-hospital cardiac arrest (OHCA) survivors after extracorporeal cardiopulmonary resuscitation (ECPR) have a 50-70% mortality rate. However, the use of vasoactive inotropes during the first 24 h worsened the mortality rate. Be-cause of administering inodilators (e.g., levosimendan and milrinone) within 72 h of ECPR could facilitate extracorporeal membrane oxygenation (ECMO) weaning, it is crucial to determine whether the use of inodilators could im-prove mortality rates. Methods: This retrospective cohort study included 158 patients with OHCA of cardiac origin who had undergone ECPR and were hospitalized between January 2015 and December 2024. This study was con-ducted in the intensive care unit of China Medical University Hospital, Tai-chung, Taiwan. Twenty-three patients received levosimendan within 72 h, whereas the others did not receive an inodilator. Primary endpoints included ECMO weaning failure and the 90-day all-cause mortality rate. Kaplan-Meier survival curve analysis was also performed. Possible covariates for all-cause mortality were estimated using Cox regression modeling. Results The levosi-mendan group exhibited lower rates of ECMO weaning failure and 90-day all-cause mortality than the control group (13.0% vs. 52.6% and 17.4% vs. 57.0%, respectively; both p < 0.001). The 90-day survival curve analysis re-vealed that the levosimendan and control groups had survival rates of 0.83 and 0.43, respectively (log-rank p < 0.001). Administration of levosimendan within 72 h resulted in a hazard ratio of 0.30 (95% confidence interval: 0.12−0.75, p = 0.01). Conclusions Administering levosimendan within 72 h of ECPR could be a protective factor in improving all-cause mortality.
Article
Medicine and Pharmacology
Urology and Nephrology

Markus Angerer,

Christian Wülfing,

Klaus-Peter Dieckmann

Abstract: Introduction: Retroperitoneal lymph node dissection (RPLND) plays a crucial role in the staging and treatment of testicular cancer, and is often mandatory. RPLND is associated with a high risk of morbidity. The use of minimally invasive techniques have significantly increased the number of robotic procedures performed over the last few years. This study aimed to analyze the perioperative and postoperative outcomes and trends of an increasing number of surgeries performed. Materials and Methods: We retrospectively analyzed 30 robotic-RPLNDs (R-RPLND) performed at our testicular cancer center between 2020 and 2024. Logistic regression analyses were used to analyze the independent variables of operative time (OT), hospital stay (HS), estimated blood loss, lymph node yield, and complications according to the Clavien-Dindo classification system. The independent predictors included case number, clinical stage, post-chemotherapy status, preoperative retroperitoneal tumor mass, and body mass index. Furthermore, the patients were categorized into three groups: group A (cases 1-10), group B (cases 11-20), and group C (cases 21-30). A Kruskal-Wallis test was performed to assess differences among the groups concerning OT, HS, and lymph node yield. Results: OT significantly decreased with an increasing number of cases ( p <0.001), and HS was significantly affected by overall complications (p = 0.0006). There were two major perioperative complications (6.6%). No factors predicted overall complications or Clavien-Dindo grades I-II or III-V. The Kruskal-Wallis test showed a significant difference (p < 0.05) in OT and HS for group C. Conclusion: R-RPLND for GCT demonstrates a clear learning curve, with significant improvements in OT, HS, and complication rates as surgeons gain experience. Overall, the low complication rates for R-RPLND did not indicate predictive factors for perioperative or postoperative complications. RPLND presents promising potential as a safe and effective treatment for GCT, especially when performed by experienced surgeons in specialized centers.
Review
Medicine and Pharmacology
Neuroscience and Neurology

Laura Peña-Zelayeta,

Karen Delgado-Minjares,

Marcos Villegas Rojas,

Karen León-Arcia,

Alberto Santiago-Balmaseda,

Jesús Andrade-Guerrero,

Isaac Pérez-Segura,

Emmanuel Ortega-Robles,

Luis O. Soto-Rojas,

Oscar Arias-Carrión

Abstract: Parkinson’s disease encompasses a spectrum of motor and non-motor manifestations, with the latter often preceding motor symptoms and influencing disease trajectory. Sensory dysfunction, sleep-related disorders, autonomic impairment, neuropsychiatric symptoms, and cognitive decline reflect widespread neurodegeneration involving the brainstem, limbic system, and peripheral nervous system. Hyposmia and visual dysfunction are emerging as early biomarkers, while chronic pain and paraesthesias indicate central and peripheral nociceptive dysregulation. Sleep-related disorders, particularly REM sleep behaviour disorder and insomnia, frequently arise in the prodromal phase, highlighting disruptions in circadian regulation and neuroanatomical integrity. Neuropsychiatric symptoms—including depression, anxiety, apathy, and hallucinations—result from complex dysregulation of dopaminergic, serotonergic, and noradrenergic pathways, compounding disease burden and impairing quality of life. Autonomic dysfunction, affecting cardiovascular, gastrointestinal, thermoregulatory, and genitourinary systems, underscores the systemic nature of the disease. Despite growing recognition of these non-motor features, treatment strategies remain limited, constrained by a dopamine-centric therapeutic framework that does not fully address broader neurobiological dysfunction. The lack of reliable biomarkers hampers early diagnosis and precision medicine approaches, while the conventional dichotomy between motor and non-motor symptoms has hindered the development of integrative treatment paradigms. While previous reviews have examined individual non-motor manifestations in detail, this article provides a comprehensive synthesis, offering a clinically relevant perspective for medical students, primary care physicians, and non-specialists. Recognizing non-motor symptoms as core disease manifestations rather than secondary sequelae is essential to refine diagnostic criteria and develop targeted therapies. Parkinson’s disease is a complex, multisystem neurodegenerative disorder that necessitates a paradigm shift in research priorities and clinical management. A broader, integrative perspective is required to redefine how the disease is understood, taught, and treated, ensuring that motor and non-motor symptoms are addressed to improve patient outcomes.
Review
Medicine and Pharmacology
Pharmacy

Ashutosh Sengar

Abstract: Targeted drug delivery systems have become revolutionary in therapy with increased effectiveness and reduced side effects compared to traditional practice. Liposomal and nanoparticle carriers are among the very effective nanoplatforms with controlled delivery, site-directed drug concentration, and enhanced therapeutic outcomes. Transformation of drug delivery from traditional systems to nanocarrier systems is presented herein with emphasis on mechanisms, advantages, and medical applications. Liposomal nanocarriers are bioavailable and stable, while nanoparticles are tumor-specific drug delivery systems based on smart and responsive platforms. Eco-friendly and biodegradable materials in drug design also lead to drug safety and biocompatibility improvements.One of the key characteristics of modern nanomedicine is its ability to leverage the tumor microenvironment, and in particular the EPR effect, to deliver drug concentration in cancer tissue. Biological barriers, however, are problematic, and as such new strategies such as surface engineering and enzyme-sensitive nanoparticles must be used to increase penetration and therapeutic effect. Although these present some issues, long-term nanotechnology research can assist in improving drug delivery methods and treatment to become individualized and effective. The present review is a summary of existing innovation in liposomal and nanoparticle-based drug delivery, their role in precision medicine and the treatment of cancer, and how they have potential to revolutionize.
Article
Medicine and Pharmacology
Orthopedics and Sports Medicine

Amarildo Smakaj,

Umberto Tarantino,

Riccardo Iundusi,

Angela Chiavoghilefu,

Lorenzo Abbondante,

Chiara Salvati,

Chiara Greggi,

Elena Gasbarra

Abstract: The study aims to evaluate adherence to Romosozumab treatment in osteoporotic patients after surgical fracture fixation and compare side effects with non-fractured controls on the same therapy. This retrospective case–control study was conducted at the Orthopaedic Department of Policlinico Universitario di Roma “Tor Vergata,” following the principles of the Declaration of Helsinki. It included postmenopausal women aged over 60, with the case group receiving Romosozumab after fracture fixation, and the control group consisting of women on Romosozumab therapy without fracture fixation. Exclusion criteria included psychiatric conditions, contraindications to Romosozumab, high-energy trauma, or other bone metabolism disorders. Data on fractures, surgeries, FRAX scores, MOC values, and follow-up details were collected. Side effects, including nasopharyngitis and severe events like hypocalcemia, stroke, and myocardial infarction, were recorded. Adherence was assessed via pharmacy records and patient interviews. Statistical analysis was performed using descriptive statistics, t-tests, and chi-square tests. The study included 25 patients, with 12 in the surgical group and 13 in the conservative treatment group. The surgical group had a mean age of 67.3 years and a follow-up of 374 days, while the conservative group had a mean age of 76.4 years and a follow-up of 287 days. The surgical group underwent various fracture treatments, including femoral, humeral, and distal radius fractures, while the conservative group was treated with immobilization. There were no significant differences in FRAX scores or MOC values between the two groups. Vitamin D levels increased significantly in both groups after supplementation, but parathyroid hormone levels showed no difference. No new fractures occurred, and surgical patients had no delayed union or nonunion, though two had superficial wound infections. Both groups adhered well to Romosozumab therapy, with no severe side effects; minor side effects included myalgia in the surgical group and shoulder arthralgia in the conservative group. Romosozumab is well-tolerated and adherent in osteoporotic patients after osteosynthesis surgery, with adverse events similar to non-fractured individuals. While the study design is appropriate, multicenter trials would improve sample size and allow for subgroup analysis based on fracture type and demographics.
Review
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Manoj Mandal,

David Pires,

José Miguel Azevedo-Pereira,

Elsa Anes

Abstract: Despite continuous and extensive global efforts in the fight against tuberculosis (TB) this infectious disease continues to exert a tremendous burden on public health concerns and deaths worldwide. TB, caused by the bacterial species Mycobacterium tuberculosis is highly frequent in people living with HIV. The continuing epidemics with both chronic infections, and the emergence of antimicrobial resistance together with the lack of effective diagnostic tools and drug-drug interactions pose major challenges in the fight against these pathogens. Development of a wide range of host-directed therapies may have the potential to improve treatment outcomes, helping to alleviate the considerable morbidity and mortality associated with both infections. In this review, we discuss the identification and development of new host-directed strategies based on protease inhibitors and their clinical relevance as adjunctive treatment. In the context of therapeutic agents with novel mechanisms, selective protease inhibitors, including saquinavir (SQV) and cystatins (CstC and CstF) are valuable targets that may provide effective therapeutic solutions for control Mtb and HIV coinfection.
Article
Medicine and Pharmacology
Clinical Medicine

Wenwen Diao,

Ying Guo,

Yingying Zhu,

Shuting Yu,

Xingming Chen,

Xiaoli Zhu

Abstract: Objective: To enhance the awareness of the diverse manifestations of head and neck tuberculosis (HNTB) and the diagnostic hurdles it poses. Study Design: To analyze the presentation and clinical characteristics of HNTB cases. The diagnosis in all cases was established through histopathological examination of infected tissue in conjunction with medical history, TB-SPOT and other complementary TB investigations. Follow-up time 1 to 10 years. Setting: Peking Union Medical College Hospital. Methods: This retrospective study examined the clinical profiles of 60 patients diagnosed with HNTB at a tertiary university institution between 2013 and 2023.The cohort consisted of 29 men and 31 women aged 12 to 80 years (mean 43.95±16.98 years). Results: HNTB predominantly manifested in the larynx (27 cases, 45.0%), with most cases presenting with diffuse ulcerated or proliferative lesions. Notably, six patients exhibited irregular lesions on the unilateral vocal cords, mimicking early stage glottic carcinoma. The second most common localisation was in the cervical lymph nodes (20 cases, 33.33%), including cases such as retropharyngeal lymph node tuberculosis and tracheoesophageal groove lymph node tuberculosis. Conclusion: Clinicians should always consider HNTB in the differential diagnosis of lesions in this region. Given the oligobacterial nature of this disease and the absence of pulmonary involvement in the majority of cases, histopathological biopsy should be performed in cases of high suspicion. Early detection and treatment are of paramount importance to optimise therapeutic outcomes and improve the quality of life of patients.

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