Methicillin-resistant Staphylococcus aureus alters cell wall glycosylation to evade immunity.

Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of difficult-to-treat, often fatal infections in humans1,2. Most humans have antibodies against S. aureus, but these are highly variable and often not protective in immunocompromised patients3. Previous vaccine development programs have not been successful4. A large percentage of human antibodies against S. aureus target wall teichoic acid (WTA), a ribitol-phosphate (RboP) surface polymer modified with N-acetylglucosamine (GlcNAc)5,6. It is currently unknown whether the immune evasion capacities of MRSA are due to variation of dominant surface epitopes such as those associated with WTA. Here we show that a considerable proportion of the prominent healthcare-associated and livestock-associated MRSA clones CC5 and CC398, respectively, contain prophages that encode an alternative WTA glycosyltransferase. This enzyme, TarP, transfers GlcNAc to a different hydroxyl group of the WTA RboP than the standard enzyme TarS7, with important consequences for immune recognition. TarP-glycosylated WTA elicits 7.5-40-fold lower levels of immunoglobulin G in mice than TarS-modified WTA. Consistent with this, human sera contained only low levels of antibodies against TarP-modified WTA. Notably, mice immunized with TarS-modified WTA were not protected against infection with tarP-expressing MRSA, indicating that TarP is crucial for the capacity of S. aureus to evade host defences. High-resolution structural analyses of TarP bound to WTA components and uridine diphosphate GlcNAc (UDP-GlcNAc) explain the mechanism of altered RboP glycosylation and form a template for targeted inhibition of TarP. Our study reveals an immune evasion strategy of S. aureus based on averting the immunogenicity of its dominant glycoantigen WTA. These results will help with the identification of invariant S. aureus vaccine antigens and may enable the development of TarP inhibitors as a new strategy for rendering MRSA susceptible to human host defences.

Performance of two laser motion modes versus conventional orthodontic ceramic brackets debonding technique on enamel surface topography.

The risk of enamel deterioration that frequently coexists with debonding of orthodontic teeth brackets elevates the mandate for finding an optimum approach for debonding them without harmful effects. This in-vitro study is intended to compare the effects of two different laser modes (scanning and circular) and a conventional method on the enamel surface after debonding orthodontic brackets. 66 extracted premolars were assigned into 3 groups. After that, light-cure composite resin was used to attach the ceramic brackets to the teeth. Amongst the test groups, Group I: specimens that were debonded using conventional debonding using pliers; Group 2: specimens that were debonded using Er, Cr: YSGG laser applications using the circular motion method; and Group 3: specimens that were debonded using Er, Cr: YSGG laser applications using the scanning motion method. Adhesive Remnant Index (ARI) assessment, intra-pulpal temperature increase, enamel surface roughness after polishing, and assessment of the microstructure of enamel were carried out with scanning electron microscopy. The gathered information was examined statistically. The conventional debonding method had a significantly higher proportion of adhesive remnant index (ARI) scores of 2 and 3 in comparison to the circular (p < .004) and scanning laser groups (p < .001). There was no significant difference in ARI scores between the circular and scanning laser groups (p > .05). Moreover, the circular and scanning laser debonding methods resulted in a significantly higher proportion of Enamel Surface Roughness (ESR) scores of 0 and a lower proportion of ESR scores of 3 compared to the conventional technique group (p < .001). However, there was no significant difference in ESR scores between the circular and scanning laser methods (p = .945). Lastly, the average intra-pulpal temperature was significantly higher in the circular laser group (1.9 ± 0.5 ) compared to the scanning laser group (0.9 ± 0.2) with p < .001. Er, Cr: YSGG laser irradiation is a tool that shows promise for debonding ceramic brackets with minimal harm to the enamel surface. The scanning laser technique is more desirable due to the lower intra-pulpal temperature increase.

Accessibility crisis of essential medicines at Sudanese primary healthcare facilities: a cross-sectional drugs' dispensaries assessment and patients' perspectives.

BACKGROUND: Access to essential medicines is a critical component of universal health coverage. However, the availability of essential medicines in Sudan isn't well studied. As well, most Sudanese people lack health insurance, making out-of-pocket spending the primary source of drug financing. Therefore, the affordability of medicines in Sudan is questionable, with only 30% of the total population being covered by a public health service or public health insurance. We undertook this study to assess the availability and prices of essential medicines in public-sector health facilities in Khartoum state. Moreover, this study aims at assessing patients' perceived affordability of essential medicines, and accommodation and acceptability of the public facility. METHODS: A cross-sectional study was carried out at 30 primary healthcare facilities' drug dispensaries across three districts in Khartoum state. Within each Centre's dispensary unit, a standardized checklist evaluated the availability and affordability of 21 essential medicines selected from Sudan's national essential medicines list and assessed their storage conditions. Furthermore, 630 patients were selected from all dispensary units for an exit interview that assessed their perceived accessibility, acceptability, accommodation, and affordability of essential medicines. Data were collected through the Kobo toolbox and analyzed using SPSS version 26. RESULTS: Participants' ratings of accessibility, affordability, accommodation, and acceptability were 3.7/5, 1.5/4, 5/6, and 5.4/6, respectively, with a 26.7% full access and weak correlation between some of the indices. The overall availability of adults and pediatric medicines was 36.8% 6.7%, respectively. Cost of a single course of treatment for 10 and 16 drugs out of the 19 drugs consumed exceeds the daily wage of insured and uninsured patients, with a median price ratio of 16.4 and 62.8, respectively. Moreover, the dispensary area conditions were found to be of good quality, yet the storerooms were not functioning in 40% of the outlets. CONCLUSION: Patients had limited access to their needed drugs due to high prices and physical unavailability, and primary healthcare capacities are not meeting the demands of citizens. The outcomes for the patients' access variables (accessibility, accommodation, acceptance, and affordability) are comparable to those in countries with low incomes. Ensuring access to free medicines is likely to improve patients' satisfaction with healthcare services and reduce private expenditure on medicines, which is a long-term, sustainable way towards universal health coverage in Sudan.

Neuropsychiatric post-acute sequelae of COVID-19: prevalence, severity, and impact of vaccination.

The potential long-term neuropsychiatric effects of COVID-19 are of global concern. This study aimed to determine the prevalence and predictors of neuropsychiatric post-acute sequelae of COVID-19 among Egyptian COVID-19 survivors and to study the impact of full vaccination before COVID-19 infection on the occurrence and severity of these manifestations. Three months after getting COVID-19 infection, 1638 COVID-19 survivors were screened by phone for possible neuropsychiatric sequelae. Subjects suspected to suffer from these sequelae were invited to a face-to-face interview for objective evaluation. They were requested to rate the severity of their symptoms using visual analogue scales (VAS). The mean age of participants was 38.28 ± 13 years. Only 18.6% were fully vaccinated before COVID-19 infection. Neuropsychiatric post-acute sequelae of COVID-19 were documented in 598 (36.5%) subjects, fatigue was the most frequent one (24.6%), followed by insomnia (16.4%), depression (15.3%), and anxiety (14.4%). Moderate and severe COVID-19 infection and non-vaccination increased the odds of developing post-COVID-19 neuropsychiatric manifestations by 2 times (OR 1.95, 95% CI = 1.415-2.683), 3.86 times (OR 3.86, 95% CI = 2.358-6.329), and 1.67 times (OR 1.67, 95% CI = 1.253-2.216), respectively. Fully vaccinated subjects before COVID-19 infection (n = 304) had significantly lesser severity of post-COVID-19 fatigue, ageusia/hypogeusia, dizziness, tinnitus, and insomnia (P value = 0.001, 0.008, < 0.001, 0.025, and 0.005, respectively) than non-vaccinated subjects. This report declared neuropsychiatric sequelae in 36.5% of Egyptian COVID-19 survivors, fatigue being the most prevalent. The effectiveness of COVID-19 vaccines in reducing the severity of some post-COVID-19 neuropsychiatric manifestations may improve general vaccine acceptance.

Stroke in Pediatric Cancer Patients: A Systematic Review.

OBJECTIVE: Pediatric cancer patients have an increased risk of stroke. However, there is a knowledge gap regarding stroke in early stages of pediatric cancer. The objective of this project is to describe the current knowledge on stroke in pediatric cancer patients. DESIGN: Systematic review. MATERIALS AND METHODS: After Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, literature search was conducted in PubMed, Cochrane, and Google Scholar from January 1, 1995, up to February 1, 2022. RESULTS: A total of 3499 studies were identified, of which 8 met inclusion criteria. The incidence of stroke in pediatric cancer patients varied between 0.47% and 2.9%, and prevalence between 1% and 3%. The risk factors identified were leukemia diagnosis, cranial radiation, thrombocytopenia, coagulopathy, and infection. There was a higher rate of diagnosis with magnetic resonance imaging than with computed tomography scan. Treatment was inconsistent, and patients with cancer were less likely to receive antithrombotic treatment when compared with patients without cancer. The highest mortality was among hemorrhagic stroke. Recurrence rate was 5% to 19%. CONCLUSIONS: The risk for stroke is increased in the pediatric cancer population and can lead to devastating results. The available reports include few patients, with heterogeneous cancer diagnoses and outcomes. Large-scale multicenter studies are needed, focusing on early diagnosis, risk factors, and management strategies of stroke in children with underlying cancer.

Can fluorescence-guided surgery improve optimal surgical treatment for ovarian cancer? A systematic scoping review of clinical studies.

BACKGROUND: The predicament of achieving optimal surgical intervention faced by surgeons in treating ovarian cancer has driven research into improving intra-operative detection of cancer using fluorescent materials. OBJECTIVE: To provide a literature overview on the clinical use of intra-operative fluorescence-guided surgery for ovarian cancer, either for cytoreductive surgery or sentinel lymph node (SLN) biopsy. METHODS: The systematic review included studies from June 2002 until October 2021 from PubMed, Web of Science, and Scopus as well as those from a search of related literature. Studies were included if they investigated the use of fluorescence-guided surgery in patients with a diagnosis of ovarian cancer. Authors charted variables related to study characteristics, patient demographics, baseline clinical characteristics, fluorescence-guided surgery material, and treatment details, and surgical, oncological, and survival outcome variables. After screening 2817 potential studies, 24 studies were included. RESULTS: Studies investigating the role of fluorescence-guided surgery to visualize tumor deposits or SLN biopsy included the data of 410 and 118 patients, respectively. Six studies used indocyanine green tracer with a mean SLN detection rate of 92.3% with a pelvic and para-aortic detection rate of 94.8% and 96.7%, respectively. The sensitivity, specificity, and positive predictive value for micrometastases detection of OTL38 and 5-aminolevulinc acid at time of cytoreduction were 92.2% vs 79.8%, 67.3% vs 94.8%, and 55.8% vs 95.8%, respectively. CONCLUSION: Fluorescence -guided surgery is a technique that may improve the detection rate of micrometastases and SLN identification in ovarian cancer. Further research is needed to establish whether this will lead to improved patient outcomes.

Non-occupational physical activity and risk of cardiovascular disease, cancer and mortality outcomes: a dose-response meta-analysis of large prospective studies.

OBJECTIVE: To estimate the dose-response associations between non-occupational physical activity and several chronic disease and mortality outcomes in the general adult population. DESIGN: Systematic review and cohort-level dose-response meta-analysis. DATA SOURCES: PubMed, Scopus, Web of Science and reference lists of published studies. ELIGIBILITY CRITERIA: Prospective cohort studies with (1) general population samples >10 000 adults, (2) ≥3 physical activity categories, and (3) risk measures and CIs for all-cause mortality or incident total cardiovascular disease, coronary heart disease, stroke, heart failure, total cancer and site-specific cancers (head and neck, myeloid leukaemia, myeloma, gastric cardia, lung, liver, endometrium, colon, breast, bladder, rectum, oesophagus, prostate, kidney). RESULTS: 196 articles were included, covering 94 cohorts with >30 million participants. The evidence base was largest for all-cause mortality (50 separate results; 163 415 543 person-years, 811 616 events), and incidence of cardiovascular disease (37 results; 28 884 209 person-years, 74 757 events) and cancer (31 results; 35 500 867 person-years, 185 870 events). In general, higher activity levels were associated with lower risk of all outcomes. Differences in risk were greater between 0 and 8.75 marginal metabolic equivalent of task-hours per week (mMET-hours/week) (equivalent to the recommended 150 min/week of moderate-to-vigorous aerobic physical activity), with smaller marginal differences in risk above this level to 17.5 mMET-hours/week, beyond which additional differences were small and uncertain. Associations were stronger for all-cause (relative risk (RR) at 8.75 mMET-hours/week: 0.69, 95% CI 0.65 to 0.73) and cardiovascular disease (RR at 8.75 mMET-hours/week: 0.71, 95% CI 0.66 to 0.77) mortality than for cancer mortality (RR at 8.75 mMET-hours/week: 0.85, 95% CI 0.81 to 0.89). If all insufficiently active individuals had achieved 8.75 mMET-hours/week, 15.7% (95% CI 13.1 to 18.2) of all premature deaths would have been averted. CONCLUSIONS: Inverse non-linear dose-response associations suggest substantial protection against a range of chronic disease outcomes from small increases in non-occupational physical activity in inactive adults. PROSPERO registration number CRD42018095481.

Recurrent brachial plexopathy as initial presentation of systemic lupus erythematosus: A case report and review of the literature.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects many organs of the body including the peripheral nervous system (PNS) which has potential significant impact. Plexopathy is rare but one of the serious PNS manifestations of lupus. CASE: A 41-year-old female presented with recurrent attacks of painful brachial plexopathy and right hemi-diaphragmatic paralysis. After extensive workup, she was diagnosed with SLE and started on hydroxychloroquine and mycophenolate mofetil. The frequency and severity of the attacks of plexopathy has significantly improved after starting the immune suppressive therapy for SLE. Whole exome sequencing unveiled previously unreported mutations encoding non-synonymous amino acids in titin and minichromosome maintenance 3-associated protein. CONCLUSION: Recurrent attacks of painful brachial plexopathy may warrant careful evaluation for underlying SLE with a premise of therapeutic benefit.

Characteristics and progression of childhood-onset and adult-onset eosinophilic esophagitis.

BACKGROUND AND AIM: The prevalence and incidence of eosinophilic esophagitis (EoE) has been increasing over recent years. However, the natural history remains incompletely understood particularly the differences in disease characteristics and progression of childhood-onset and adult-onset EoE. The aim of this study was to evaluate the disease characteristics and progression of childhood-onset and adult-onset EoE. METHODS: A cross-sectional, questionnaire-based study, on 87 adults and 67 children from 2 major tertiary hospitals in South Australia was conducted. Data of those who were diagnosed with EoE between 1999 and 2018 were collected and correlated with medical records. RESULTS: Of the 87 adults with EoE, 34 (39%) were diagnosed at the age of < 18 years (childhood-onset EoE). Reflux symptoms were more common in childhood-onset EoE, whereas asthma was more common in adult-onset EoE. The median duration of symptoms prior to diagnosis of EoE was > 1-4 years in childhood-onset disease (44%) and ≥ 10 years in adult-onset disease (34%). Food impaction was significantly more common on initial presentation in those with adult-onset EoE, whereas weight loss was more common in childhood-onset EoE. At the time of questionnaire, regurgitation, abdominal pain, and bloating were more common in childhood-onset EoE. Those with childhood-onset EoE were more likely to have multiple symptoms at questionnaire when compared with their adult-onset counterparts. In both groups, 15% (5/34 childhood-onset EoE and 8/53 adult-onset EoE) were asymptomatic at the time of questionnaire. CONCLUSION: Childhood-onset EoE appears to be a progressive disease from childhood to adulthood, however with more inflammatory-type symptoms post transition compared to those with adult-onset EoE.

Sleep disturbance in cancer patients referred to an ambulatory integrative oncology consultation.

BACKGROUND: Sleep disturbance (SD) is highly prevalent in oncology and negatively affects quality of life and mortality. Evidence supports the use of integrative oncology (IO) practices to treat SD, but there is limited published data on the characteristics of SD and factors associated with SD in IO. We determined the prevalence, severity, and factors associated with SD among cancer patients seen in an ambulatory IO consultation. METHODS: Patients with cancer referred for initial outpatient IO consultation in 2017 were eligible. Patient demographics, clinical characteristics, and patient-reported outcomes (Edmonton Symptom Assessment Scale (ESAS), Measure Yourself Concerns and Wellbeing (MYCaW), PROMIS-10) were retrospectively reviewed. RESULTS: One thousand five hundred twenty patients were included in the analysis. The majority (70%) were women with breast cancer (42%). Nine hundred seventy-one (64%) patients reported significant SD with ESAS Sleep ≥ 4, yet only 11% expressed poor sleep as their primary or secondary concern for the IO consultation. The median SD (IQR) was 5 (3,7). ESAS scores for fatigue (adjusted OR 1.16; CI 1.07-1.26, p < 0.001), pain (adjusted OR 1.07; CI 1.00-1.15, p < 0.05), hot flashes (adjusted OR 1.14; CI 1.07-1.22, p < 0.001), well-being (adjusted OR 1.33; CI 1.22-1.46, p < 0.001), and psychological distress score (anxiety and depression) (adjusted OR 1.16; CI 1.01-1.11, p < 0.01) were independently associated with SD in multivariate analysis. Acupuncture was the most frequent intervention prescribed, 175 (35%). Other modalities included oncology massage (15%), health psychology (5%), and meditation (1%). CONCLUSIONS: Although 64% of patients seeking IO consultation reported clinically significant SD, only 11% were seeking integrative approaches for managing SD. ESAS fatigue, hot flashes, well-being, and psychological symptoms were significantly associated with SD.

Etiology, clinical characteristics, and outcome of infective endocarditis: 10-year experience from a tertiary care center in Pakistan.

This study was conducted to assess the clinical characteristics, causative agents, complications, and outcomes of infective endocarditis (IE) among patients presenting to our tertiary care center over the last decade. This retrospective cohort study included all adult patients admitted to the Aga Khan University Hospital with the diagnosis of IE over a ten-year period from 2010 to 2020.  Outcomes variables included complications during hospitalization, surgical intervention, mortality, and length of stay. We identified a total of 305 cases out of which 176 (58%) were males and 129 (42%) were females. The mean age of the patients was 46.9±18.8 years. 95 (31%) had prosthetic valves in place. Staphylococcus aureus was isolated in 54 (39%) patients followed by coagulase-negative Staphylococcus in 23 (17%). Echocardiography revealed vegetations and abscesses in 236 (77%) and 4 (1%) patients, respectively. The most common valvular complication was mitral valve regurgitation found in 26 (9%) patients, followed by tricuspid valve regurgitation in 13 (4%) patients and aortic valve regurgitation in 11 (3%) patients. Furthermore, 81 (27%) patients suffered from heart failure and 66 (22%) from a stroke during hospitalization. The mean hospital length of stay was 10.4 ± 10.6 days. 64 (21%) patients required surgical repair and the overall mortality rate was 25%. Prosthetic valve endocarditis (OR = 3.74, 95% CI = 2.15-6.50, p<0.001), chronic kidney disease (OR = 2.51, 95% CI = 1.15-5.47, p=0.036), previous stroke (OR = 2.42, 95% CI = 1.18-4.96, p=0.026), and ischemic heart disease (OR = 3.04, 95% CI = 1.50-6.16, p=0.003) were significantly associated with an increased risk of mortality. In conclusion, our study provided valuable data on the clinical characteristics and outcomes of patients with IE in a developing country. S. aureus was the most common causative agent. Heart failure and stroke were the most common complications. The presence of prosthetic valves, history of chronic kidney disease, ischemic heart disease and previous stroke were associated with a significantly increased risk of mortality. Surgical management was not associated with improved outcomes.

Role of Mosque Communities in Supporting Muslims with Mental Illness: Results of CBPR-oriented Focus Groups in the Bay Area, California.

Objective The purpose of this study was to explore perspectives of Muslims residing in the Bay Area, California on the role of the mosque community in supporting community members' mental health needs and barriers to mental health care for members who experience mental health challenges. Methods This study employed a CBPR-focused qualitative approach in the form of content analysis of three focus group discussions organized and conducted with the help of a Community Advisory Board made up of members of the Muslim Community Association. Results Two major themes were identified upon examination of the data: services needed in the mosque community and barriers to addressing mental health issues in the mosque community. Specifically, participants reported wanting support groups within the mosque space, mosque-based activities, virtual support, community social workers, and family-oriented services. Barriers reported included community stigma, lack of cultural awareness of race-ethnic minorities within the community, attribution of mental illness to lack of faith or supernatural causes, and specific barriers unique to vulnerable/special subgroups within the community. Conclusion These findings highlight the need for developing mental health-related services and social support initiatives within the mosque space, specifically for those Muslim Americans living in the Bay Area in California. Furthermore, special attention needs to be placed on the barriers to accessing these services as identified by the community members.

Post-COVID-19 neuropsychiatric manifestations among COVID-19 survivors suffering from migraine: a case-control study.

BACKGROUND: The burden of post-coronavirus disease (COVID)-19 symptoms has been increasing and is of great concern in patients with pre-existing chronic medical conditions.This study aimed to delineate the post-COVID-19 neuropsychiatric symptoms among migraine patients compared to the non-migraine control group. METHODS: Two groups, each of 204 COVID-19 survivors, were enrolled in the study after 3 months of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, one group fulfilling the episodic migraine criteria and the other serving as a matching control group. Subjects were evaluated through an in-person interview for post-COVID-19 neuropsychiatric symptoms, including detailed headache patterns and severity, using the visual analogue scale. RESULTS: The Frequency of headache during the acute phase of COVID-19 was more frequent in migraine patients (OR = 1.60, 95%CI = 1.04-2.45, P-value = 0.031). The reported significant post-COVID-19 neuropsychiatric symptoms in migraine patients compared to controls were fatigue (OR = 1.662, 95%CI = 1.064-2.596, P-value = 0.025), anosmia/hyposmia (OR = 2.06, 95%CI = 1.164- 3.645, P-value = 0.012), cacosmia (OR = 2.663, 95%CI = 1.145-6.195, P-value = 0.019), depression (OR = 2.259, 95%CI = 1.284- 3.975, P-value = 0.004), anxiety (OR = 3.267, 95%CI = 1.747- 6.108, P-value ≤ 0.001), insomnia (OR = 2.203, 95%CI = 1.298- 3.739, P-value = 0.003), and headache (OR = 3.148, 95%CI = 1.616-6.136, P-value = ≤ 0.001).While there was no statistically significant difference between migraine patients and controls regarding the post-COVID-19 functional status score (P-value = 0.102). The pattern of post-COVID-19 headache was reported as chronic headache transformation in 17.6% of the migraine group, with the median intensity rate being 5.5 and IQR (3-7). In the control group, 14% experienced chronic headache attributed to systemic viral infection with a median intensity rate of 2 and IQR (2-5), while 12% experienced a new daily persistent headache with a median intensity of 5 and IQR (1-6). CONCLUSION: The study highlighted the importance of follow-up migraine patients upon recovery from COVID-19 infection, being more vulnerable to post-COVID-19 symptoms.

Knowledge and practice of ethics among postgraduates in a public sector tertiary care hospital.

OBJECTIVE: To explore the present state of competency in clinical ethics among postgraduate trainees in a tertiary care hospital. METHODS: The interview-based cross-sectional study was conducted at the Civil Hospital, Karachi, from September 2018 to March 2019, and comprised postgraduate trainees of either gender in any year of the training programme across all specialties. Data was collected using self-reported questionnaire seeking opinion about present working conditions regarding clinical ethical issues on the hospital ground and problems they face from day to day. Data was analysed using SPSS 23. RESULTS: Of the 153 subjects, 96(62.7%) were females, 73(47.7%) were from Medicine and allied disciplines, and 80(52.3%) were from Surgery and allied disciplines. The primary source of their clinical ethics' understanding was derived from their workplace [116(75.82%)]. While only 104 (68%) of the subjects knew about the Hippocratic Oath's contents, less than 10% knew about Nuremberg Code and Helsinki declaration. They mainly relied on their seniors at work for guidance on ethical issues [108 (70.59%)]. Overall, the subjects lacked basic knowledge of medical ethics and failed to practise ethical conduct during their training. CONCLUSIONS: The knowledge of medical ethics was found to be unsatisfactory among doctors, and timely intervention was needed to improve the situation.

Bleeding Risk and Mortality Associated With Uninterrupted Antithrombotic Therapy During Percutaneous Endoscopic Gastrostomy Tube Placement.

INTRODUCTION: Antithrombotic therapy is often interrupted before the placement of a percutaneous endoscopic gastrostomy (PEG) tube because of potentially increased risk of hemorrhagic events. The aim of our study was to evaluate the risk of bleeding events and overall complication rates after PEG in patients on uninterrupted antiplatelet and anticoagulation therapy in a high-volume center. METHODS: Data regarding demographics, diagnoses, comorbidities, and clinical outcomes pertinent to PEG were collected from 2010 to 2016. Furthermore, data regarding antithrombotic therapy along with the rate of minor or major complications including bleeding associated with this procedure were analyzed. Significant bleeding was defined as postprocedure bleeding from PEG site requiring a blood transfusion and/or surgical/endoscopic intervention. RESULTS: We included 1,613 consecutive PEG procedures in this study, of which 1,540 patients (95.5%) received some form of uninterrupted antithrombotic therapy. Of those patients, 535 (34.7%) were on aspirin, 256 (16.6%) on clopidogrel, and 119 (7.7%) on both aspirin and clopidogrel. Subcutaneous heparin was uninterrupted in 980 (63.6%), intravenous heparin in 34 (2.1%), warfarin in 168 (10.9%), and direct-acting oral anticoagulation in 82 (5.3%) patients who overlapped on multiple drugs. We observed 6 significant bleeding events in the entire cohort (0.39%), and all were in subcutaneous heparin groups either alone or in combination with aspirin. No clinically significant bleeding was noted in patients on uninterrupted aspirin, warfarin, clopidogrel, or direct-acting oral anticoagulation groups. Only 5 patients (0.31%) had PEG-related mortality. DISCUSSION: The risk of significant bleeding associated with the PEG placement was minimal in patients on uninterrupted periprocedural antithrombotic therapy.

(Automated) Synthesis of Well-defined Staphylococcus Aureus Wall Teichoic Acid Fragments.

Wall teichoic acids (WTAs) are important components of the cell wall of the opportunistic Gram-positive bacterium Staphylococcus aureus. WTAs are composed of repeating ribitol phosphate (RboP) residues that are decorated with d-alanine and N-acetyl-d-glucosamine (GlcNAc) modifications, in a seemingly random manner. These WTA-modifications play an important role in shaping the interactions of WTA with the host immune system. Due to the structural heterogeneity of WTAs, it is impossible to isolate pure and well-defined WTA molecules from bacterial sources. Therefore, here synthetic chemistry to assemble a broad library of WTA-fragments, incorporating all possible glycosylation modifications (α-GlcNAc at the RboP C4; ß-GlcNAc at the RboP C4; ß-GlcNAc at the RboP C3) described for S. aureus WTAs, is reported. DNA-type chemistry, employing ribitol phosphoramidite building blocks, protected with a dimethoxy trityl group, was used to efficiently generate a library of WTA-hexamers. Automated solid phase syntheses were used to assemble a WTA-dodecamer and glycosylated WTA-hexamer. The synthetic fragments have been fully characterized and diagnostic signals were identified to discriminate the different glycosylation patterns. The different glycosylated WTA-fragments were used to probe binding of monoclonal antibodies using WTA-functionalized magnetic beads, revealing the binding specificity of these WTA-specific antibodies and the importance of the specific location of the GlcNAc modifications on the WTA-chains.

Metabolomic Profiling and Neuroprotective Effects of Purslane Seeds Extract Against Acrylamide Toxicity in Rat's Brain.

AIM: Acrylamide (ACR) is an environmental pollutant with well-demonstrated neurotoxic and neurodegenerative effects in both humans and experimental animals. The present study aimed to investigate the neuroprotective effect of Portulaca oleracea seeds extract (PSE) against ACR-induced neurotoxicity in rats and its possible underlying mechanisms. PSE was subjected to phytochemical investigation using ultra-high-performance liquid chromatography (UPLC) coupled with quantitative time of flight mass spectrometry (qTOF-MS). Multivariate, clustering and correlation data analyses were performed to assess the overall effects of PSE on ACR-challenged rats. Rats were divided into six groups including negative control, ACR-intoxicated group (10 mg/kg/day), PSE treated groups (200 and 400 mg/kg/day), and ACR + PSE treated groups (200 and 400 mg/kg/day, respectively). All treatments were given intragastrically for 60 days. PSE markedly ameliorated brain damage as evidenced by the decreased lactate dehydrogenase (LDL), increased acetylcholinesterase (AchE) activities, as well as the increased brain-derived neurotrophic factor (BDNF) that were altered by the toxic dose of ACR. In addition, PSE markedly attenuated ACR-induced histopathological alterations in the cerebrum, cerebellum, hippocampus and sciatic nerve and downregulated the ACR-inclined GFAP expression. PSE restored the oxidative status in the brain as indicated by glutathione (GSH), lipid peroxidation and increased total antioxidant capacity (TAC). PSE upregulated the mRNA expression of protein kinase B (AKT), which resulted in an upsurge in its downstream cAMP response element-binding protein (CREB)/BDNF mRNA expression in the brain tissue of ACR-intoxicated rats. All exerted PSE beneficial effects were dose-dependent, with the ACR-challenged group received PSE 400 mg/kg dose showed a close clustering to the negative control in both unsupervised principal component analysis (PCA) and supervised orthogonal partial least square discriminant analysis (OPLS-Da) alongside with the hierarchical clustering analysis (HCA). The current investigation confirmed the neuroprotective capacity of PSE against ACR-induced brain injury, and our findings indicate that AKT/CREB pathways and BDNF synthesis may play an important role in the PSE-mediated protective effects against ACR-triggered neurotoxicity.

Pseudoachalasia: a diagnostic challenge. When to consider and how to manage?

Pseudoachalasia accounts for up to 4% of patients who present with achalasia-like picture and most often relates to occult malignancy at the cardia or gastroesophageal junction. Thus, any delay in diagnosis might lead to more advanced disease and less chance for curative therapy, not to mention the risk of serious complications resulting from the treatment of supposed achalasia instead of the true underlying cause. The entity should be suspected in patients with advanced age of onset, a shorter duration of symptoms, profound weight loss and difficulty in passing the gastroesophageal junction on endoscopy. The diagnosis of pseudoachalasia can be challenging as upper endoscopy with biopsy might be false negative in 25% of cases and lesions cannot always be detected on computerized tomography scan. Endoscopic ultrasound and guided biopsy play an increasingly important role in the workup of this condition. Treatment of pseudoachalasia depends on the underlying cause. The aim of this review is to highlight the clinicopathological features that distinguish pseudoachalasia from achalasia and the most appropriate diagnostic workup as well as the subsequent management for this condition.

Interventions for replacing missing teeth: alveolar ridge preservation techniques for dental implant site development.

BACKGROUND: Alveolar bone changes following tooth extraction can compromise prosthodontic rehabilitation. Alveolar ridge preservation (ARP) has been proposed to limit these changes and improve prosthodontic and aesthetic outcomes when implants are used. This is an update of the Cochrane Review first published in 2015. OBJECTIVES: To assess the clinical effects of various materials and techniques for ARP after tooth extraction compared with extraction alone or other methods of ARP, or both, in patients requiring dental implant placement following healing of extraction sockets. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 19 March 2021), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2021, Issue 2), MEDLINE Ovid (1946 to 19 March 2021), Embase Ovid (1980 to 19 March 2021), Latin American and Caribbean Health Science Information database (1982 to 19 March 2021), Web of Science Conference Proceedings (1990 to 19 March 2021), Scopus (1966 to 19 March 2021), ProQuest Dissertations and Theses (1861 to 19 March 2021), and OpenGrey (to 19 March 2021). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. A number of journals were also handsearched. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) on the use of ARP techniques with at least six months of follow-up. Outcome measures were: changes in the bucco-lingual/palatal width of alveolar ridge, changes in the vertical height of the alveolar ridge, complications, the need for additional augmentation prior to implant placement, aesthetic outcomes, implant failure rates, peri-implant marginal bone level changes, changes in probing depths and clinical attachment levels at teeth adjacent to the extraction site, and complications of future prosthodontic rehabilitation. DATA COLLECTION AND ANALYSIS: We selected trials, extracted data, and assessed risk of bias in duplicate. Corresponding authors were contacted to obtain missing information. We estimated mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes, with 95% confidence intervals (95% CI). We constructed 'Summary of findings' tables to present the main findings and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 16 RCTs conducted worldwide involving a total of 524 extraction sites in 426 adult participants. We assessed four trials as at overall high risk of bias and the remaining trials at unclear risk of bias. Nine new trials were included in this update with six new trials in the category of comparing ARP to extraction alone and three new trials in the category of comparing different grafting materials. ARP versus extraction: from the seven trials comparing xenografts with extraction alone, there is very low-certainty evidence of a reduction in loss of alveolar ridge width (MD -1.18 mm, 95% CI -1.82 to -0.54; P = 0.0003; 6 studies, 184 participants, 201 extraction sites), and height (MD -1.35 mm, 95% CI -2.00 to -0.70; P < 0.0001; 6 studies, 184 participants, 201 extraction sites) in favour of xenografts, but we found no evidence of a significant difference for the need for additional augmentation (RR 0.68, 95% CI 0.29 to 1.62; P = 0.39; 4 studies, 154 participants, 156 extraction sites; very low-certainty evidence) or in implant failure rate (RR 1.00, 95% CI 0.07 to 14.90; 2 studies, 70 participants/extraction sites; very low-certainty evidence). From the one trial comparing alloplasts versus extraction, there is very low-certainty evidence of a reduction in loss of alveolar ridge height (MD -3.73 mm; 95% CI -4.05 to -3.41; 1 study, 15 participants, 60 extraction sites) in favour of alloplasts. This single trial did not report any other outcomes. Different grafting materials for ARP: three trials (87 participants/extraction sites) compared allograft versus xenograft, two trials (37 participants, 55 extraction sites) compared alloplast versus xenograft, one trial (20 participants/extraction sites) compared alloplast with and without membrane, one trial (18 participants, 36 extraction sites) compared allograft with and without synthetic cell-binding peptide P-15, and one trial (30 participants/extraction sites) compared alloplast with different particle sizes. The evidence was of very low certainty for most comparisons and insufficient to determine whether there are clinically significant differences between different ARP techniques based on changes in alveolar ridge width and height, the need for additional augmentation prior to implant placement, or implant failure. We found no trials which evaluated parameters relating to clinical attachment levels, specific aesthetic or prosthodontic outcomes for any of the comparisons. No serious adverse events were reported with most trials indicating that the procedure was uneventful. Among the complications reported were delayed healing with partial exposure of the buccal plate at suture removal, postoperative pain and swelling, moderate glazing, redness and oedema, membrane exposure and partial loss of grafting material, and fibrous adhesions at the cervical part of previously preserved sockets, for the comparisons xenografts versus extraction, allografts versus xenografts, alloplasts versus xenografts, and alloplasts with and without membrane. AUTHORS' CONCLUSIONS: ARP techniques may minimise the overall changes in residual ridge height and width six months after extraction but the evidence is very uncertain. There is lack of evidence of any differences in the need for additional augmentation at the time of implant placement, implant failure, aesthetic outcomes, or any other clinical parameters due to lack of information or long-term data. There is no evidence of any clinically significant difference between different grafting materials and barriers used for ARP. Further long-term RCTs that follow CONSORT guidelines (www.consort-statement.org) are necessary.

Does acute stress disorder predict posttraumatic stress disorder following workplace violence? A prospective study of psychiatric staff.

OBJECTIVES: Psychiatric staff is at risk of workplace violence (WV) and subsequent posttraumatic symptomatology. The current study assesses the prevalence of acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) in psychiatric staff following WV. This also examines the prospective association between ASD and PTSD. METHODS: This is a prospective cohort study of staff from 18 psychiatric wards in Denmark (n = 250), that reported an incident of workplace violence. RESULTS: The prevalence of ASD was 10.8%, while 8% had PTSD 3 months post-assault. Generalized linear mixed models showed a significant predictive power of ASD on PTSD (OR 8.45, p < 0.001) in the fully adjusted model. CONCLUSIONS: ASD seems to be a predictor of future PTSD in an occupational context and should be considered a possible instrument in enactment of preventive strategies.