Angiotensin II (Ang II) plays a role in several inflammatory diseases and is capable of inducing the release of inflammatory mediators in several cell types. The objective was to investigate the potential of Ang II to induce mRNA expression of inflammatory mediators by cultured primary human periodontal cells. A synergistic effect of a co-treatment with Ang II and IL1β on mRNA expression of inflammatory mediators was also explored. Primary cultures of human fibroblast-like cells isolated from gingival and periodontal ligament tissues from 3 subjects were established using explant techniques. Immunophenotyping of STRO-1, Ang II type 1 receptor (AT1R) and Ang II type 2 receptor (AT2R) was performed by flow cytometry analysis. Cell cultures were challenged with Ang II (1M) for 3, 6 and 24h with or without a co-treatment with IL1β (0.1ng/mL) for 24h. mRNA expression of inflammatory mediators was performed by real time quantitative polymerase chain reaction (RT-qPCR). We present, for the first time, a precise quantification for AT1R and AT2R on human gingival and periodontal fibroblast-like cell types; the percentage of positive immunostaining compared to the total population of cells varied from 3.35% through 5.29% for AT1R and 2.97% through 4.57% for AT2R. Ang II slightly upregulated mRNA expression of IL6 and CCL2/MCP1 in gingival cells and IL8 and PTGS2/COX2 in periodontal ligament cells. IL1β induced upregulation of IL8, IL6 CCL2/MCP1, PTGS2/COX2 and IL1β mRNA in both cell types. Co-treatment with Ang II and IL1β did not show a synergistic effect under these experimental conditions. Ang II shows a low potential to induce mRNA upregulation of inflammatory mediators in cultured primary human gingival and periodontal ligament cells, most likely due to the low percentage of Ang II receptors in such cells, and no synergistic effect with the co-treatment with IL1β.

Breast cancer-related lymphedema (BCRL) affects approximately 20% of women after breast cancer therapy. Advances in treatment have increased life expectancy, thus the prevalence of BCRL will continue to rise with the number of cancer survivors. Hence the need to develop strategies to prevent this condition. We provide a systematic review of the literature on primary prevention of BCRL by prophylactic lymphatic surgery (PLS). Between June and August 2022, we conducted a search of PubMed, Google Scholar and Cochrane. In the end a total of eighteen papers were selected. The eleven studies without a control group reported only 15 of 342 patients who developed lymphedema at least six months after PLS (4.59%). The seven studies with a control group included 569 patients, 328 cases and 241 controls. Among the cases, 36 (10%) developed lymphedema. In contrast, the incidence of lymphedema in controls was 40% (98 of 241 patients). Formulation of definite recommendations in favour of PLS is hindered by low-quality studies. There is no consensus on which technique should be preferred, nor on whether adjuvant radiotherapy might affect the efficacy of PLS. Randomized controlled trials are mandatory to conceive evidence-based recommendations.

Background: Parathyroid imaging techniques are used in patients with biochemically confirmed primary hyperparathyroidism (pHPT) to detect the localization of enlarged parathyroid gland(s) (PTG) and thereby to allow more focused, unilateral or minimally invasive parathyreoidectomy (PTX), instead of classical bilateral neck exploration (BNE). Although the preferred sequence of imaging continues to evolve, ultrasonography (US) is usually the first line modality, followed by 99mTc sestamibi parathyroid scan (SPS). However, both tests may have suboptimal localizing accuracy with considerable rate of non-localized cases. Therefore, more accurate four-dimensional computed tomography scan (4D-CT) has been employed for PTG imaging. Currently, there is a paucity of data evaluating the utility of 4D-CT in low case-load settings. Aim: To evaluate the impact of PTG imaging, using 4D-CT in conjunction with it’s intraoperatively displayed results, on the outcomes of surgical PTX. Our primary outcome was sensitivity of 4D-CT in comparison to US and SPS for preoperative PTG adenoma localization. The secondary outcomes were the need for redo surgery and morbidity. Additionally, the characteristics of surgical PTX, i.e. operative time, number of removed parathyroid glands, and rate of simultaneous thyroid surgery, were assessed. Methods: A single-center retrospective analysis of surgically treated patients with pHPT from 01/2010 to 01/2021 was conducted. Evaluation of impact of the preoperative imaging modalities on the results of surgical treatment was carried out. Results: During the study period 290 PTX were performed, 45 cases were excluded due to surgery for secondary, tertiary or recurrent HPT, or due to use of alternative imaging techniques; the remaining 245 patients were included in the study. US was carried out for PTG imaging in 236 (96.3%), SPS in 93 (38.0%), and 4D-CT in 52 patients (21.2%). The use of 4D-CT was associated with a significantly higher rate of successful localization of enlarged PTG (49 cases, 94.2%) compared to US and SPS (74 cases, 31.4%, and 54 cases, 58.1%, respectively). We distinguished between three groups of patients based on preoperative imaging: 1) PTG lateralization via US or SPS in 106 (43.3%) cases, 2) precise localization of PTG via 4D-CT in 49 (20.0%) patients, and 3) in 90 cases (36.7%) PTG imaging failed to localize enlarged gland. The group of 4D-CT localization had significantly shorter operative time, lower rate of simultaneous thyroid resections, as well as lower rate of removal of ≥2 PTG, compared to the other groups. The 4D-CT imaging was also associated with the lowest perioperative morbidity and with the lowest median PTH in one month follow-up; however, compared to the other groups, these differences were statistically not significant. Implementation of 4D-CT (since 01/2018) decreased the need for redo surgery (from 11.5% to 7.3%), and significantly increased the annual case load of PTX at our institution (from 15.3 to 41.0), compared to the period before 4D-CT diagnostics. Conclusions: 4D-CT imaging enabled to precisely locate almost 95% of enlarged PTG in patients with pHPT. Accurate localization and intraoperatively displayed imaging results are useful guides for surgeons in making PTX a faster and safer procedure in a low volume center.

Background: We assessed the pertinence of yearly updating the International Working Group on the Diabetic Foot (IWGDF) risk classification in people with diabetes by quantifying the changes in the risk group and its accuracy in identifying those developing an ulcer (DFU) in a primary care setting. Methods: In our retrospective cohort study, we included all people with diabetes with a foot as-sessment registry between January 2016 and December 2018 in the Baixo Alentejo Local Health Unit. Foot-related data was collected at baseline after one and two years. DFU and/or death until December 2019 were registered. The proportion of people changing their risk status each year was calculated. Accuracy measures of the IWGDF classification to predict DFU occurrence at one, two, and three years were calculated. Results: A total of 2097 people were followed for three years, during which 0.1% died, and 12.4% developed a DFU. After two years, 3.6% of the participants had progressed to a higher-risk group. The IWGDF classification presented specificity values superior to 90% and negative predictive values superior to 99%. Conclusion: Foot risk status can be safely updated every two years instead of yearly. The IWGDF classification can accurately identify those not at risk of DFU.

Heart failure (HF) affects about 60 million people worldwide, making it one of the chronic conditions with the greatest health and economic impact. The primary objective was to assess the efficacy of lung ultrasound (LUS) in the management of HF in order to intervene early and reduce the rate of hospital readmissions. A systematic search was conducted on PubMed, Embase, Google Scholar, Web of Science, and Scopus, including clinical trials, meta-analysis, systematic reviews, and original articles from 2019/1/1-2023/12/31, about LUS for the assessment of HF, on an outpatient basis, for HF diagnosis or/and decompensation. There may be risk of bias because the effects are dependent on the persons delivering the intervention. The results were synthetized by PRISMA method. A total of 873 articles were identified of which 33 articles were selected: [n=19] focused on prognostic assessment of HF, [n=11] centred on multimodal diagnostic assessments, and [n=2] addressing therapeutic guidance for HF diagnosis. LUS exhibits advantages in the detection of sub-clinical congestion linked to prognostic significance in re-admission and mortality during out-patient follow-up, after hospital discharge, and in complex scenarios as the patients' homes or institutional long-term care facilities. However, there are considerable uncertainties in their interpretation and monitoring changes due to its lack of standardization. The need for an updated international consensus on the use of LUS seems obvious.

Nutrient release from marine sediments in Osaka Bay has a significant impact on nutrient concentrations in seawater. A tsunami induced by the Nankai Trough earthquake may disturb marine sediments in the inner part of Osaka Bay. An incubation experiment to estimate the release rates of NH4-N and PO4-P was conducted to understand the present conditions and to quantify the changes caused by tsunamis. Two types of cores were created: a "control core" representing the current sediment, and a "redeposition core" representing the redeposition after the tsunami. The release rates have been decreasing since the year 2000 and have remained low. The experimental results suggest that the release rate after exposure to an aerobic environment by a tsunami may decrease to approximately 70% for NH4-N and 60% for PO4-P of the current level. In the past, the release rates were values experienced in the inner part of Osaka Bay. However, the reduction in the release rate by tsunamis may be more limiting for primary production under the current situation where the contribution of release for nutrients in seawater is significant.

End-stage heart failure (ESHF) leads to hypoperfusion and edema formation in the whole body and is accompanied by neurohormonal and immunological alterations. Orthotopic heart transplantation (HTX) has been used as a beneficial option for ESHF. Due to the shortage of donor hearts, the ideal matching and timing of donors and recipients has become more important. Our aim was to explore the relationship between the clinical outcome of HTX and the cytokine and apolipoprotein profiles of the recipient pericardial fluid obtained at transplantation after opening the pericardial sac. The clinical data and the interleukin, adipokine and lipoprotein levels in the pericardial fluid of twenty recipients were investigated. Outcome variables included primer graft dysfunction (PGD), need for posttransplantation mechanical cardiac support (MCS), International Society for Heart and Lung Transplantation grade ≥ 2R rejection and mortality. Recipient risk scores were also investigated. Leptin levels were significantly lower in patients with PGD than in those without PGD (median: 6.36 [IQR: 5.55-6.62]; versus 7.54 [IQR=6.71-10.44]; p = 0.029). Higher ApoCII levels (median: 14.91 [IQR: 11.55-21.30] versus 10.31 [IQR=10.02-13.07]; p = 0.042) and ApoCIII levels (median: 60.32 [IQR: 43.00-81.66] versus 22.84 [IQR=15.84-33.39]; p=0.005) were found in patients (n=5) who died in the first 5 years after HTX. In patients who had rejection (n=4) in the first month after transplantation, the levels of adiponectin (median: 74.48 [IQR: 35.51-131.70] versus 29.96 [IQR: 19.86-42.28]; p=0.039), ApoCII (median: 20.11 [IQR: 13.06-23.54] versus 10.32 [IQR: 10.02-12.84]; p=0.007) and ApoCIII (median: 70.97 [IQR: 34.72-82.22] versus 26.33 [IQR: 17.18-40.17; p=0.029) were higher than those in the nonrejection group. Moreover, the pericardial thyroxine (T4) levels (median: 3.96 [IQR: 3.49-4.46] versus 4.69 [IQR: 4.23-5.77]; p=0.022) were lower in patients with rejection than in patients who did not develop rejection. Our results indicate that apolipoproteins can facilitate the monitoring of rejection and could be a useful tool in the forecast of early and late complications.

Background Aspergillus spp. is a widely distributed filamentous fungus in the environment due to its high sporulation capacity. Currently, invasive aspergillosis (IA) is the most common invasive fungal infection in patients with hematologic malignancies with high rates of mortality and morbidity. The multifactorial nature of the disease requires appropriate risk stratification to allow the most appropriate preventive measures to be adapted and implemented according to the characteristics of the patient. In this sense, the present research aims to identify recent risk factors and environmental control measures against invasive aspergillosis to establish preventive actions to reduce the incidence of invasive aspergillosis in hospitals; (2) Methods: We conducted a qualitative systematic review of the scientific literature on environmental risk factors and preventive measures for invasive aspergillosis in patients with hematological malignancies. The Medline, Cochrane and Scopus databases were consulted, following the PRISMA and STROBE guidelines; (3) Results Adequate implementation of environmental control measures is presented as the most efficient intervention in terms of prevention to decrease the incidence of invasive aspergillosis in hospitals. We identify neutropenia, fungal contamination, lack of adequate environmental control measures in hospitals and patients´ homes, duration of hospitalization, and anemia as independent risk factors. We show that HEPA, LAF and Plasmair® systems are suitable methods to reduce the concentration of airborne fungal spores. Antifungal prophylaxis did not influence the reduction of IA significantly in our study; (4) Conclusions: Proper professional training and environmental control measures in hospitals are essential for the prevention of invasive aspergillosis. We should optimize risk stratification for patients with hematologic malignancies. Antifungal prophylaxis should be complementary to environmental control measures and should never be substituted for these last ones. Studies should also be done to evaluate the efficiency of environmental control measures against IA at patients' homes.

SpyGlass peroral cholangioscopy (POCS) has greatly improved the diagnosis of biliary strictures by allowing direct visualization and tissue sampling in the bile ducts. Supported by strong registry data and careful analysis, POCS is highly accurate in diagnosis and carries minimal risks. It plays a pivotal role in diagnosis of indeterminate biliary stricture like primary sclerosing cholangitis (PSC), which increases the risk of cancer. POCS facilitates early disease detection through distinctive endoscopic observations and provides essential information with directed biopsies that assess inflammation and potential malignancy. This case study showcased POCS's diagnostic ability when it accurately identified benign findings in a 59-year-old patient with jaundice. Treatment with ursodeoxycholic acid resulted in significant improvements, highlighting the diagnostic performance of POCS. In summary, POCS simplifies complex biliary stricture cases, expedites diagnosis and intervention, and significantly contributes to improving patient outcomes in challenging hepatobiliary conditions.

The elastic wave equation with the seismic tensorial force is solved in a homogeneous and isotropic medium (the Earth). Spherical-shell waves are obtained, which are associated to the primary P and S seismic waves. It is shown that these waves produce secondary waves with sources on the plane surface of a half-space, which have the form of abrupt walls with a long tail, propagating in the interior and on the surface of the half-space. These secondary waves are associated to the seismic mainshock. The results, previously reported, are re-derived by using Fourier transformations and specific regularization procedures. The relevance of this seismic motion for the ground motion, the seismographs' recordings and the effect of the inhomogeneities in the medium are discussed.

The late diagnosis of Type 2 Diabetes Mellitus can occur due to lack of access to the primary health care system and the non-manifestation of symptoms. Faced with this problem, this work presents the creation of a mobile application, called DiabetesCheck, for predicting the risk of Type 2 Diabetes Mellitus. A mathematical model is used, which classifies the risk of Type 2 Diabetes Mellitus for a group of patients with intervention and for a comparative group, using Fuzzy Classification and Decision Trees. The proposed application allows the health professional to monitor patients through the history stored in a database, allowing a representation of the evolution of patients and indication of medications. Therefore, this proposal aims to carry out the diagnosis in the initial phase of the disease and help in the prescription of more effective treatments and in the proposition of public policy strategies in epidemiology and screening.

Scholars and policymakers see sustainability as depending on the interrelationships between the three pillars of the environment, society and the economy. However, it remains less clear how key stakeholders with a responsibility for educating the next generation perceive the concept of sustainability and act accordingly. In order to gain new insights, this research scrutinises participant perceptions on sustainability and climate change in two eco-schools in England for primary children (aged 5-11 years). Our case study involved individual interviews with classroom teachers and headteachers, group interviews with fourth- and fifth-year students (ages 10-12 years), and in-class observations. We also analysed data from student exercise books and photographs of school grounds to understand participants’ self-reported knowledge and perceptions of sustainability and climate change. Within a framework drawing on theories of science communication and transformative learning (a learning approach based on having challenging experiences), the results show that the integration of sustainability into the curriculum was limited and problematic. That is despite the fact that all students and teachers were aware of the environmental dimensions of sustainability, like climate change and the overuse of natural sources. These findings suggest that schools are no different to other institutional settings when it comes to dealing with the challenges of integrating sustainability into daily practice. We conclude that there is a need for in-service teacher education programmes to enable and motivate teachers to provide richer teaching-learning environments so as to enable effective learning in schools about sustainability and climate change.

Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer and its treatment is hindered by resistance to targeted and immunotherapies and combinations ob both. We have reported that knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) with chemically-modified antisense oligonucleotides induces proliferative arrest and apoptotic death in tumor cells from many human and mouse cancer types. These studies have been mostly performed in vitro and in vivo on commercially-available cancer cell lines and have shown that, in mouse models, tumor growth is stunted by the treatment. The present work was performed on cells derived from primary and metastatic ccRCC tumors. We established primary cultures fom primary and metastatic ccRCC tumors, which were subjected to knockdown of ASncmtRNAs in vitro and in vivo in an orthotopic xenograft model in NOD/SCID mice. We found that these primary ccRCC cells are affected in the same way as tumor cell lines and, in the orthotopic model, tumor growth was significantly reduced by the treatment. This study on patient-derived ccRCC tumor cells represents a model closer to actual patient ccRCC tumors and shows that knockdown of ASncmtRNAs poses a potential treatment option for these patients.

High insertion torques increase the primary stability of dental implants, which might be beneficial for immediate loading protocols, but may lead to local ischemia and necrosis of the bone-implant interface. This study compared the outcomes of implants placed with low (<45Ncm), conventional(45-70Ncm), and high (≥75Ncm) insertion torques in All-on-4 concept cases with up to 2-year follow-up. Patients included in this study presented edentulous or partially dentate arches with an indication for full-arch rehabilitation. Implants were installed following the All on four protocol and were divided into 3 groups: Low, Conventional, and High torque, and were followed periodically for 2 years with ISQ measurements. The results showed no significant differences in success rates between the three groups. This suggests that high insertion torques may maintain higher primary stability values for immediately loaded implants during the healing period. Further studies are necessary to confirm these findings.

The prevalent pathogens associated with bovine uterine infections are bacteria that appear to increase the host's susceptibility to secondary infections with other bacteria or viruses, among which BoHV-4 is the most frequently found. In this work, the study of the pathways of apoptosis induction was carried out on an experimental model of primary culture of endometrial cells, in order to know the implication of BoHV-4 and the presence of bacterial LPS in the pathogenesis of the bovine reproductive tract. For this, different staining techniques and molecular analysis by RT-PCR were used. The results obtained allowed us to conclude that the level of cell death observed in the proposed primary culture is directly related to the time of viral infection and the presence of LPS in BoHV-4 infection. The apoptosis indices in cells infected with BoHV-4, BoHV-4 + LPS presented a maximum that correlates with the appearance of the cytopathic effect, and the maximum viral titers in the model studied. However, morphological, biochemical and molecular changes were evident during both early and late stages of apoptosis. These findings provide information on the factors that may influence the pathogenesis of BoHV-4 and help to better understand the mechanisms involved in virus infection.

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the results of traditional immunosuppressive therapy are disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients would eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and there is increasing evidence that gut microbiota and bile acids play an important role in cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Understanding the gut microbiota-bile acid network and corresponding immune functions in PBC provides a new perspective for its treatment strategies. Therefore, we summarize the latest advancements in research of gut microbiota and bile acids in PBC and, for the first time, explore the potential of immune factors related to them as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p>0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

Improving the quality and access to healthcare services in rural areas is fundamental to develop sustainable healthcare systems. This research aims to explore the motivations of healthcare professionals to work and settle in rural island areas of Greece with limited access to secondary and tertiary care. The study suggests practical ways to encourage self-motivation and attract more health workers in rural areas. An exploratory qualitative research approach was employed, involving semi-structured interviews with 16 healthcare professionals working in primary care units that lack direct hospital or hospital-health center access. The research was conducted specifically in the rural islands of Cyclades. Thematic analysis was conducted to identify common themes and unique insights from the participants. The analysis revealed three thematic categories. Τhe «attraction» thematic was influenced by personal factors, random selection, origin, accommodation factors, professional factors and obligatoriness. The «recruitment» thematic was associated with understaffing, special care issues, unstable working environment, educational and organizational aspects, and insular lifestyle. The thematic of «retention» highlighted personal issues, accommodation difficulties, economic and work-related issues, and unique challenges posed by an insular lifestyle. This research provides valuable insights into the motivations that drive healthcare professionals to settle, work, and remain in remote island units, as well as the challenges they encounter in making this decision. The study proposes strategies to motivate and attract more healthcare professionals to rural areas. These findings should be considered when formulating or reviewing primary healthcare empowerment policies to ensure equitable healthcare access for all individuals.

Cerebral cavernous malformations (CCM) or familial cavernomatosis is a rare, autosomal dominant, inherited disease characterized by the presence of vascular malformations consisting of blood vessels with an abnormal structure in the form of clusters. Based on the altered gene (CCM1/Krit1, CCM2, CCM3) and its origin (spontaneous or familial), different types of this dis-ease can be found. In this work we have isolated and cultivated primary endothelial cells (ECs) from peripheral blood of a type 1 CCM patient. Differential functional and gene expression pro-file of these cells were analyzed and compared to primary ECs from a healthy donor. The muta-tion of the familial index case consisted of a heterozygous point mutation in the position +1 splicing consensus between exons 15 and 16, causing failure in RNA processing and in the final protein. Furthermore, gene expression analysis by quantitative PCR revealed a decreased ex-pression of genes involved in intercellular junction formation, angiogenesis, and vascular ho-meostasis. Cell biology analysis showed that CCM1 ECs were impaired in angiogenesis and cell migration. Taken together, the results obtained suggest that the alterations found in CCM1 ECs are already present in the heterozygous condition, suffering from vascular impairment and someway predisposed to vascular damage.

The effects of statin use for primary prevention in reducing mortality among older adults in Asian populations are unknown. This study aimed to determine whether use of statins for primary prevention was associated with a decreased risk of all-cause mortality in a Japanese older adult population. A regional, population-based, longitudinal cohort study was conducted using the Shizuoka Kokuho Database (SKDB). Data were compared between the statin-treated group and a non-statin-treated (control) group using the inverse probability of treatment weighting (IPTW) method. In the SKDB cohort aged ≥65 years, new statin use was associated with a decreased risk of all-cause mortality (hazard ratio, 0.40; 95% confidence interval [CI], 0.33–0.48) after IPTW adjustment. The risk difference for mortality at 5 years in the statin-treated group (7.9%) compared with that in the control group (92.1%) was 0.05 (95% CI, 0.04–0.06), and the number needed to treat was 21.20 (95% CI, 18.10–24.70). In conclusion, statin use for primary prevention in older adults may reduce the risk of all-cause mortality in the population without atherosclerotic disease. Furthermore, statin use for primary prevention is feasible in patients aged 75 to <85 years and in patients with comorbidities such as diabetes, or dementia.

Background. Ovarian cysts are common in premenopausal women but can present with vague, non-specific symptoms, making discovery more challenging. Most are benign and resolve spontaneously; however, they can present, as in this case, as ovarian torsions, which is a gynecological emergency. Case presentation. A twenty-year-old female had presented over 3–4 times per year for the last 6 years to her primary doctor citing intermittent abdominal pain, irregular menstruation, dyspnea, and an enlarging abdomen circumference. The doctor stated, she was “just fat” and could, benefit from a “special camp to lose weight”, so she stopped mentioning her concerns. Upon presenting to the emergency department with acute onset abdominal pain, a computed tomography scan showed a large cyst lesion filling the abdominal and pelvic cavity. Its origin appeared to be from the left adnexa. Surgery was performed, and an acute ovarian torsion caused by a 36 cm craniocaudal left ovarian cyst was found and removed along with the left fallopian tube and 16 L of fluid. Conclusions. The value of respecting the “third presentation” rule indicates to health care providers that any patient who presents with any /or other symptoms or complaint needs to be thoroughly investigated. In this case the patient presented recurring pelvic/abdominal concerns, irregular menstruation, which warranted further investigation to safeguard fertility and prevent errors of omission. It is important to consider the differentials and be aware of vague symptoms that may lead to early recognition and effective management to prevent adverse consequences, complications, or even death.

Primary failure of eruption (PFE) is a rare non-syndromic condition involving total or partial non-eruption of posterior teeth, in the absence of mechanical obstruction. This paper presents the case of a healthy girl referred at age 4 years for asymmetry of upper arch. Clinical examination confirmed a slight shift of the upper midline to the left, with no erupted teeth distal to the upper left canine and left posterior open bite. Panoramic X-ray showed delayed intra-osseous development of lateral left upper teeth compared to the right side. Clinic and radiographic follow-up during the next 9 years showed that 26 has not erupted by almost 13 years of age, 27 has delayed development and an unusual shape and there is agenesis of 24, 25. Genetic analysis using the PTH1R single gene sequencing did not detect any known disease-causing or rare pathogenic variants that could explain the patient's phenotype. Even when detected early, PFE rises difficult problems with regard to diagnosis and ortho-surgical treatment planning due to the impossibility to accurately predict the evolution. Tooth agenesis on the same arch worsens the prognosis and adds challenges to planning the treatment. Close long-term follow-up and timely adjustment of treatment plan in accordance to the evolution of the case are needed.

Cholangiocellular carcinoma (CCA) is the second most common primary liver cancer, with increasing incidence worldwide and inadequate therapeutic options. Intra- and extrahepatic bile ducts have distinctly different embryonic origins and developmental behavior, and accordingly intra- and extrahepatic CCAs (ICC vs. ECC) are molecularly different. A promising strategy in oncotherapy is targeted therapy, targeting proteins that regulate cell survival and proliferation; such as the MAPK/ERK and PI3K/AKT/mTOR signaling pathways. Inhibitors of these pathways have been tested previously in CCA cell lines. However, these cell lines could not be clearly assigned to ICC or ECC, and results indicated apoptosis induction by targeted therapeutics. We tested targeted therapeutics (selumetinib, MK2206) in three defined ICC cell lines (HuH28, RBE, SSP25). We observed cooperative effects of dual inhibition of the two pathways, in accordance with inhibition of phospho-AKT and phospho-ERK1/2 expression. Proliferation was blocked more effectively with dual inhibition than with each single inhibition, but cell numbers did not drop below baseline. Accordingly, we observed G1-phase arrest, but not apoptosis (cleaved caspase-3, AIFM1 regulation, subG1-phase) or necroptosis (phospho-MLKL). We conclude that dual inhibition of MAPK/ERK and PI3K/AKT/mTOR pathways is highly effective to block proliferation of ICC cell lines, but therapy must certainly be supplemented with standard therapies.

The frequency of concurrent thyroid cancer in patients with primary hyperparathyroidism (pHPT) varies. While the pathological association between thyroid and parathyroid disorders is frequently noted, the co-occurrence of parathyroid adenoma and papillary thyroid cancer is exceptionally rare. Furthermore, the occurrence of an ectopic parathyroid adenoma in the retropharyngeal space is exceedingly rare. Ectopic parathyroid glands present considerable complexities in both diagnosis and surgical management, especially within the realm of surgical intervention. The potential inability to accurately identify and excise ectopic parathyroid adenomas during the initial surgery may lead to an increased morbidity and recurrence, requiring high-risk reoperations. Therfore, the evaluation of anatomical variations through the utilization of relevant diagnostic tools plays a crucial role in guiding decisions pertaining to clinical manifestations, diagnostic methods, surgical interventions, and operative strategies for parathyroid tumors. We present the case of a 51-year-old female patient with papillary thyroid carcinoma in the right thyroid lobe and an ectopic parathyroid adenoma in the retropharyngeal space confirmed through surgical intervention. This case sheds light on the unusual occurrence of an ectopic parathyroid adenoma in the retropharyngeal region within a thyroid cancer patient, providing valuable insights within the realm of thyroid malignancies.

Chronic Mesenteric Ischemia (CMI) arises from the inability to achieve adequate intestinal blood flow after meals, leading to an imbalance between oxygen and metabolite supply and demand. The true incidence of CMI remains uncertain. However, the occurrence of mesenteric artery occlusive disease (MAOD) is relatively common among the elderly population. Delays in diagnosing CMI can often be attributed to several factors, including the variability of patient symptoms, the range of potential causes for chronic abdominal pain with weight loss. Mikkelson pioneered the introduc-tion of a surgical treatment for occlusive lesions of the superior mesenteric artery (SMA) in 1957. The inaugural performance of endovascular revascularization (ER) for visceral vessels took place in 1980. The literature has documented two types of endovascular revascularization (ER) methods: percutaneous transluminal angioplasty (PTA) and primary stenting (PMAS). Despite the limited quality of available evidence, the consensus among experts is strongly in favor of PMAS over PTA alone for the treatment of atherosclerotic mesenteric artery stenosis. There are several key areas of focus for chronic mesenteric ischemia (CMI) treatment. Randomized controlled trials comparing different stent types, such as covered stents versus bare metal stents, are needed to evaluate effi-cacy, patency rates, and long-term outcomes in CMI patients.

Primary bone lymphoma of the scapula is a rare tumor that usually causes local pain. Presented patient suffered for two years from paresthesia, tingling, numbness, and edema of the little and ring finger. The 45-year-old man underwent several radiological and neurological assessments of the palm, elbow and neck prior to radiographs revealing the tumor of the left shoulder. Once diffuse large B cell lymphoma was confirmed, immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and methylprednisolone (R-CHOP) started. The treatment was accompanied by antiviral treatment with lamivudine due to positive hepatitis B virus serology and with bisphosphonate treatment for the prevention of bone resorption. Once immunochemotherapy was finished, the treatment was supplemented by radiotherapy of the shoulder. After more than three years of accomplishing remission, the patient had an ischemic stroke manifesting with right-sided hemiparesis. Following the physical therapy, the patient is currently in the process of evaluation for thrombophilia, as well as further cardiac assessment due to the positive transcranial Doppler bubble test setting high suspicion for the presence of patent foramen ovale.

The effects of chemical composition and solidification rate on the solidification behavior of high-Cr white irons were investigated through directional solidification. Increasing the solidi-fication rate in hypoeutectic alloys caused the finer dendrite arm spacing as expected. The eutec-tic structure which formed in the interdendritic region comprised of M7C3 and austenite, how-ever, secondary dendrite arms of hypoeutectic alloys contained a few M7C3 particles that solidi-fied prior to the eutectic structure. The transition from cellular to dendritic solidification oc-curred at a solidification rate between 50 µm/s and 100 µm/s in a near eutectic alloy. In the near eutectic alloy with cellular solidification, a directionally arrayed in-situ composite of M7C3/austenite formed within the cell. Speckle-like feature appeared in the intercellular region due to M23C6 carbide precipitation during subsequent cooling after freezing. Like dendrite arm spacing in hypoeutectic alloys, the inter-speckle spacing and the inter-fibre spacing became finer with increasing solidification rate in the cellular solidification range.

To date, the patent foramen ovale (PFO) does not get the deserved medical attention. The PFO poses a serious threat to health and even life of mankind. The first respective case report in the medical literature dates back to the 19th century. It led to death. The fact that a PFO is present in roughly 25% of people underscores its overall potential to do harm. Yet at the same time by the sheer number, it discourages the medical community from screening for it and from treating it. About 5% of the population have particularly dangerous forms of PFOs. Such PFOs portray a high enough risk for clinical events, the likes of death, stroke, myocardial infarction, or ocular, visceral, and peripheral embolism, to justify screening for them. Highly significant health incidents being at stake, it appears obvious that PFO closure should be used for primary prevention. This is supported by the fact that closing a PFO is the simplest intervention in cardiology, with presumably the highest clinical yield. Being mainly a preventive measure, PFO closure represents a mechanical vaccination. When closing PFOs for one of the rarer therapeutic indications (migraine, platypnea orthodeoxia, etc.), patients automatically profit from the collateral benefit of getting at the same time mechanically vaccinated for life against paradoxical embolism. Vice versa, closing a PFO for prevention of paradoxical embolism not infrequently betters or cures migraine or exercise dyspnea, thereby improving quality of life as a collateral benefit.

Background. Primary Stabbing Headache (PSH) is characterized by brief, focal and paroxysmal pain (“stab”), occurring sporadically or in clusters. Data on pediatric cases are poor. Methods. We performed a comprehensive literature review searching Pubmed, Cochrane and Embase in order to collect pediatric case reports and case series of PSH. Results. Twelve out of 162 articles assessed for eligibility were finally included. Prevalence of PSH and probable PSH varies from 2.5 to 10% among children with primary headaches and it is higher among children aged less than 6 years old. The mean age of onset is between 7 and 11 years of age. Attack duration greatly varies, ranging from a few seconds to several minutes. Intensity of pain is usually from moderate to severe. Associated symptoms are infrequent but may be observed (mainly photophobia, vertigo, nausea and vomiting). Neuroradiological findings are usually unremarkable; EEG may show sporadic epileptiform abnormalities (up to 30% of cases). Preventive therapy is anecdotal, including treatment with indomethacin, trazodone, valproate and amitriptyline. Conclusion: PSH is a common but still underdiagnosed entity among children with primary headache; further and larger cohort studies are needed to better assess, in particular, prognosis and response to therapy.

The KOSovan Acute Coronary Syndrome (KOS-ACS) Registry is established as a prospective, continuous, nationwide, web-based registry that is operated online. The KOS-ACS registry is designed with the following objectives: 1) to obtain data on the demographic, clinical, and laboratory characteristics of ACS patients treated in Kosovo; 2) to create a national database with information on health care in ACS patients treated in Kosovo; 3) to identify the national features of associations between ACS characteristics and clinical outcomes, including mortality, complications, length of hospital stay, and quality of clinical care; and 4) to propose a practical guide for improving the quality and efficiency of ACS treatment in Kosovo. The Kosovo Society of Cardiology and University of Prishtina will be responsible for the development of the KOS-ACS registry and centralized data analysis at the national level. The KOS-ACS Registry will enroll all patients admitted, at any of the registered clinical centers, with the diagnosis of ACS and who will be clinically managed at any of the Kosovo hospitals. Data on patient demographics, clinical characteristics, previous and hospital drug treatment, and reperfusion therapy will be collected. The type of ACS (Unstable angina, NSTEMI or STEMI) will also be clearly defined. The time from first medical contact to balloon inflation (FMC-to-balloon) and door-to-ballon time will be registered. In-hospital death and complications will be registered. Data on post-hospital primary outcome (MACE: cardiac death, all-cause mortality, hospitalization, stroke, need for coronary revascularization) of patients, at 30 days and 1 year, will be included in the Registry.

This cross-country four-year longitudinal study investigated the development of processing speed throughout primary school education. The analyses were conducted on data collected from 441 schoolchildren in Grades 1, 2, 3 and 4 (aged 6.42 to 11.85 years) in the Kyrgyzstan and Russia. Mixed effects growth modeling was applied to estimate average and individual growth trajectories for processing speed at two cross-country samples. Latent class growth modeling was conducted to identify different types of growth trajectories for processing speed and to compare the distribution of the types within the analyzed samples. According to the results, processing speed significantly increases across primary school years. The trajectory is characterized by nonlinear changes with more intensive growth between Grades 1 and 2, which later slows down until Grade 4. There were no significant cross-country differences in the initial score of processing speed or developmental changes in processing speed across primary school years. The development of processing speed is described by a model with three quadratic growth types but minimally differs. It is concluded that in both samples, the development of processing speed may be characterized by homogeneity, with the most intensive growth from Grade 1 to Grade 2 and subsequent linear improvement until Grade 4.

A homogenization of billets from Al-Cu-Li-Mg-Sc-Zr alloys should be accomplished at high annealing temperatures exceeding 500 °C. This type of aluminum alloy is susceptible to the depletion of surface layers from Li. Therefore, choosing a suitable homogenization temperature and duration is a crucial step in assuring a homogeneous distribution of alloying elements and optimal exploitation of the potential of the alloy. In-situ heating in an electron microscope was performed on a twin-roll cast Al-Cu-Li-Mg-Sc-Zr alloy to understand the peculiarities of the homogenization process. Four types of primary phase particles rich in Cu, Li, Mg, and Fe were identified in the as-cast material. They appear as coarse particles at the boundaries of eutectic cells. Their partial dissolution occurs at temperatures above 450 °C. They are almost fully dissolved at 550 °C, except for complex phases containing Fe and Cu. Small dimensions of eutectic cells in the range of 10 µm assure a homogeneous distribution of main alloying elements within the matrix after 20 min of annealing. Direct comparison with the same material prepared by mold-casting indicates that such short annealing times result in the dissolution of main primary phase particles but do not assure a homogeneous distribution of alloying elements in the whole volume of the specimen.

Milroy's disease (MD), also known as hereditary lymphedema type I, is a rare autosomal dominantly inherited primary lymphedema. It accounts for approximately twenty percent of all primary lymphedemas. MD typically presents clinically with bilateral lower extremity lymphedema. Our case report is about a rare case of MD presenting with unilateral lymphedema in both upper and lower extremities in a patient admitted to our clinic. A 24-year-old woman who had been under observation for lymphedema since she was 8 years old was diagnosed with MD by physical examination, venous Doppler ultrasound, whole body lymphoscintigraphy, and molecular genetic testing in our clinic, and partial improvement was achieved with Complete Decongestive Therapy, the gold standard treatment for lymphedema. Genetic counseling services may be especially useful for the patient and family. Although MD is rarely seen in the literature, many more studies are needed to identify carrier variants in the community.

Globally, cancer is an important health problem worldwide, and has become one modern medicine’s most serious problems to prevent, diagnose, and treat. Many types of cancers still have non-negligible mortality rates, and new treatments need to be developed for them. This study aimed to elucidate cancer mechanisms and facilitate cancer treatment and prevention. The ideal temperature for cancer growth is 35°C; however, conditions were not consistent with chromosomal instability, loss of alleles of tumor-suppressor genes, abnormal DNA methylation, and collagen phagocytosis, which are known causes of cancer. In addition, when cancer develops, white blood cells attack the cancer tissue and remove it; however, as the decrease in body temperature drops, leads to a reduction in the immune potential of the white blood cells. Based on previous papers, this study focused on aimed to determine the effects of the low-temperature environment of 35°C, the temperature at which cancer is most likely to proliferate, and changes in adenosine triphosphate (ATP) levels. The study revealed that Therefore, the causes of cancer is caused by include chromosome fusion that occurs occurring due to the impaired DNA topoisomerase IIα proliferation and primary cilia rotation due to resulting from decreased intercellular adhesion.

In this communication, we present a new simulated in situ lab/on-deck incubator, light spectrum replicator (LSR), and method to simulate the measured in situ HOCR light spectrum curves in incubation chambers. Carbon flux studies require detailed knowledge of primary and secondary production, including an understanding of temporal and spatial scales of variation. Interpretation of the processes involved during measurements continues to be difficult [1] since the incubation of the samples does not permit the study of rapid variations in carbon assimilation. Further, the significance of Dissolved Organic Matter of DOM in primary production is gaining attention as many autotrophic species are known for using organic substrates for growth, even in the dark [2–4] and since a significant portion of DOM can be accounted for from active release of intracellular metabolites by microbial consortia [5]. On the other hand, the major uncertainties in bacterial production measurements lie with the conversion factors used to calculate bacterial production (BP). For a given thymidine incorporation rate, estimates of BP can range by a factor of more than 20 [6,7]. Even though various new analytical tools have emerged [8], understanding of complex patterns of interactions within the microbial loop remains an open question.

Consuming fish sustainably means consuming less and better, considering environmental, social, and economic impacts. This demands more knowledge to make informed decisions. In this study, the main goal was to understand how sustainability education can be used as a tool to raise awareness and promote new habits regarding the sustainable consumption of fish in 4th-grade students at primary school. During the COVID-19 pandemic, face-to-face and online learning methodologies were used in two different groups of students to understand whether the teaching method impacted learning. A sequential explanatory mixed methodology was applied, with a pre-test/post-test design, combined with focus group sessions. Between the pre and post-tests three learning modules were performed. The results showed that the students were unaware of many aspects related to fish sustainable consumption, but the developed activities significantly increased their knowledge of the subject and impacted students to change their consumption behaviours. It was also found that the construction of knowledge by the students after the activities was achieved either by face-to-face or online learning. Interviews from focus group sessions showed that students got to know new fish species, learned about the concept of minimum landing size and closure season and that fish are labelled like other types of food.

Soil extracellular enzyme activity (EEAs) and enzymatic stoichiometry (ES) can provide a crucial indication of changes in soil ecosystem's nutrient availability and the microbial resource limitations. However, the changing characteristics of soil EEAs and ES at different stages of the native succession process and their key drivers are unclear. In order to investigate the soil EEAs, ES and driving factors of soil under vegetation at different succession stages, we adopted the "spatio-temporal substitution" method to collect the surface soil of bryophyte community, herbaceous community, shrub community and tree community in the new volcanic lava platform of Wudalianchi Volcanic Nature Reserve. We measured seven soil EEA, including carbon(C)-acquiring enzyme (β-1,4-glucosidase (BG)), N-acquiring enzymes (β-N-acetyl-glucosaminidase (NAG) and leucine aminopeptidase (LAP)) and phosphorus (P)-acquiring enzyme (acid phosphatase (AP)) activities. The length and angle of vectors defined by ratios of enzyme activities (BG/(NAG + LAP) vs. BG/AP) were used to indicate relative microbial investments in C- (length), and N- and P- (angle) acquiring enzymes. Our results showed that the contents of TC, TN, TP, MBC, DOC and NO3-N in shrub community soil were significantly higher than those in bryophyte, herb and tree communities, and increased by 441%, 246%, 137%, 5570%, 12% and 484%, respectively. The highest soil EEA of C-, N- and P-acquiring were found in shrub community, and the soil EEAs/MBC of C-, N- and P-acquiring were the highest in bryophyte community. Enzyme C:N, C:P and N:P ratios increased progressively in the order of bryophyte, herb and shrub community, but the enzyme C:N, C:P and N:P ratios of tree community were both far less than shrub community. Vector lengths increased progressively in the order of bryophyte (1.16), herb (1.27), tree (1.29) and shrub (1.40), and Vector angles decreased progressively in the order of bryophyte (49.15°), herb (45.65°), Tree (45.31°) and shurb (44.54°), suggested that as succession progresses, soil microbial nutrients transforms from P limitation (angle＞45°) to N limitation (angle＜45°). Redundancy analysis showed that TC, TN, EC and C:N were important drivers of variation in soil EEAs and ES in vegetation at different succession stages. Our findings highlight that the primary succession process cause nutrient limitation transformation. Soil ES might be a sensitive indicator mediated by soil microorganisms to the relative resource limitation at different stages of the primary succession process.

The global issues of overweight and sedentary lifestyles demand comprehensive responses from health systems, yet health education still needs to be more cohesive and less sporadic. This study focuses on primary school children as a specific target for instilling healthy habits, employing ac-tive learning strategies to address healthy diet and physical activity. Through Problem-Based Learning projects, the study engaged fourth-grade primary students in acquiring healthy habits. The study was carried out over four consecutive years at a school with two lines, allowing the employment of an opportunity sample and evaluating intervention and control groups by com-paring their corresponding scores. Control groups integrated a total of 54 students, while the in-tervention group included a total of 159 students. A pre-test and post-test questionnaire were used for data collection. Evaluation differential scores revealed statistically significant higher scores in the intervention groups: 3.62 points in control groups and 6,94 in intervention groups, particu-larly in attitudinal competences. These strategies not only facilitated the development of crucial skills such as information search, synthesis, representation, analysis, decision-making, teamwork, and intrapersonal awareness but also significantly broadened the knowledge acquired in aspects related to healthy habits. This approach proved effective in helping children comprehend the im-portance of healthy choices and encouraged integrating such habits into their daily lives.

Portal myofibroblasts (PMF) are known to be critical in bile duct injury, but their role in liver fibrogenesis remains underexplored. Thy-1, an adhesion molecule integral to fibroblasts, relevant in fibrogenesis and detectable in serum as soluble Thy-1 (sThy-1), is expressed by PMF but not hepatic stellate cells in vitro. This study aimed to elucidate the correlation between Thy-1 expression in liver histology and sThy-1 levels in serum with the degree of liver fibrosis in patients with primary biliary cholangitis (PBC) and metabolic dysfunction associated steatotic liver disease (MASLD). Liver histology samples were stained for Thy-1 and sThy-1 was measured using an enzyme-linked immunosorbent assay (ELISA). In patients with PBC and MASLD, portal Thy-1 expression significantly correlated with increased fibrosis. The sinusoidal Thy-1 expression also significantly correlated with increased fibrosis in patients with PBC (p

The aim of this study was to compare the effect of using L-PRF in patients undergoing impacted lower third molar surgery with either primary or secondary closure techniques. Methods: This prospective, randomised, double-blind, split-mouth clinical trial was conducted in patients with bilateral lower impacted third molars of similar position. Primary closure was performed in group 1 and secondary closure in group 2. Group 1 closure technique was applied to one side of the patients and group 2 closure technique was applied to the other side at different times. Nine pa-tients were excluded from the study due to alveolitis and failure to attend regular control visits out of the 45 patients evaluated. Results: Of the 36 patients included in the study, 23 were female and 13 were male and the mean age was 22.42±3.36 years. The secondary closure group had lower VAS scores at hour 6 (p

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment ele-vation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued. Out-of-hospital car-diac arrest and cardiogenic shock remain a major cause of high in-hospital mortality, whilst the growing burden of heart failure in long-term STEMI survivors presents a growing problem. Many elements aiming to optimize STEMI treatment are still subject to debate or lack sufficient evidence. This review provides an overview of the most contentious current issues in pPCI in STEMI patients, with an emphasis on unresolved questions and persistent challenges.

Introduction: Alzheimer's disease (AD) is the first cause of dementia worldwide without any current curative treatment. Facing an increasing prevalence and its associated costs, AD represents a public health challenge. Usual diagnostic methods still rely on extended interviews and paper tests provided by an exterior examiner. We aim to create a novel, quick cognitive-screening tool on a numerical tablet. Methods: This program, built and edited with Unity®, runs on Android® for the Samsung Galaxy Tab S7 FE®. Composed of seven tasks inspired by the Mini-Mental Status Examination and the Montréal Cognitive Assessment, it browses several cognitive functions. The architectural design of this tablet application is distinguished by its multifaceted capabilities, encompassing not only seamless offline functionality but also a mechanism to ensure the singularity of data amalgamated from diverse sites. Additionally, a paramount emphasis is placed on safeguarding the confidentiality of patient information in the healthcare domain. Furthermore, the application empowers individual site managers to access and peruse specific datasets, enhancing their operational efficacy and decision-making processes. We performed a preliminary usability assessment among healthy subjects. Results: 24 healthy patients were included with a final F-SUS score of "excellent". Participants perceived the tool as simple to use and achieved the test in a mean time of 142 seconds. No technical errors occurred. Conclusion: These preliminary results suggest that our new assessment on a numerical tablet allows a short cognitive screening.

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous hu-mour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side ef-fects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor β (TGFβ) in the anterior segment of the eye. Understanding how TGF affects both the structural and functional changes in the outflow pathway and IOP is required to de-velop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study we evaluated the effects of TGF-1 and -2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are pre-sented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in net-works to control cellular pathways and processes, a pathway-centric view of miRNA ac-tion is also reported. Evaluating TGF-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.

Primary ciliary dyskinesia (PCD) is caused by pathologic variants in over 50 different genes that affect the structure and function of motile cilia. Low nasal NO (nNO) is a biomarker for diagnosis in patients with features of PCD; but the reason why it is low is unclear. At the cellular level, a characteristic feature shared by most PCD patients is that antigens and other particles are not cleared from the epithelial surface. Poor antigen clearance results in pro-oxidant pathway activation and airway epithelial damage and may predispose PCD patients to DUOX1- and IL33- mediated asthma. Secondary ciliary dysfunction, such as that caused by viruses or by smoking, can also contribute to asthma development. Variants in genes underlying the function of cilia, can be associated with poor lung function, even in the absence of PCD. Single nucleotide polymorphisms in PCD – related genes can be associated with increased asthma severity. The role of cilia and antigen stasis is the pathophysiology of asthma is an important area for research, because specific airway clearance techniques and other therapeutic interventions, such as antioxidants, could be of value in preventing the development of asthma and asthma-like symptoms.

The platelet count, a component of the full blood count, has been identified as a useful diagnostic marker for cancer in primary care. The reference range for the platelet count is 150 to 400 or 450 × 109/l; this range does not account for natural variation in platelet count by age and sex. This study used three primary care cohorts from England Canada, and Australia. Patients aged 40 years and over with a full blood count were included and stratified by age (in 10-year bands), sex, (male/female), and platelet count group. Cancer incidence within one year of test date was estimated from linked registry data. In all three countries there was a clear upwards trend in cancer incidence with increasing platelet count, for both sexes and at all age groups. Lung and colorectal were the most common sites. These results have important implications for the international application of this work; analysis of local health datasets will be crucial to determine appropriate thresholds. Appropriate upper thresholds will depend on local populations, healthcare needs, and priorities. Further research is needed to assess the likely impact of new recommendations on the healthcare system, on cancer outcomes, and patient benefit.