Uveitis Associated with Monogenic Autoinflammatory Syndromes in Children.

Monogenic autoinflammatory syndromes (MAISs), are caused by pathogenic genetic variants in the innate immune system, leading to dysregulation and aberrant inflammasome activation spontaneously or with minimal triggering. The diagnosis and treatment of MAISs can be intricate, relying on an increased recognition of potential differential diagnoses. This review examines the clinical features of MAIS, with a special focus on uveitis. It also evaluates treatment options and assesses the effects of activating molecular and cytokine pathways.

Prevalence and barriers of reporting needle-stick injures amongst government pharmacists working in Perak, Malaysia.

INTRODUCTION: Needle-stick injuries (NSIs) are common amongst healthcare workers including pharmacists. Studies have reported a range of 0-5.65 per 1,000 pharmacists handling vaccinations that suffered at least one incident of NSI. The objective of this study was to determine the prevalence of NSI and the barriers encountered in reporting it amongst government pharmacists working in Perak. MATERIALS AND METHODS: This was a cross-sectional study conducted amongst all government pharmacists in Perak. We excluded those who did not consent or were unreachable electronically. The researchers provided an online link that was forwarded to all heads of departments in Perak via social media. The respondents answered their demographic details, questions assessing their knowledge of NSI transmissible diseases, needle-stick handling practices, detail experiences of them suffering an NSI (all self-developed questionnaires), and their barriers in reporting an NSI (validated questionnaire). All responses were auto-tabulated in an excel sheet. A sample size of 516 pharmacists was needed for this study. A respondent was deemed to have inadequate knowledge when they answered any question wrongly about NSI knowledge-related questions and inappropriate practice in needle handling when respondents answered any questions wrongly for questions assessing practices. RESULTS: A total of 524 pharmacists participated. The overall prevalence of NSI was 23.1% (n=121), of which, those with contaminated NSI were 10.3% (n=54, 95%CI: 7.9-13.30). Twothirds of the participants (66.6%) had inadequate knowledge and nearly all of them were unable to describe the appropriate needle-handling practices (94.7%). Amongst the reported barriers were "not knowing whose duty it was to report an NSI" (45.5%) and "busy schedules" (44.7%). CONCLUSION: One in every five pharmacists in the state of Perak had a history of NSI, and 1 in every 10 had sustained a contaminated NSI. The barriers to reporting a NSI were mainly due to uncertainty about whose responsibility to report the incident and being too busy to report it.

In silico structural modeling and quality assessment of Plasmodium knowlesi apical membrane antigen 1 using comparative protein models.

Plasmodium knowlesi is the most common zoonotic parasite associated with human malaria infection in Malaysia. Apical membrane antigen 1 (AMA1) protein in the parasite plays a critical role in parasite invasion into host cells. To date, there is no complete three-dimensional ectodomain structure of P. knowlesi AMA1 (PkAMA1) protein. The knowledge of a protein structure is important to understand the protein molecular functions. Three in silico servers with respective structure prediction methods were used in this study, i.e., SWISS-MODEL for homology modeling and Phyre2 for protein threading, which are template-based modeling, while I-TASSER for template-free ab initio modeling. Two query sequences were used in the study, i.e., native ectodomain of PkAMA1 strain H protein designated as PkAMA1-H and a modified PkAMA1 (mPkAMA1) protein sequence in adaptation for Pichia pastoris expression. The quality of each model was assessed by ProSA-web, QMEAN and SAVES v6.0 (ERRAT, Verify3D and Ramachandran plot) servers. Generated models were then superimposed with two models of Plasmodium AMA1 deposited in Protein Data Bank (PDB), i.e., PkAMA1 (4UV6.B) and Plasmodium vivax AMA1 (PvAMA1, 1W81) protein structures for similarity assessment, quantified by root-meansquare deviation (RMSD) value. SWISS-MODEL, Phyre2 and I-TASSER server generated two, one and five models, respectively. All models are of good quality according to ProSA-web assessment. Based on the average values of model quality assessment and superimposition, the models that recorded highest values for most parameters were selected as best predicted models, i.e., model 2 for both PkAMA1-H and mPkAMA1 from SWISS-MODEL as well as model 1 of PkAMA1-H and model 3 of mPkAMA1 from I-TASSER. Template-based method is useful if known template is available, but template-free method is more suitable if there is no known available template. Generated models can be used as guidance in further protein study that requires protein structural data, i.e., protein-protein interaction study.

Blends of palm kernel oil, soybean oil and palm stearin as an alternative to milk fat for frozen dessert application.

In this study, the ternary blends of palm kernel oil (PKO), soybean oil (SBO) and two types of palm stearin (PS) (PS33 and PS38) were systematically prepared and evaluated for their application as an alternative to milk fat in frozen dessert. The physicochemical characteristics namely fatty acids constituent, triacylglycerols (TAGs) composition, melting behavior, solid fat content (SFC) and microstructure were studied. All ternary blends of PKO/SBO/PS33 and PKO/SBO/PS38 had comparable microstructure to that of milk fat. However, 80/15/5 (PKO/SBO/PS33) and 80/15/5 to 80/5/15 (PKO/SBO/PS38) mixtures were found to have similar SFC as milk fat at temperature above 20 °C, allowing these ternary blends to be completely melted at body temperature. With this, 80/15/5 (PKO/SBO/PS33) and 80/15/5 to 80/5/15 (PKO/SBO/PS38) mixtures were able to provide similar meltdown and mouth feel as milk fat at room temperature. Nonetheless, fatty acids constituent, TAGs composition and melting behavior of the blends were different from milk fat. This study showed that ternary blends of PKO, SBO and PS at ratios 80/15/5 (PKO/SBO/PS33) and 80/15/5 to 80/5/15 (PKO/SBO/PS38) can be potentially used as a milk fat alternative for frozen dessert application based on its similar microstructure and SFC profile as the milk fat. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05507-z.

Subcutaneous and visceral adipose tissue in patients with primary and recurrent incisional hernia.

PURPOSE: Visceral obesity rather than body mass index has been reported to be associated with a higher incidence of incisional hernias. The aim of this study was to examine the relationship between CT measured adipose tissue and muscle in primary and recurrent incisional hernia. METHODS: Patients with a 'Primary' or 'Recurrent incisional hernia' were obtained from a prospective cohort of patients who were being assessed for incisional hernia repair over a 2-year period. Computerised tomography (CT)-images were analysed using NIH Image-J software to quantify adipose tissue and skeletal muscle cross-sectional areas at the level of lumber vertebra 3/4 using standard Hounsfield units. To test inter-observer 'absolute agreement', each parameter was measured independently by two investigators and reliability analysis performed. RESULTS: Thirty-six patients were included in the study: 15 had a Primary while 21 had a Recurrent incisional hernia. Both groups had similar baseline characteristics. Reliability analysis for CT-measured areas showed very high interclass correlation coefficient (ICC) between observers. Patients in the recurrent group had significantly greater subcutaneous adipose tissue (SAT) [median = 321.9cm2 vs 230.9cm2, p = 0.04] and visceral adipose tissue (VAT) [median = 221.1cm2 vs 146.8cm2, p = 0.03] than those in the primary group. There was no difference in skeletal muscle areas for right [median = 2.8cm2 vs 2.9cm2] and left [median = 3.7cm2 vs 4.1cm2] rectus muscles between groups. CONCLUSION: Our study shows that patients with a recurrent incisional hernia have significantly more subcutaneous and visceral adipose tissue than those with a primary incisional hernia. Further studies in this area are required if we are to reduce the burden of recurrent hernia following repair of a primary incisional hernia.

Long term outcome and elasticity of a polyester mesh used for laparoscopic ventral hernia repair.

BACKGROUND: Repair of a ventral hernia is increasingly being performed by a laparoscopic approach despite lack of good long term follow up data on outcomes. The aim of this study was to examine the long term performance of a polyester mesh and to assess its elastic properties in patients undergoing laparoscopic ventral hernia repair. METHODS: All patients being assessed for a ventral hernia repair between August 2011 and November 2013 were placed on a prospective database. Those undergoing laparoscopic repair with a polyester mesh were seen at clinic at one month and one year, while their electronic records were assessed at 34 months (range 24-48 months) and 104 months (range 92-116 months). In addition, CT scans of the abdomen and pelvis performed for any reason on these patients during the follow up period were reviewed by a consultant gastrointestinal radiologist. Mechanical failure testing of the mesh was also performed. RESULTS: Thirty-two of the 100 patients assessed for ventral hernia repair had a laparoscopic repair with a polyester mesh. Nineteen (59%) had CT scans performed during the follow-up period. No recurrence was recorded at 34 months, while three (9.4%) had a recurrence at 104 months. Two had central breakdown of the mesh at 81 and 90 months, while 1 presented acutely at 116 months after operation. Mesh had stretched across the defect by an average of 21% (range 5.7-40%) in nine patients. Mechanical testing showed that this mesh lost its elasticity at low forces ranging between 1.8 and 3.2 N/cm. CONCLUSION: This study shows that late recurrence is a problem following laparoscopic ventral hernia repair with polyester mesh. The mesh loses it elasticity at a low force. This combined with degradation of mesh seems the most likely cause of failure. This is unlikely to be a unique problem of polyester mesh and further long-term studies are required to better assess this operative approach to ventral hernia repair.

In silico structural modeling and quality assessment of Plasmodium knowlesi apical membrane antigen 1 using comparative protein models

@#Plasmodium knowlesi is the most common zoonotic parasite associated with human malaria infection in Malaysia. Apical membrane antigen 1 (AMA1) protein in the parasite plays a critical role in parasite invasion into host cells. To date, there is no complete three-dimensional ectodomain structure of P. knowlesi AMA1 (PkAMA1) protein. The knowledge of a protein structure is important to understand the protein molecular functions. Three in silico servers with respective structure prediction methods were used in this study, i.e., SWISS-MODEL for homology modeling and Phyre2 for protein threading, which are template-based modeling, while I-TASSER for template-free ab initio modeling. Two query sequences were used in the study, i.e., native ectodomain of PkAMA1 strain H protein designated as PkAMA1-H and a modified PkAMA1 (mPkAMA1) protein sequence in adaptation for Pichia pastoris expression. The quality of each model was assessed by ProSA-web, QMEAN and SAVES v6.0 (ERRAT, Verify3D and Ramachandran plot) servers. Generated models were then superimposed with two models of Plasmodium AMA1 deposited in Protein Data Bank (PDB), i.e., PkAMA1 (4UV6.B) and Plasmodium vivax AMA1 (PvAMA1, 1W81) protein structures for similarity assessment, quantified by root-meansquare deviation (RMSD) value. SWISS-MODEL, Phyre2 and I-TASSER server generated two, one and five models, respectively. All models are of good quality according to ProSA-web assessment. Based on the average values of model quality assessment and superimposition, the models that recorded highest values for most parameters were selected as best predicted models, i.e., model 2 for both PkAMA1-H and mPkAMA1 from SWISS-MODEL as well as model 1 of PkAMA1-H and model 3 of mPkAMA1 from I-TASSER. Template-based method is useful if known template is available, but template-free method is more suitable if there is no known available template. Generated models can be used as guidance in further protein study that requires protein structural data, i.e., protein-protein interaction study.

Bioinformatics characterization of Plasmodium knowlesi apical membrane antigen 1 (PkAMA1) for multi-epitope vaccine design.

Malaria caused by Plasmodium knowlesi species has become a public health concern, especially in Malaysia. Plasmodium knowlesi parasite which originates from the macaque species, infects human through the bite of the Anopheles mosquitoes. Research on malaria vaccine has been a continuous effort to eradicate the malaria infection, yet there is no vaccine against P. knowlesi malaria to date. Apical membrane antigen 1 (AMA1) is a unique surface protein of all apicomplexan parasites that plays a crucial role in parasite-host cell invasion and thus has been a long-standing malaria vaccine candidate. The selection of protective epitopes in silico has led to significant advances in the design of the vaccine. The present study aimed to employ bioinformatics tools to predict the potential immunogenic B- and T-cell epitopes in designing malaria vaccine targeting P. knowlesi AMA1 (PkAMA1). B-cell epitopes were predicted using four bioinformatics tools, i.e., BepiPred, ABCpred, BcePred, and IEDB servers whereas T-cell epitopes were predicted using two bioinformatics servers, i.e., NetMHCpan4.1 and NetMHCIIpan-4.0 targeting human major histocompatibility complex (MHC) class I and class II molecules, respectively. The antigenicity of the selected epitopes computed by both B- and T-cell predictors were further analyzed using the VaxiJen server. The results demonstrated that PkAMA1 protein encompasses multi antigenic regions that have the potential for the development of multi-epitope vaccine. Two B- and T-cell epitopes consensus regions, i.e., NSGIRIDLGEDAEVGNSKYRIPAGKCP (codons 28-54) and KTHAASFVIAEDQNTSY RHPAVYDEKNKT (codons 122-150) at domain I (DI) of PkAMA1 were reported. Advancement of bioinformatics in characterization of the target protein may facilitate vaccine development especially in vaccine design which is costly and cumbersome process. Thus, comprehensive B-cell and T-cell epitope prediction of PkAMA1 offers a promising pipeline for the development and design of multi-epitope vaccine against P. knowlesi.

Bioinformatics characterization of Plasmodium knowlesi apical membrane antigen 1 (PkAMA1) for multi-epitope vaccine design

@#Malaria caused by Plasmodium knowlesi species has become a public health concern, especially in Malaysia. Plasmodium knowlesi parasite which originates from the macaque species, infects human through the bite of the Anopheles mosquitoes. Research on malaria vaccine has been a continuous effort to eradicate the malaria infection, yet there is no vaccine against P. knowlesi malaria to date. Apical membrane antigen 1 (AMA1) is a unique surface protein of all apicomplexan parasites that plays a crucial role in parasite-host cell invasion and thus has been a long-standing malaria vaccine candidate. The selection of protective epitopes in silico has led to significant advances in the design of the vaccine. The present study aimed to employ bioinformatics tools to predict the potential immunogenic B- and T-cell epitopes in designing malaria vaccine targeting P. knowlesi AMA1 (PkAMA1). B-cell epitopes were predicted using four bioinformatics tools, i.e., BepiPred, ABCpred, BcePred, and IEDB servers whereas T-cell epitopes were predicted using two bioinformatics servers, i.e., NetMHCpan4.1 and NetMHCIIpan-4.0 targeting human major histocompatibility complex (MHC) class I and class II molecules, respectively. The antigenicity of the selected epitopes computed by both B- and T-cell predictors were further analyzed using the VaxiJen server. The results demonstrated that PkAMA1 protein encompasses multi antigenic regions that have the potential for the development of multi-epitope vaccine. Two B- and T-cell epitopes consensus regions, i.e., NSGIRIDLGEDAEVGNSKYRIPAGKCP (codons 28-54) and KTHAASFVIAEDQNTSY RHPAVYDEKNKT (codons 122-150) at domain I (DI) of PkAMA1 were reported. Advancement of bioinformatics in characterization of the target protein may facilitate vaccine development especially in vaccine design which is costly and cumbersome process. Thus, comprehensive B-cell and T-cell epitope prediction of PkAMA1 offers a promising pipeline for the development and design of multi-epitope vaccine against P. knowlesi.

Radiology teaching improves Anatomy scores for medical students.

OBJECTIVE: The aim of this study was to evaluate if small group teaching in Radiology impacted Anatomy scores in the summative end of year examination. METHODS: Small group teaching in Radiology was incorporated into Anatomy of year one medical students during the academic years 2016/17 and 2017/18. Examination outcome for 2 years before and 1 year after the study period were compared.Question papers for end of year summative examinations were retrieved; questions relating to Anatomy were identified and anonymised scores for students were obtained. RESULTS: Student numbers ranged 238 to 290/year. Mean Anatomy scores ranged 62-74%, this compared with mean total exam score of 62-65%. No significant difference in Anatomy and Total examination scores for 2015, 2016 and 2019. Mean (SD) Anatomy scores were significantly higher than the Total examination scores for the study period of 2017 and 2018 [68.97 (17.32) vs 63.12 (11.51) and 73.77 (17.85) vs 64.99 (10.31) (p < 0.001)]. Combined Anatomy scores 2017 and 2018 were significantly higher than 2015 and 2016, difference of 5.50 (95% C.I. 3.31-7.70; p < 0.001). CONCLUSION: This is the first study to objectively demonstrate Radiology small group teaching significantly improved Anatomy scores for medical students in the summative end of year examination. ADVANCES IN KNOWLEDGE: No evidence in the literature that Radiology teaching improves examination outcomes for medical students.This is the first study to directly link Radiology teaching with improved Anatomy examination result.Small group teaching in Radiology is a feasible way to teach Anatomy.

Undergraduate medical education: a national survey of consultant radiologists.

OBJECTIVE: Rising clinical demand and changes to Radiologists' job plans mean it is becoming ever more difficult for Radiologists to teach medical students.The aim of this study was to assess the current role of Radiologists in undergraduate medical education in Scotland. METHODS: Consultant Radiologists working across all 14 Scottish Health Boards were invited by email to participate in an anonymous short online survey. The survey ran for 6 weeks from November 2019. One reminder email was sent a week before the survey closed. RESULTS: 102 responses were recorded, representing 34% of the total whole time equivalent Radiologists in Scotland. All agreed Radiology should be taught to medical students. Over 70% (n = 73) taught medical students, most often during supporting professional activity time. 76 percent of Radiologists who did not teach expressed a desire to do so. The most common barrier to teaching was not having enough time in their job plan. Scottish Radiologists delivered a median of 10 h (IQR 0-22) a year of teaching to medical students. Thematic analysis of free comments revealed staffing/time constraints severely limiting ability to teach. CONCLUSION: This is the first national survey to assess the current role of Radiologists in teaching medical students. While most are teaching or want to teach, there is a large drop-off between current Scottish and previously reported UK median teaching hours. Engagement from Universities, Royal College of Radiologists and Health Boards is urgently needed to reverse this trend. ADVANCES IN KNOWLEDGE: This is the first national survey into the current role of Radiologists in undergraduate medical education. There is a large drop-off between current Scottish and previously reported UK median teaching hours.

Unexplained ascites, a sign for neuroendocrine carcinoma.

Neuroendocrine neoplasm is an epithelial neoplasm with predominant neuroendocrine differentiation that can arise from many organs in the body. We reported a rare case of gastric neuroendocrine carcinoma which accounts for less than 1% of all gastric tumours that is associated with poor prognosis. The recognition of this rare tumour in early stage is challenging and high suspicious into it might bring to early detection and so forth might improve the prognostication.

Réplica a «Tratamiento de la hiperuricemia asintomática» / Reply to «Treatment of asymptomatic hyperuricaemia»

No disponible

Measuring acute postoperative pain using the visual analog scale: the minimal clinically important difference and patient acceptable symptom state.

Background: The 100 mm visual analog scale (VAS) score is widely used to measure pain intensity after surgery. Despite this widespread use, it is unclear what constitutes the minimal clinically important difference (MCID); that is, what minimal change in score would indicate a meaningful change in a patient's pain status. Methods: We enrolled a sequential, unselected cohort of patients recovering from surgery and used a VAS to quantify pain intensity. We compared changes in the VAS with a global rating-of-change questionnaire using an anchor-based method and three distribution-based methods (0.3 sd , standard error of the measurement, and 5% range). We then averaged the change estimates to determine the MCID for the pain VAS. The patient acceptable symptom state (PASS) was defined as the 25th centile of the VAS corresponding to a positive patient response to having made a good recovery from surgery. Results: We enrolled 224 patients at the first postoperative visit, and 219 of these were available for a second interview. The VAS scores improved significantly between the first two interviews. Triangulation of distribution and anchor-based methods resulted in an MCID of 9.9 for the pain VAS, and a PASS of 33. Conclusions: Analgesic interventions that provide a change of 10 for the 100 mm pain VAS signify a clinically important improvement or deterioration, and a VAS of 33 or less signifies acceptable pain control (i.e. a responder), after surgery.

Ultrasonography in the diagnosis of asymptomatic hyperuricemia and gout.

Sonography has detected urate deposits in 34%-42% of the patients with asymptomatic hyperuricemia. This may prompt reclassification of asymptomatic hyperuricemia into "asymptomatic gout" and consideration of urate lowering therapy (ULT) to resolve urate deposits. In patients with gout and no visible tophi, sonography has detected urate deposits in half of the patients. This may allow diagnosing "tophaceous gout" and influencing the serum urate target level, prophylaxis to avoid acute gout flares during ULT, and clinical follow-up. Current accessibility to sonography may better classify patients with hyperuricemia and gout and contribute to delineate therapeutic objectives and clinical guidance.