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    Effect of distinct storage space conditions about COVID-19 RT-PCR results.

    Health care image resolution education and learning options pertaining to jr physicians along with non-radiologist specialists: An assessment.

    In prostate cancer, accurate diagnosis and grade group (GG) decision based on biopsy findings are essential for determining treatment strategies. Diagnosis by experienced urological pathologists is recommended; however, their contribution to patient benefits remains unknown. Therefore, we analyzed clinicopathological information to determine the significance of reassessment by experienced urological pathologists at a high-volume institution to identify factors involved in the agreement or disagreement of biopsy and surgical GGs. In total, 1325 prostate adenocarcinomas were analyzed, and the GG was changed in 452/1325 (34.1%) cases (359 cases were upgraded, and 93 cases were downgraded). We compared the highest GG based on biopsy specimens, with the final GG based on surgical specimens of 210 cases. The agreement rate between the surgical GG performed and assessed in our institute and the highest biopsy GG assessed by an outside pathologist was 34.8% (73/210); the agreement rate increased significantly to 50% (105/210) when biopsy specimens were reevaluated in our institute (chi-square test, P  less then  0.01). Multivariate logistic regression analysis showed that only the length of the lesion in the positive core with the highest GG in the biopsy was a significant factor for determining the agreement between biopsy GG and surgical GG, with an odds ratio of 1.136 (95% confidence interval 1.057-1.221; P  less then  0.01). Thus, reassessment by experienced urological pathologists at high-volume institutions improved the agreement rate. However, it should be noted there is a high probability of discordance between a small number of lesions or short lesions and surgical GG.Polymorphism of the major histocompatibility complex (MHC), DAB1 gene was characterized for the first time in the European bitterling (Rhodeus amarus), a freshwater fish employed in studies of host-parasite coevolution and mate choice, taking advantage of newly designed primers coupled with high-throughput amplicon sequencing. Across 221 genotyped individuals, we detected 1-4 variants per fish, with 28% individuals possessing 3-4 variants. We identified 36 DAB1 variants, and they showed high sequence diversity mostly located within predicted antigen-binding sites, and both global and codon-specific excess of non-synonymous mutations. Despite deep divergence between two major allelic lineages, functional diversity was surprisingly low (3 supertypes). Overall, these findings suggest the role of positive and balancing selection in promotion and long-time maintenance of DAB1 polymorphism. Further investigations will clarify the role of pathogen-mediated selection to drive the evolution of DAB1 variation.

    The aim of the study was to assess DWI with ROI-ADC and WL-ADC measurements in early response after NAC in breast cancer.

    Between January 2016 and December 2019, 55 women were enrolled in this prospective single-center study. MRI was performed at three time points for each patient before treatment (MRI 1 DW and DCE MRI), after one cycle of NAC (MRI 2 noncontrast DW MRI), and after completion of NAC before surgery (MRI 3 DW and DCE MRI). ROI-ADC and WL-ADC measurements were obtained on MRI and were compared to histology findings and to the RCB class. Patients were categorized as having pCR or non-pCR.

    Among 48 patients, 9 experienced pCR. An increase of ROI-ADC between MRI 1 and 2 of more than 47.5% had a sensitivity of 88.9% and a specificity of 63.4% in predicting pCR, whereas WL-ADC did not predict pCR. An increase of ROI-ADC between MRI 1 and 2 of more than 47.5% had a sensitivity of 83.3% and a specificity of 64.9% in predicting radiologic complete response. An increase of WL-ADC between MRI 1 and 2ecificity of 63.4% in predicting pCR, and a sensitivity of 83.3% and a specificity of 64.9% in predicting radiologic complete response. • A significant increase in breast tumor ROI-ADC at DWI predicted complete pathologic and radiologic responses.

    This study investigated the utility of temporal subtraction computed tomography (TSCT) obtained with temporal bone high-resolution computed tomography (HRCT) for the preoperative prediction of mastoid extension of middle ear cholesteatomas.

    Twenty-eight consecutive patients with surgically proven middle ear cholesteatomas were retrospectively evaluated. The presence of black color in the mastoid region on TSCT suggested progressive changes caused by bone erosion. Enlarged width of the anterior part of mastoid on HRCT was interpreted as suggestive of mastoid extension. Fisher’s exact test was used to compare the widths and black color on TSCT for cases with and without mastoid extension. The diagnostic accuracy of TSCT and HRCT for detecting mastoid extension and interobserver agreement during the evaluation of black color on TSCT were calculated.

    There were 15 cases of surgically proven mastoid extension and 13 cases without mastoid extension. Patients with black color on TSCT were significantly more li extension. •TSCT obtained with preoperative serial HRCT of the temporal bone is useful for assessing mastoid extension of middle ear cholesteatomas.

    This study was designed to evaluate the performance of high-resolution magnetic resonance imaging (HR-MRI) in detecting giant cell arteritis (GCA), evaluate superficial extracranial artery and other MRI abnormalities, and compare three-dimensional (3D) and two-dimensional (2D) techniques.

    PubMed, Web of Science, and Cochrane Library were screened up to March 7, 2021, and further selection was performed according to the eligibility criteria. Quality Assessment of Diagnostic Accuracy Studies-2 was used for quality assessment, and heterogeneity assessment and statistical calculations were also performed.

    In total, 1851 records were retrieved from online databases, and 15 studies were finally included. Regarding the performance of HR-MRI, the superficial extracranial artery had 75% sensitivity and 89% specificity, respectively, with an area under the receiver operating characteristic curve (AUC) of 0.91. Positive and negative post-test possibilities were 86% and 20%, respectively, with clinical diagnosis as reference. When referenced with temporal artery biopsy, the sensitivity was 91%, specificity was 78%, AUC was 0.92, and positive and negative post-test possibilities were 78% and 10%, respectively. 3D HR-MRI and 2D HR-MRI had 70% and 72% sensitivity, respectively, and 91% and 84% specificity, respectively.

    HR-MRI is a valuable imaging modality for GCA diagnosis. It provided high accuracy in the diagnosis of GCA and played a potential role in identifying GCA-related ischemic optic neuropathy. 3D HR-MRI had better specificity than 2D HR-MRI.

    HR-MRI helps clinicians to diagnose GCA. Superficial extracranial arteries and other MRI abnormalities can be assessed with HR-MRI. HR-MRI can help in assessing GCA-related optic neuropathy.

    HR-MRI helps clinicians to diagnose GCA. Superficial extracranial arteries and other MRI abnormalities can be assessed with HR-MRI. HR-MRI can help in assessing GCA-related optic neuropathy.

    Accurate prediction of portal hypertension recurrence after transjugular intrahepatic portosystemic shunt (TIPS) placement will improve clinical decision-making.

    To evaluate if perioperative variables could predict disease-free survival (DFS) in cirrhotic patients with portal hypertension (PHT) treated with TIPS.

    We recruited 206 cirrhotic patients with PHT treated with TIPS, randomly assigned to training (n = 138) and validation (n = 68) sets. We recorded 7 epidemiological, 4 clinical, and 9 radiological variables. TIPS-distal end positioning (TIPS-DEP) measured the distance between the distal end of the stent and the hepatocaval junction on contrast-enhanced CT scans. In the training set, the signature was defined as the random forest for survival algorithm achieving the lowest error rate for the prediction of DFS which was landmarked 4weeks after the TIPS procedure. In the training set, a simple to use scoring system was derived from variables selected by the signature. The primary endpoint was to asg DFS. • TIPS-DEP < 6mm was associated with a DFS probability of 78% at 6.5months post-landmark. • A simple scoring system calculated using age, Child-Pugh score, and TIPS-DEP predicted DFS after TIPS.

    • TIPS-DEP measurement was the third most important but only actionable variable for predicting DFS. • TIPS-DEP  less then  6 mm was associated with a DFS probability of 78% at 6.5 months post-landmark. • A simple scoring system calculated using age, Child-Pugh score, and TIPS-DEP predicted DFS after TIPS.

    Lumasiran, a sub-cutaneous RNA-interference therapy, has been recently approved for primary hyperoxaluria type 1 (PH1), with doses and intervals according to body weight. Little is known as to its use in infants; the aim of this study was to describe treatment outcome in 3 infants who received lumasiran therapy before 2years of age.

    Patient 1 was diagnosed antenatally and received lumasiran from day 9. According to the product information template (PIT), he received monthly lumasiran (3 times at 6mg/kg, then 3mg/kg), with hyperhydration and potassium citrate. Despite decreased plasma oxalate levels, persistent normal kidney function, and good tolerance, kidney ultrasound performed after 2months found nephrocalcinosis, without normalization of urinary oxalate (UOx). The dose was increased back to 6mg/kg, inducing a normalization in UOx. Nephrocalcinosis started to improve at month 10. Patient 2 was diagnosed at 2.5months (acute kidney failure); nephrocalcinosis was present from diagnosis. She received monthly lumasiran (6mg/kg), with progressive decrease in UOx and substantial improvement in kidney function but stable nephrocalcinosis after 9 injections. Patient 3 was diagnosed fortuitously (nephrocalcinosis) at 3.5months and received lumasiran before genetic diagnosis, leading to decreased UOx and maintenance of normal kidney function. Nephrocalcinosis improved after 5 injections.

    This report presents the youngest children treated with lumasiran worldwide. Lumasiran seems effective without side effects in infants but does not completely prevent the onset of nephrocalcinosis in the most severe forms. Higher doses than those proposed in the PIT might be required because of hepatic immaturity.

    This report presents the youngest children treated with lumasiran worldwide. Lumasiran seems effective without side effects in infants but does not completely prevent the onset of nephrocalcinosis in the most severe forms. Higher doses than those proposed in the PIT might be required because of hepatic immaturity.

    Transfer of follow-up care after pediatric kidney transplantation (KTx) may jeopardize quality of care and patient outcomes. We sought to determine if minority status and socioeconomic factors were associated with increased likelihood of follow-up outside a transplant center, and whether this transition of care was associated with worse long-term graft and patient survival.

    We performed an analysis of the United Network for Organ Sharing database, including children age < 18years who received a kidney transplant between 2003 and 2018. Survival analysis (conditional on survival with functioning graft to 1year) was performed using a Cox proportional hazards model where transfer of care (place of follow-up recorded as any setting other than a transplant center) was entered as a time-varying covariate.

    The study included 10,293, of whom 2083 received care outside of a transplant center during follow-up. Medicare coverage, but not minority race/ethnicity or socioeconomic status, was associated with increaor survival rates among minority populations. A higher resolution version of the Graphical abstract is available as Supplementary information.

    Cases of Henoch-Schönlein purpura nephritis (HSPN) with moderate severity were demonstrated to achieve good prognosis after treatment with renin-angiotensin system (RAS) inhibitors. However, some patients required additional treatment for recurrence after remission. This study aimed to clarify the effect of RAS inhibitors in HSPN cases with moderate severity, including the proportion of cases with recurrence and their response to additional treatment.

    Among 126 patients diagnosed with HSPN between 1996 and 2019, 71 patients with clinicopathologically diagnosed HSPN of moderate severity, defined as ISKDC grade II-IIIa and serum albumin ≥ 2.5 g/dL, were investigated.

    Proteinuria became negative after RAS inhibitor treatment alone in all 71 cases. However, 16 (22.5%) had recurrence. mTOR activation Eleven recurrent cases achieved negative proteinuria again following additional treatment. At the last follow-up (median 46.5 months; IQR, 23.2-98.2), 5 patients had persistent mild proteinuria; no patients had estimated glomeris available as Supplementary information.

    Despite the increase in experience and understanding of robotic thyroidectomy, its application for Graves‘ disease (GD) remains controversial. This study aimed to assess the safety and feasibility of robotic transaxillary thyroidectomy (RTT) for GD in comparison with the conventional open thyroidectomy (open group OG) approach.

    A total of 192 patients who underwent surgical resection for GD were retrospectively reviewed. mTOR activation Among them, 51 patients underwent RTT and the remaining 141 patients were in the conventional OG.

    All robotic operations were performed successfully without open conversion. Patients who underwent RTT were significantly younger (P < 0.001) and predominantly of the female sex. link=mTOR activation Operative time was longer for RTT than for the OG (182.5 ± 58.1 vs. 112.0 ± 29.5; P < 0.001). The mean intraoperative blood loss was not statistically different between RTT and the OG (113.3 ± 161.6 vs. 95.3 ± 209.1, P = 0.223). The mean weight of the resected thyroid was reduced in those who underwent RTT compared with open thyroidectomy (P = 0.033). The overall complication rate for RTT and open thyroidectomy was not significantly different (33.3% vs. 22.7%, P = 0.135). In RTT, the most common complication was transient hypocalcemia (21%). Permanent hypocalcemia and recurrent laryngeal nerve injury occurred in only one patient in each group. The weight of the resected thyroid was not related to the incidence of complications in patients receiving RTT.

    Considering excellent cosmesis, findings of this study support the safety and feasibility of RTT. Nevertheless, it should be performed by expert surgeons with extensive robotic surgery experience.

    Considering excellent cosmesis, findings of this study support the safety and feasibility of RTT. Nevertheless, it should be performed by expert surgeons with extensive robotic surgery experience.Biopolishing is a textile process that uses cellulases to improve the pilling resistance of fabrics. Although the process improves the pilling resistance, softness and color brightness of fabrics, it causes a significant loss of tensile strength in treated fabrics. The present work studied the use of cellulase immobilized on kaolin by adsorption and covalent bonding in biopolishing to get around this problem. The cellulase immobilization has been reported as promising alternative to overcome the inconvenient of biopolishing, but it has been very poorly explored. The results showed that cellulase immobilized by both covalent bonding and adsorption methods provided to the knitted fabric similar or superior pilling resistance to free cellulase, but with greater tensile strength. Immobilization also allowed for efficient recovery and reuse of the enzyme. The present work is a relevant contribution to the literature, since, as far as we know, it is the first work that shows it is possible to minimize the loss of tensile strength and also reuse the immobilized enzyme, giving a better-quality product and also contribution to reducing the cost of the polishing step.In many species, centromere identity is specified epigenetically by special nucleosomes containing a centromere-specific histone H3 variant, designated as CENP-A in humans and CID in Drosophila melanogaster. After partitioning of centromere-specific nucleosomes onto newly replicated sister centromeres, loading of additional CENP-A/CID into centromeric chromatin is required for centromere maintenance in proliferating cells. Analyses with cultured cells have indicated that transcription of centromeric DNA by RNA polymerase II is required for deposition of new CID into centromere chromatin. However, a dependence of centromeric CID loading on transcription is difficult to reconcile with the notion that the initial embryonic stages appear to proceed in the absence of transcription in Drosophila, as also in many other animal species. To address the role of RNA polymerase II-mediated transcription for CID loading in early Drosophila embryos, we have quantified the effects of alpha-amanitin and triptolide on centromeric CID-EGFP levels. Our analyses demonstrate that microinjection of these two potent inhibitors of RNA polymerase II-mediated transcription has at most a marginal effect on centromeric CID deposition during progression through the early embryonic cleavage cycles. Thus, we conclude that at least during early Drosophila embryogenesis, incorporation of CID into centromeres does not depend on RNA polymerase II-mediated transcription.To report the radiological features of intestinal ascariasis and to review the clinical implications of this re-emerging disease for adult population of the USA. This retrospective observational study involved 12 adult patients, whose radiological examinations disclosed unsuspected presence of ascaris in their intestinal tract. They were evaluated by computed tomography of the abdomen with oral contrast, small bowel series with barium, and magnetic resonance enterography. This series included 7 men and 5 women, who ranged in age from 19 to 72 years (mean age 48 years). The typical configuration of ascaris within the bowel loops was demonstrated on CT of the abdomen in 5 patients, small bowel examination with barium in 3, and by MR enterography in another 4 cases. Our study highlights the radiological appearances of intestinal ascariasis and the clinical implications of this resurging disease. The practicing radiologists should be aware of these findings, particularly when examining patients who have immigrated from or traveled to the endemic regions.

    Benzalkonium chloride (BAK), the most commonly used preservative in anti-glaucoma eye drops, inflicts damage to the ocular surface. A novel anti-glaucoma formulation that avoids the use of BAK has been developed. The aim of this study was to evaluate the cytotoxicity of this formulation and to compare it with an ophthalmic solution containing BAK.

    Two different latanoprost eye drops were used one ophthalmic solution (LSc) containing BAK 0.02% and one ophthalmic nanoemulsion (LNe) with a soft preservative (potassium sorbate 0.18%). Human epithelial conjunctival cells were incubated for 15, 30, and 60min with either LSc or LNe. The cytotoxicity was determined by MTT assay. Cell death was measured by flow cytometry using annexin V-FITC and propidium iodide.

    The values of cell viability and proliferation obtained from cells exposed to LNe were between 80 and 90% relative to the control group, whereas values obtained from cells exposed to LSc were around 30% at all study times (p < 0.05 at 15 and 30min; p < 0.01 at 60min). The percentage of viable cells decreased significantly when cells were incubated with LSc compared with cells incubated with LNe at all the study times, while the percentage of cells in late apoptosis/necrosis increased significantly in cells exposed to LSc compared to LNe.

    The new latanoprost nanoemulsion is significantly less cytotoxic on human conjunctival cells than LSc. These results suggest that the new formulation might be gentler on the eye surface than currently available BAK-preserved latanoprost solutions.

    The new latanoprost nanoemulsion is significantly less cytotoxic on human conjunctival cells than LSc. These results suggest that the new formulation might be gentler on the eye surface than currently available BAK-preserved latanoprost solutions.

    To review the role of curcumin in retinal diseases, COVID era, modification of the molecule to improve bioavailability and its future scope.

    PubMed and MEDLINE searches were pertaining to curcumin, properties of curcumin, curcumin in retinal diseases, curcumin in diabetic retinopathy, curcumin in age-related macular degeneration, curcumin in retinal and choroidal diseases, curcumin in retinitis pigmentosa, curcumin in retinal ischemia reperfusion injury, curcumin in proliferative vitreoretinopathy and curcumin in current COVID era.

    In experimental models, curcumin showed its pleiotropic effects in retinal diseases like diabetic retinopathy by increasing anti-oxidant enzymes, upregulating HO-1, nrf2 and reducing or inhibiting inflammatory mediators, growth factors and by inhibiting proliferation and migration of retinal endothelial cells in a dose-dependent manner in HRPC, HREC and ARPE-19 cells. In age-related macular degeneration, curcumin acts by reducing ROS and inhibiting apoptosis inducing proteinslarge randomized controlled trials are required to study its effects not only in treating retinal diseases in humans but in their prevention too.

    Individuals with a family history of type 2 diabetes (FH +) have an increased risk of developing type 2 diabetes. Circulating microRNAs (miRNAs) have been implicated as biomarkers of type 2 diabetes risk. Here, we investigated if four circulating miRNAs related to glucose metabolism were altered in men with a FH + and we conducted a preliminary analysis to determine if miRNA expressions were responsive to 8 weeks of combined exercise training.

    Sixteen young healthy men (mean ± SD; age 22.5 ± 2.5; BMI 26.4 ± 4.0) with FH + or without a family history of type 2 diabetes (FH -) underweight 8 weeks of combined endurance and resistance exercise training (n = 8 FH -; n = 8 FH +). The expression of miR-29a, miR-133a, miR-133b, and miR-155 were measured in serum before and after exercise training. QIAGEN’s Ingenuity

    Pathway Analysis was used to examine miRNA target genes and their involvement in glucose metabolism signaling pathways.

    There were no differences in miRNA expressions between FH - and FH + . Exercise training did not alter miRNA expressions in either FH - or FH + despite improvements in insulin sensitivity, aerobic capacity, and muscular strength. miR-29a and miR-155 were inversely related to fasting glucose, and miR-133a and miR-133b were negatively correlated with glucose tolerance; however, correlations were not observed with insulin sensitivity.

    The circulating miRNAs- miR-29a, miR-133a, miR-133b, and miR-155 are related to measures of glucose metabolism in healthy, normoglycemic men, but do not reflect peripheral insulin sensitivity or improvements in metabolic health following 8 weeks of combined exercise training.

    The circulating miRNAs- miR-29a, miR-133a, miR-133b, and miR-155 are related to measures of glucose metabolism in healthy, normoglycemic men, but do not reflect peripheral insulin sensitivity or improvements in metabolic health following 8 weeks of combined exercise training.Switching between competing tasks is supported by active inhibition of the preceding task. The level of task stimulus processing at which interference between competing tasks must occur for inhibition to be recruited is still unclear. Here, we investigated whether inhibition is recruited by task conflict occurring at an early or late (semantic) stage of task stimulus processing by dissociating the task stimulus format from its meaning. In two experiments, participants performed three different numerical judgment tasks on numerical stimuli that could be presented as digits or number words (e.g., „6“ or „six“) in a cued task-switching procedure. The effects of the change of stimulus format for the inhibition of the previous task were investigated and assessed by the N-2 task repetition cost, an index of the extent to which task representations are inhibited. The N-2 task repetition cost observed in the same stimulus format condition disappeared when target stimuli on task N-1 were presented in a different format from stimuli of task N-2 and N. This occurred both when the format changed from digits to number words stimuli (Experiment 1) as well as when it changed from number words to digits stimuli (Experiment 2). Results indicated that task set inhibition is recruited very early during the stimulus processing stage. They also provided evidence that task inhibition is not tied to task preparation processes but operates as a reactive, rather than proactive mechanism of conflict resolution.

    Gram-negative bacteria occur commonly in the inner tissues of stored coniferous and deciduous timber, showing a marked variation in numbers. The greatest maximal numbers are found in the sapwood of coniferous timber. The common constituents of the Gram-negative biota are potentially pathogenic species of Enterobacteriaceae family of the genera Rahnella, Pantoea, Enterobacter, and Klebsiella. The air of wood-processing facilities is polluted with the wood-borne Gram-negative bacteria and produced by them endotoxin, as demonstrated worldwide by numerous studies.

    There are three potential pathways of the pathogenic impact of wood-borne Gram-negative bacteria on exposed woodworkers allergic, immunotoxic, and infectious. Allergic impact has been underestimated for a long time with relation to Gram-negative bacteria. Hopefully, the recent demonstration of the first documented case of hypersensitivity pneumonitis (HP) in woodworkers caused by Pantoea agglomerans which developed in extremely large quantities in bbeen confirmed.

    Summarizing, Gram-negative bacteria-inhabiting timber should be considered, besides filamentous fungi and actinobacteria, as important risk factors of occupational disease in woodworkers that could be either HP with allergenic background or toxic pneumonitis elicited by endotoxin.

    Summarizing, Gram-negative bacteria-inhabiting timber should be considered, besides filamentous fungi and actinobacteria, as important risk factors of occupational disease in woodworkers that could be either HP with allergenic background or toxic pneumonitis elicited by endotoxin.The first experimental vaccinations against hepatitis B virus (HBV) were performed in 1970, even before the nature of the administered „Australia antigen“ was known. Soon, it was realized that this antigen was the envelope protein (HBV surface antigen, HBsAg), and it was purified from HBV-containing human plasma. Later, it was produced in genetically engineered yeast cells. The excellent efficacy of the HBsAg vaccine was confirmed in numerous studies, particularly in newborns from HBV-infected mothers who almost always become chronic HBV carriers without vaccination. But the vaccine is also highly effective in older children and adults and has been applied worldwide since 1984, leading to a circa tenfold decrease of HBV infections in the vaccinated.Still, there are several challenges with hepatitis B vaccination. In newborns from mothers with very high virus load, the vaccine may fail. Recipients who are immunocompromised, older, smokers, or obese may not produce protective antibodies. Early studies suggested that the vaccine with HBsAg subtype adw2 also protected against infections by other subtypes, but recent observations show that the protection is weaker against heterologous subtypes. Occasionally, escape mutations may develop.Most current HB vaccines are based on the knowledge of 40 years ago and could be significantly improved. Inclusion of the currently neglected preS domains in the HBV envelope would add the most important protective T‑ and B‑cell epitopes to the vaccines. Expression of the HBsAg in mammalian cell cultures would enhance the folding of neutralizing HBsAg epitopes. Use of the regionally prevalent HBsAg subtypes would increase the protection. Optimal adjuvants and epitope carriers may enhance the immunogenicity to the level necessary for immune therapy of chronic hepatitis B.Worldwide, the hepatitis B and hepatitis C viruses (HBV, HCV) are the most relevant causative viral agents of a chronic hepatitis (inflammation of the liver). At present, more than 250 million people suffer from a chronic HBV infection globally, resulting in 0.8 million deaths per year. A chronic HCV infection accounts for about 70 million cases worldwide, leading to a death toll of about 1 million per year. An approved vaccine is only available against an HBV infection. Both HBV and HCV infections result in a highly increased risk of developing liver fibrosis, cirrhosis, and a hepatocellular carcinoma (HCC).This review aims to describe mechanisms of the HBV- and HCV-associated pathogenesis. link2 The focus is on the interplay between a chronic infection with intracellular signaling transduction, metabolic pathways with an emphasis on lipid metabolism, the establishment of liver fibrosis and cirrhosis during a chronic infection, and the mechanisms of the onset of a virally induced HCC.Despite there being great advances in the characterization of viral life cycles and the development of robust antiviral strategies, significant hurdles persist gaining a better understanding of the mechanisms that drive virus-associated pathogenesis as well as increasing insights regarding different viral genotypes having impacts on alternate pathogeneses.The National Reference Center (NRC) for hepatitis B viruses (HBV) and hepatitis D viruses (HDV) has been located at the Institute of Medical Virology of the Justus Liebig University (JLU) in Giessen, Germany, since its establishment in 2011. This paper describes the NRC’s areas of activity and related experience.The NRC offers comprehensive consulting services on all diagnostic and clinical aspects of acute and chronic HBV and HDV infections for the Public Health Service (ÖGD), diagnostic laboratories, clinics, research institutes, and physicians in private practice. Uncertain diagnostic findings can be analyzed and interpreted and epidemiological correlations clarified with the HBV/HDV special diagnostics established at the NRC using state-of-the-art molecular, biochemical, and genetic laboratory tools. The NRC has access to a strain collection of many well-characterized and cloned HBV/HDV isolates, allowing comparative analysis and evaluation of antiviral resistance mutations and immune escape variants. Together with its national and international partner institutions, the NRC initiates and supervises, among other things, interlaboratory studies for the diagnosis of HBV resistance and immune escape for the establishment and validation of international World Health Organization (WHO) standards and for the improvement of quantitative HDV genome determination. The NRC actively participates in current recommendations and guidelines on HBV and HDV and the recommendations of medical societies. It also highlights current HBV/HDV-relevant aspects with contributions in the form of national and international lectures as well as original articles and comments in national and international journals.The incidence of hepatitis C virus (HCV) infections remains high even more than 10 years after approval of the first direct-acting antivirals for treatment of hepatitis C. In some countries, more people are newly infected with the virus than patients cured by antiviral therapy. The development of a prophylactic vaccine could prevent virus transmission and thereby make a significant contribution to control the global burden of this disease. In this article, we review the unique challenges and current approaches to HCV vaccine development.HCV is a highly diverse and versatile virus that mostly escapes the immune system and establishes chronic infections. However, up to one third of the exposed individuals can spontaneously resolve HCV infections, which indicates that protective immunity can be achieved. Numerous studies on determinants of protective immunity against HCV show an increasingly complete picture of what a vaccine must achieve. It is very likely that both strong neutralizing antibodies and powerful cytotoxic T cells are needed to reliably protect against chronic HCV infection. The key question is which approaches allow maturation of particularly broadly effective antibodies and T cells. This will be necessary to protect against the high number of different HCV variants. The recent successes of mRNA vaccines open new doors for HCV vaccine research and development. Combined with a deeper understanding of the structure and function of the viral envelope proteins, the identification of cross-protective antibody and T‑cell epitopes as well as the use of standardized methods to quantify the effectiveness of vaccine candidates, new perspectives arise for the development of a vaccine.

    Compliance is the ability of a hollow organ to dilate and increase volume withan increase in pressure, an accurate representation of food bolus transit through the gastroesophageal junction (GEJ). Impedance planimetry system can calculate compliance (change in volume over pressure) and distensibility (cross-sectional area over pressure) of the GEJ. We aim to describe the changes in compliance during anti-reflux surgery and hypothesize that compliance is a better predictor of patient outcomes than distensibility (DI).

    A review of a prospectively maintained quality database was performed. Patients with FLIP measurements during laparoscopic fundoplication between August 2018 and June 2021 were included. GEJ compliance and DI were measured after hernia reduction, cruroplasty, and fundoplication. Patient-reported outcomes were collected through standardized surveys up to 2years after surgery. A scatter plot was used to identify a correlation between compliance and DI. Comparisons of measurements between time p 79 mm

    /mmHg may prevent postoperative dysphagia. Therefore, GEJ compliance is an underutilized FLIP measurement warranting further investigation.

    Compliance and DI are strongly associated displaying the same directional change during anti-reflux surgery. GEJ compliance of 80-92 mm3/mmHg revealed the best patient-reported outcome scores, and avoiding a compliance ≤ 79 mm3/mmHg may prevent postoperative dysphagia. Therefore, GEJ compliance is an underutilized FLIP measurement warranting further investigation.A soft and flexible wearable sweat epidermal microfluidic device capable of simultaneously stimulating, collecting, and electrochemically analyzing sweat is demonstrated. The device represents the first system integrating an iontophoretic pilocarpine delivery system around the inlet channels of epidermal polydimethylsiloxane (PDMS) microfluidic device for sweat collection and analysis. The freshly generated sweat is naturally pumped into the fluidic inlet without the need of exercising. Soft skin-mounted systems, incorporating non-invasive, on-demand sweat sampling/analysis interfaces for tracking target biomarkers, are in urgent need. link2 Existing skin conformal microfluidic-based sensors for continuous monitoring of target sweat biomarkers rely on assays during intense physical exercising. link3 This work demonstrates the first example of combining sweat stimulation, through transdermal pilocarpine delivery, with sample collection through a microfluidic channel for real-time electrochemical monitoring of sweat glucose, in a fully integrated soft and flexible multiplexed device which eliminates the need of exercising. The on-body operational performance and layout of the device were optimized considering the fluid dynamics and evaluated for detecting sweat glucose in several volunteers. Furthermore, the microfluidic monitoring device was integrated with a real-time wireless data transmission system using a flexible electronic board PCB conformal with the body. The new microfluidic platform paves the way to real-time non-invasive monitoring of biomarkers in stimulated sweat samples for diverse healthcare and wellness applications.Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening inflammatory syndrome that can be triggered by autoimmune diseases, malignancy, or infection. In rheumatologic patients, sHLH is referred to as macrophage activation syndrome (MAS). Differentiating between triggers is important for prompt treatment and prognosis. Data comparing subsets of sHLH are limited due to the rarity of this disease. We aim to explore differences in clinical features that may differentiate MAS from malignancy-associated HLH (mHLH) patients. We conducted a single-center retrospective study assessing clinical characteristics, laboratory parameters, treatment regimens and outcomes in 34 patients with sHLH over a 16 year period. We compared patients with MAS to those with mHLH. Hepatomegaly was not present in the MAS group but was present in the mHLH group (0 vs. 25%, p = 0.024). MAS patients had on average nearly double the concentration of platelets at 50.0 (IQR 31.0-78.0 Kµ/L) vs. 29.0 Kµ/L (IQR 14.0-37.5 Kµ/L), p = 0.003. Soluble IL-2R concentrations were four times lower in the MAS group with a median soluble IL-2R concentration of 6814.5 kU/L (IQR 2101-2610 kU/L) vs. 27972.0 kU/L (IQR 12,820-151,650 kU/L), p = 0.010. The MAS group fared better overall than the mHLH group but was not statistically significant (mortality 22 vs. 44%, p = 0.18). MAS and mHLH patients exhibited different laboratory parameters and clinical features, most notably differences in platelet counts, soluble IL-2R concentration and hepatomegaly, which may help differentiate these conditions early in their course.To investigate the effect of a structured exercise training program on pain, functional status, physical function and quality of life (QoL) in string and woodwind players with nonspecific cervical pain. This study had a prospective cohort design and conducted on 40 musicians (26 male, 14 female) aged between 18 and 65 years with persistent nonspecific neck pain in the previous 3 months. Forty musicians were assigned to either violin (n = 20, median age; 26.5 year, height; 1.67 m, body mass; 65 kg, BMI; 23.04 kg/m2) or ney group (n = 20, median age; 27.5 year, height; 1.81 m, body mass; 75 kg, BMI; 23.35 kg/m2) and followed the same structured exercise program (3 days/per week for 8 weeks). The primary outcome was neck pain intensity and assessed on a visual analog scale (VAS). Secondary outcomes; cervical range of motion (ROM) was measured using a goniometer, the jaw-to-sternum and jaw-to-wall distances were used for the assessment of cervical mobility, neck, shoulder and back muscles strength were assessed wuscle groups recovered differently. Physical needs specific to the instrument and performance should be taken into account when prescribing exercises to musicians having the same problem, but playing different instruments.

    Resection arthroplasty of the trapezium with or without tendon interposition is the standard procedure in the treatment of advanced, symptomatic thumb carpometacarpal joint osteoarthritis. Treatment recommendation in the early stages without visible or minimal radiographic changes is often difficult, especially when conservative treatment methods have already been exhausted. In these cases, there is the possibility of the minimally invasive methods of denervation, arthroscopic procedures and autologous fat transplantation.

    Which minimally invasive procedures are available for the treatment of thumb carpometacarpal joint osteoarthritis and how is their value to be assessed?

    The minimally invasive methods of denervation, arthroscopic procedures and autologous fat transplantation for the treatment of thumb carpometacarpal joint osteoarthritis are described and current results from the literature are discussed.

    Good results have been reported with all three procedures. However, the reports are almost exclusively based on retrospective studies with small numbers of patients, which lack control groups, so the results cannot be regarded as definitive.

    Denervation, arthroscopic procedures and autologous fat transplantation appear to be suitable methods in the early stages of thumb carpometacarpal joint osteoarthritis. Further studies, especially comparative randomised trials that report medium and long-term results, would allow further assessment of these methods.

    Denervation, arthroscopic procedures and autologous fat transplantation appear to be suitable methods in the early stages of thumb carpometacarpal joint osteoarthritis. Further studies, especially comparative randomised trials that report medium and long-term results, would allow further assessment of these methods.

    The hearing outcome of idiopathic sudden sensorineural hearing loss (ISSNHL) is hard to predict. We herein constructed a multiple regression model for hearing outcomes in each frequency separately in an attempt to achieve practical prediction in ISSNHL.

    We enrolled 235 consecutive in-patients with ISSNHL who were treated in our department from 2015 to 2020 (average hearing level at 250-4000Hz ≥ 40dB; time from onset to treatment ≤ 14days; 126 males/109 females; age range 17-87years (average 61.0years)). All patients received systemic prednisolone administration combined with intratympanic dexamethasone injection. The pure-tone hearing threshold of 125-8000Hz was measured at every octave before (HL

    ) and after (HL

    ) treatment. A multiple regression model was constructed for HL

    (dependent variable) using five explanatory variables (age, days from onset to treatment, presence of vertigo, HL

    , and hearing level of the contralateral ear).

    The multiple correlation coefficient increased as the frequency increased. Strong correlations were seen in high frequencies, with multiple correlation coefficients of 0.784/0.830 for 4000/8000Hz. The width of the 70% prediction interval was narrower for 4000/8000Hz (± 18.2/16.3dB) than for low to mid-frequencies. Among the five explanatory variables, HL

    showed the largest partial correlation coefficient for any frequency. The partial correlation coefficient for HL

    increased as the frequency increased, which may partially explain the high multiple correlation coefficients for high frequencies.

    The present model would be of practical use for predicting hearing outcomes in high frequencies in patients with ISSNHL.

    The present model would be of practical use for predicting hearing outcomes in high frequencies in patients with ISSNHL.

    This study aimed to estimate the incidence of fecal incontinence (FI) and identify risk factors in a cohort of older individuals.

    In 2006, individuals aged ≥ 60years were selected from the SABE study. The dependent variable was FI in 2010. FI was assessed using the question „In the last 12 months, have you ever lost control of bowel movements or stools?“ Incidence was measured in units of per 1000 person-years. Multivariate analysis was used to assess risk factors for FI.

    This study was the first to examine the incidence of FI in older Brazilian individuals. In total, 1413 individuals were included; mean age was 74.5years, and 864 (61.8%) participants were women. FI prevalence rates were 4.7% for men and 7.3% for women. Incidence rate of FI was 16.3 and 22.2 per 1000 person-years for men and women, respectively. The risk of FI was greater among women aged ≥ 75years, with severe symptoms of depression, cancer (other than skin) and chronic obstructive pulmonary disease (COPD). In men, the risk of FI was greater among those with poor literacy (up to 3years of schooling), an Instrumental Activities of Daily Living (IADL) category of 1-4 and those who self-reported „bad/very bad“ health status.

    The FI incidence rate was high. The identified risk factors were age ≥ 75years, with severe symptoms of depression, cancer and COPD (women); having up to 8years of schooling; IADL category of 1-4 and self-reported health status (men).

    The FI incidence rate was high. The identified risk factors were age ≥ 75 years, with severe symptoms of depression, cancer and COPD (women); having up to 8 years of schooling; IADL category of 1-4 and self-reported health status (men).

    The aims of this study were to evaluate the effects of systemic administration of Salvia officinalisLinnaeus(L.) leaf extract on new bone formation in the expanded premaxillary suture in rats in vivo and to examine the antioxidant effects and phenolic profile of Salvia officinalis (SO) leaf and root extracts in vitro.

    Fourteen male Sprague Dawley rats were allocated to two groups SO group (n = 7) and control group (n = 7). An open-loop spring was attached to the upper incisors of each rat to expand the premaxillae. A5-day expansion period followed by a12-day retention period was observed. The rats in the SO group received systemic administration of 20 mg SO/kg/day via the orogastric route for 17days. Histomorphometric examinations were carried out to examine the amount of new bone formation, number of capillaries, and intensity of inflammatory cell response. Immunohistochemical analysis was conducted to examine the number of osteoblasts and osteoclasts. Leaf and root extracts of SO were also analyzed for antioxidant activity and phenolic compounds in vitro.

    Statistical analysis showed that the following were higher in the SO group than in the control group new bone formation, number of osteoblasts and osteoclasts, intensity of inflammatory cell response (neutrophils, lymphocytes, and macrophages), and number of capillaries. The major compound identified in SO leaf extract was rosmarinic acid, while luteolin derivatives, salvianolic acidF, and medioresinol were also present.

    Salvia officinalisL. from leaf extract provided antioxidant effects and stimulated enhanced new bone formation in the expanded midpalatal suture after maxillary expansion in rats.

    Salvia officinalis L. from leaf extract provided antioxidant effects and stimulated enhanced new bone formation in the expanded midpalatal suture after maxillary expansion in rats.Cardiogenic shock as a complication of myocardial infarction (5-10%) increases the mortality of uncomplicated myocardial infarction from less than 10% to 40%. This is due to the development of multiple organ dysfunction syndrome triggered by the extensive shock-induced impairment of organ perfusion. Therefore, guideline-based treatment should not only be restricted to reopening of the occluded coronary artery and management of complications of the infarction important for survival are also guideline-driven optimization of organ perfusion by inotropic and vasoactive substances and, with well-defined indications, by temporary mechanical circulatory support but not by intra-aortic counterpulsation. Equally important, however, are shock-specific intensive care measures to prevent or attenuate organ dysfunction, such as lung protective ventilation in cases where ventilation is obligatory.The authors utilised the Irish Hip Fracture Database (IHFD) to quantify the impact of hip fracture on the health service in terms of incidence, bed days and financial costs. The absolute number of hip fracture cases recorded by the IHFD has increased, as has the associated costs of hospitalisation.

    Hip fracture places a considerable clinical and financial burden on the healthcare system, with acute hospitalisation accounting for a substantial proportion of the costs incurred. link3 This paper aimed to quantify the cost of hospitalisation for hip fracture in Ireland in terms of bed days and direct hospital costs.

    The authors analysed 23,494 cases in the Irish Hip Fracture Database (IHFD) from 2014 to 2020. Case numbers and length of stay were analysed annually. Hospital costs for hip fracture were described using the 2020 Activity-Based Funding Price List, which outlines the fees paid to public hospitals for inpatient activity.

    For the time period 2014-2020, the total cost of hospitalisation for hip fracture waand maximise the use of community services and early supportive discharge for the rehabilitation phase.

    Firefighters are exposed to a variety of known and suspected carcinogens through their work. However, the association with cancer risk has limited evidence. We examined cancer incidence among firefighters in the newly established Norwegian Fire Departments Cohort restricted to sites with established associations with carcinogens encountered during firefighting. This included sites within the respiratory, urinary, and lympho-hematopoietic systems, and the skin and all sites combined.

    Male firefighters (N=3881) in the cohort were linked to the Cancer Registry of Norway for incident cancer cases occurring during the period 1960-2018. We calculated standardized incidence ratios (SIR) with rates for the national male population as reference, and stratified SIR analyses by period of first employment, duration of employment, and time since first employment.

    Elevated risk was seen for all sites combined (SIR 1.15, 95% confidence interval 1.07-1.23). Elevated risk of urinary tract cancer was observed among firefprotective equipment.Galectin-8 (Gal-8) belongs to a family of animal lectins that modulate cell adhesion, cell proliferation, apoptosis, and immune responses. Recent studies have shown that mammalian Gal-8 induces in an autocrine and paracrine manner, the expression and secretion of cytokines and chemokines such as RANKL, IL-6, IL-1β, SDF-1, and MCP-1. This involves Gal-8 binding to receptor complexes that include MRC2/uPAR/LRP1, integrins, and CD44. Receptors ligation triggers FAK, ERK, Akt, and the JNK signaling pathways, leading to induction of NF-κB that promotes cytokine expression. Indeed, immune-competent Gal-8 knockout (KO) mice express systemic lower levels of cytokines and chemokines while the opposite is true for Gal-8 transgenic animals. Cytokine and chemokine secretion, induced by Gal-8, promotes the migration of cancer cells toward cells expressing this lectin. Accordingly, Gal-8 KO mice experience reduced tumor size and smaller and fewer metastatic lesions when injected with cancer cells. These observations suggest the existence of a ‚vicious cycle‘ whereby Gal-8 expression and secretion promotes the secretion of cytokines and chemokines that further promote Gal-8 expression. This ‚vicious cycle‘ could enhance the development of a ‚cytokine storm‘ which is a key contributor to the poor prognosis of COVID-19 patients.

    We tested whether the concurrence of food intake and elevated concentrations of endogenous melatonin, as occurs with late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin receptor-1B gene (MTNR1B).

    In a Spanish natural late-eating population, a randomized, crossover study was performed. Each participant (n = 845) underwent two evening 2-h 75-g oral glucose tolerance tests following an 8-h fast an early condition scheduled 4 h prior to habitual bedtime („early dinner timing“) and a late condition scheduled 1 h prior to habitual bedtime („late dinner timing“), simulating an early and a late dinner timing, respectively. Differences in postprandial glucose and insulin responses between early and late dinner timing were determined using incremental area under the curve (AUC) calculated by the trapezoidal method.

    Melatonin serum levels were 3.5-fold higher in the late versus early condition, with late dinner timing resulting in 6.

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