Probable IGG4 related ophthalmic disease presenting with uveitis.

We present a case of an uncommon presentation of IgG4-related ophthalmic disease (ROD). A 58-year-old female presented with unilateral acute anterior uveitis of the right eye, which progressed to scleritis with the development of an associated orbital mass despite treatment with oral glucocorticoid. Initial histopathology of an orbital biopsy was non-diagnostic and continued progression of the disease lead to complete loss of vision in the right eye. The development of uveitis in the previously unaffected left eye led to the decision for enucleation of the right globe and further orbital biopsy. Histopathology revealed features supporting IgG4-related ophthalmic disease. Oral glucocorticoid therapy failed to induce remission, and rituximab therapy was initiated, leading to a rapid resolution in her symptoms. Other cases with a similar presentation report a poor visual prognosis, highlighting the need for prompt diagnosis and treatment of uveitis associated with signs of orbital or scleral involvement.

Four cases of myocarditis in US hospitals possibly associated with clozapine poor metabolism and a comparison with prior published cases.

Objectives: Clozapine-induced myocarditis may be a hypersensitivity reaction due to titration that was too rapid for a patient's clozapine metabolism. Obesity, infections, and inhibitors (e.g., valproate) may lead to clozapine poor metabolizer (PM) status. The hypothesis that 4 patients with clozapine-induced myocarditis from two United States hospitals were clozapine PMs was tested by studying their minimum therapeutic clozapine doses and titrations. Methods: Using methodology from a prior myocarditis case series of 9 Turkish patients, we studied: 1) the concentration-to-dose (C/D) ratio; 2) minimum therapeutic dose required to reach 350 ng/ml (a marker for PM status); and 3) titration speed. Results: All 4 patients were possible clozapine PMs (their respective minimum therapeutic doses were: 134, 84, 119 and 107 mg/day). The identified possible contributors to clozapine PM status were: 1) valproate in Cases 1, 2 and 4; 2) obesity and a urinary tract infection in Case 2; and 3) obesity and very rapid titration in Case 4. Case 3, who was given a normal US titration, appeared to be a genetic clozapine PM. He developed clozapineinduced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome after rechallenge using 12.5 mg/day > 3 months later. The results were similar to 9 Turkish cases, all of which were PMs (6 on valproate, 4 with obesity, 1 with infection and 1 possibly genetic). Conclusions: Future studies using clozapine levels and considering the role of clozapine PM status should explore whether or not all cases of clozapine-induced myocarditis could be explained by lack of individualized titration. (Neuropsychopharmacol Hung 2022; 24(1): 29-41).

New Onset Alacrima as a Presenting Feature of a Skull Base Chondrosarcoma.

Acquired unilateral alacrima as a presenting sign of an intracranial tumor is exceptionally rare, and only described once previously in a case of nasopharyngeal carcinoma. The authors present a 32-year-old female patient who presents with a year-long history of alacrima and arhinorrhea. She was subsequently diagnosed with a petroclival chondrosarcoma extending into Meckel's cave and the cavernous sinus and underwent surgical debulking. To the authors' knowledge, this is the first reported case of acquired unilateral alacrima as a presenting feature of a skull base chondrosarcoma. This case serves to remind general ophthalmologists and oculoplastic surgeons alike that acquired alacrima may be the presenting feature of serious intracranial disease.

Assessment of the risk of needlestick injuries associated with intravitreal injections.

PURPOSE: To assess the overall risk of needlestick injuries (NSIs) associated with intravitreal injection, and more specifically related to the practice of compounding pharmacies of applying informational adhesive stickers to repackaged bevacizumab injection syringes. METHODS: This cross-sectional study involved an online survey of retina specialists in the United States. RESULTS: Of the 717 invited retina specialists, 158 (22%) responded to the online survey. The respondents reported using 1 pair of gloves (51%), no gloves (46%), or 2 pairs of gloves (3%) during intravitreal injection. Repackaged bevacizumab syringes distributed by compounding pharmacy were used by 89% of the respondents, and 63% reported that the adhesive sticker was applied directly to the syringe. Unintentional adhesion between the sticker and hand or glove was experienced by 9% of respondents. At least 1 NSI during intravitreal injection was experienced by 8% of respondents, and sticker-related injury was reported by 3%. The sticker was perceived to increase risk for NSI by 33% of respondents. CONCLUSION: This survey showed that 8% of the responding physicians surveyed have experienced at least one NSI during intravitreal injections, of which approximately one third was attributed to the adhesive sticker. Direct application of misfitting stickers to repackaged syringes by compounding pharmacies may be a practice that can aggravate the risk of NSI.

"My Dead Body": Development, production, and reception of a documentary that publicly displays the dissection of a human donor.

Recently, there has been an emphasis on keeping the study of anatomy using donor material confined to the domain of medical and allied healthcare professionals. Given the abundance of both accurate and inaccurate information online, coupled with a heightened focus on health following the COVID-19 pandemic, one may question whether it is time to review who can access learning anatomy using donors. In 2019, Brighton and Sussex Medical School (BSMS) obtained a Human Tissue Authority Public Display license with the aim of broadening the reach of who could be taught using donor material. In 2020, BSMS received its first full-body donor with consent for public display. Twelve workshops were delivered to student groups who do not normally have the opportunity to learn in the anatomy laboratory. Survey responses (10.9% response rate) highlighted that despite being anxious about seeing inside a deceased body, 95% felt more informed about the body. A documentary "My Dead Body" was filmed, focusing on the rare cancer of the donor Toni Crews. Viewing figures of 1.5 million, and a considerable number of social media comments highlighted the public's interest in the documentary. Thematic analysis of digital and social media content highlighted admiration and gratitude for Toni, the value of education, and that while the documentary was uncomfortable to watch, it had value in reminding viewers of life, their bodies, and their purpose. Fully consented public display can create opportunities to promote health-conscious life choices and improve understanding of the human body.

Histopathological features of asymmetric lacrimal gland enlargement in patients with thyroid eye disease.

PURPOSE: Lacrimal gland enlargement can be a feature of thyroid eye disease (TED). Unilateral or asymmetric lacrimal gland enlargement is poorly described and may impede diagnosis. We present the histological and clinical findings of four patients with asymmetric lacrimal gland enlargement. METHODS: A retrospective case note review was performed for patients over two tertiary orbital clinics (Royal Adelaide Hospital, South Australia and the Sussex Eye Hospital, Brighton, United Kingdom) presenting with an asymmetrical lacrimal gland enlargement with a background of TED that underwent biopsy to exclude alternate diagnoses. Baseline data was collected for each patient and histopathological images and reports were reviewed. RESULTS: All four patients were hyperthyroid at time of lacrimal gland biopsy. Biopsy demonstrated nonspecific, lymphoid aggregates, typically of B cell type, with no diagnostic findings to support lymphocyte clonality or IgG4-related disease. One biopsy specimen demonstrated evidence of some fibrosis. CONCLUSION: Asymmetrical lacrimal gland enlargement can occur as part of the TED spectrum but may require biopsy to exclude alternate pathology. Histology demonstrates a non-specific lymphocytic infiltrate.

The consequences of unintended births for maternal and child health in India.

Data from the Indian National Family Health Survey, 2005-06 were used to explore how pregnancy intention at the time of conception influences a variety of maternal and child health and health care outcomes. Results indicate that mistimed children are more likely than wanted children to be delivered without a skilled attendant present (OR = 1.3), to not receive all recommended vaccinations (OR = 1.4), and to die during the neonatal and postneonatal periods (OR = 1.8 and 2.6, respectively). Unwanted children are more likely than wanted children to not receive all recommended vaccinations (OR = 2.2), to be stunted (OR = 1.3), and to die during the neonatal, postneonatal, and early childhood periods (OR = 2.2, 3.6, and 5.9, respectively). Given the high levels of unintended fertility in India (21 per cent of all births), these are striking findings that underscore the importance of investments in family planning.

A large-scale study of respiratory virus infection over 2 years using the Luminex xTAGRVP assay.

Traditional methods of detecting and identifying respiratory viruses like cell culture and immunofluorescence are labor intensive, often slow, and are dependent on specimen viability. As a result, there has been a shift in laboratory practices from these methods to molecular-based techniques such as polymerase chain reaction, which can be faster, more sensitive, and less labor intensive than traditional methods. The Food and Drug Administration approved version of the Luminex xTAG respiratory viral panel (RVP) assay detects 12 respiratory viruses simultaneously. We evaluated the performance of the RVP assay, on over 8,000 nasopharyngeal specimens during a 2-year period. Approximately 70% of all specimens tested were positive for at least one respiratory virus. Influenza A (Inf A) was the most prevalent, followed by respiratory syncytial virus. The RVP assay also detected the newly emerging Inf A porcine H1N1 that started to circulate in 2008. However, it could not identify it to subtype level and required further confirmatory tests. This study shows that the RVP assay is an invaluable tool in monitoring seasonal outbreaks and pandemic events. It not only detects newly emerging influenza strains, but also allows the throughput of thousands of clinical specimens in a timely manner, reducing the turnaround time from weeks to days, when compared to cell culture.

Topographical anatomy of the annulus of Zinn.

The anatomy and even existence of a common tendinous origin of the extraocular eye muscles, or annulus of Zinn, has widely been debated in anatomical literature. This study explored the anatomical origins of the recti muscles, their course into the orbit and the dural connections of the common tendinous origin with the skull base. Twenty orbits of ten adult human cadavers were dissected. The orbital apex and its dural connections were photographed. Histological examination of apical specimens was performed. In all cadavers, extraocular muscles were observed to have a common tendinous origin at the orbital apex, continuous with dural connections extending into the skull base. Accessory slips of the medial rectus were observed across all cadavers. Dual heads of the lateral rectus were observed in fourteen orbits of seven cadavers. The origin of the levator palpebrae superioris appeared to be contiguous with the superior rectus at the common tendinous origin in all but one cadaver. These results support the existence of a common tendinous origin of the extraocular muscles, that is continuous with the skull base dura. In addition, they support the existence of variations in orbital anatomy including dual or accessory muscle slips of the extraocular muscles.

High resolution dataset from a net-zero home that demonstrates zero-carbon living and transportation capacity.

This dataset includes high resolution, detailed end use data from a net-zero occupied home that demonstrates zero-carbon living and transportation capacity. The house is located in Davis, California, U.S., and the dataset includes full year data from 2020 with 1 minute time resolution. The data has been monitored with more than 230 sensors installed in the house, and there are total 332 channels available. The data includes detailed end use electricity data (e.g., HVAC system, lighting, plug load including major appliances), building's interior thermal conditions (e.g., indoor air temperatures in multiple rooms and relative humidity), HVAC system operation data (e.g., soil temperatures around ground bores and supply water temperatures), on-site power generation system data (e.g., PV power supply and PV surface temperatures) and etc. The original dataset from the house has been curated, and the data has been carefully reviewed for quality check. The data quality check revealed there are 156 minutes of data were missing in the month of April, and around 1,404 minutes of data was missing in August. The data gap was filled with linear interpolation in case the gap is less than continuous 6 hours. Otherwise, the data is filled with -9999. The data curation has been processed using the Tsdat framework (https://github.com/tsdat/tsdat). In addition, a semantic description for the dataset was generated by leveraging the Brick (https://brickschema.org/). The final curated and processed data as well as raw data are currently available through https://bbd.labworks.org/ds/bbd/hshus.

Physical violence by partner during pregnancy and use of prenatal care in rural India.

The role of physical violence during pregnancy on receipt of prenatal care is poorly understood, particularly for South Asian countries that have high levels of both fertility and domestic violence. Data from the 1998/1999 Indian National Family Health Survey and a 2002/2003 follow-up survey that re-interviewed women in four states were analyzed, examining the association between physical violence during pregnancy and the uptake of prenatal care. Women who experienced physical violence during pregnancy were less likely to receive prenatal care, less likely to receive a home-visit from a health worker for a prenatal check-up, less likely to receive at least three prenatal care visits, and less likely to initiate prenatal care early in the pregnancy. This study highlighted the constraining effect that the experience of physical domestic violence during pregnancy had on the uptake of prenatal care for women in rural India. Maternal health services must recognize the unique needs of women experiencing violence from their intimate partners.

Measurement of and trends in unintended birth in Bangladesh, 1983-2000.

Bangladesh has experienced a rapid decline in fertility in the past several decades, facilitated by proactive population policies, provision of contraceptives, and broader societal shifts, encouraging smaller families and use of contraceptive to achieve revised childbearing norms. This paper presents 18 years of data from the Sample Registration System, a demographic surveillance system operated by the Maternal and Child Health-Family Planning Extension Project in six study areas in Bangladesh. Prospective measurements of women's fertility preferences were used for classifying nearly 25,000 birth outcomes from 1983 to 2000 as intended, unintended, or 'up to God/Allah'. Over the 18-year period, the level of unintended births varied from 22% to 38%, with the lowest levels in the mid-1990s. Fatalistic responses declined significantly from 25% in the mid-1980s to 1% by the late 1990s. Results of the comparison of two geographic areas of Bangladesh indicate differential declines in the levels of unintended pregnancies over the study period. Prospective measurements of unintended pregnancies were 2-3 times the magnitude indicated by retrospective estimates of unwanted births from the demographic and health surveys conducted during the study period. This unique dataset provides a rare opportunity to visualize the vast changes in fertility preferences and unintended births in Bangladesh from 1983 to 2000. Significant declines in fatalistic responses reflect broader social changes that occurred in Bangladesh to facilitate the fertility decline and contraceptive uptake. The drastic differences between prospective and retrospective measurements of fertility preferences highlight the importance of considering the strengths and limitations of each method when attempting to estimate the true level of unintended pregnancies and births in a population.

Pooling Nasopharyngeal Swab Specimens to Increase Testing Capacity for SARS-CoV-2.

The recent emergence of SARS-CoV-2 has led to a global pandemic of unprecedented proportions. Current diagnosis of COVID-19 relies on the detection of SARS-CoV-2 RNA by reverse transcription polymerase chain reaction (RT-PCR) in upper and lower respiratory specimens. While sensitive and specific, these RT-PCR assays require considerable supplies and reagents, which are often limited during global pandemics and surge testing. Here, we show that a nasopharyngeal swab pooling strategy can detect a single positive sample in pools of up to 10 samples without sacrificing RT-PCR sensitivity and specificity. We also report that this pooling strategy can be applied to rapid, moderate complexity assays, such as the BioFire COVID-19 test. Implementing a pooling strategy can significantly increase laboratory testing capacity while simultaneously reducing turnaround times for rapid identification and isolation of positive COVID-19 cases in high risk populations.

3D printed ceramics as solid supports for enzyme immobilization: an automated DoE approach for applications in continuous flow.

In recent years, 3D printing has emerged in the field of chemical engineering as a powerful manufacturing technique to rapidly design and produce tailor-made reaction equipment. In fact, reactors with complex internal geometries can be easily fabricated, optimized and interchanged in order to respond to precise process needs, such as improved mixing and increased surface area. These advantages make them interesting especially for catalytic applications, since customized structured bed reactors can be easily produced. 3D printing applications are not limited to reactor design, it is also possible to realize functional low cost alternatives to analytical equipment that can be used to increase the level of process understanding while keeping the investment costs low. In this work, in-house designed ceramic structured inserts printed via vat photopolymerization (VPP) are presented and characterized. The flow behavior inside these inserts was determined with residence time distribution (RTD) experiments enabled by in-house designed and 3D printed inline photometric flow cells. As a proof of concept, these structured inserts were fitted in an HPLC column to serve as solid inorganic supports for the immobilization of the enzyme Phenolic acid Decarboxylase (bsPAD), which catalyzes the decarboxylation of cinnamic acids. The conversion of coumaric acid to vinylphenol was chosen as a model system to prove the implementation of these engineered inserts in a continuous biocatalytic application with high product yield and process stability. The setup was further automated in order to quickly identify the optimum operating conditions via a Design of Experiments (DoE) approach. The use of a systematic optimization, together with the adaptability of 3D printed equipment to the process requirements, render the presented approach highly promising for a more feasible implementation of biocatalysts in continuous industrial processes. Graphical abstract. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41981-021-00163-4.

STK11/LKB1 Loss of Function Is Associated with Global DNA Hypomethylation and S-Adenosyl-Methionine Depletion in Human Lung Adenocarcinoma.

STK11 (liver kinase B1, LKB1) is the fourth most frequently mutated gene in lung adenocarcinoma, with loss of function observed in up to 30% of all cases. Our previous work identified a 16-gene signature for LKB1 loss of function through mutational and nonmutational mechanisms. In this study, we applied this genetic signature to The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples and discovered a novel association between LKB1 loss and widespread DNA demethylation. LKB1-deficient tumors showed depletion of S-adenosyl-methionine (SAM-e), which is the primary substrate for DNMT1 activity. Lower methylation following LKB1 loss involved repetitive elements (RE) and altered RE transcription, as well as decreased sensitivity to azacytidine. Demethylated CpGs were enriched for FOXA family consensus binding sites, and nuclear expression, localization, and turnover of FOXA was dependent upon LKB1. Overall, these findings demonstrate that a large number of lung adenocarcinomas exhibit global hypomethylation driven by LKB1 loss, which has implications for both epigenetic therapy and immunotherapy in these cancers. SIGNIFICANCE: Lung adenocarcinomas with LKB1 loss demonstrate global genomic hypomethylation associated with depletion of SAM-e, reduced expression of DNMT1, and increased transcription of repetitive elements.

The routine use of histochemical stains in gastrointestinal pathology: a UK-wide survey.

AIMS: A survey was conducted into the routine use of special stains on gastrointestinal (GI) biopsy specimens in histopathology departments within the National Health Service. The aim was to compare the sole use of haematoxylin and eosin (H&E) staining with the use of H&E and special stains, according to the biopsy site. METHODS AND RESULTS: One hundred and sixty-seven histopathology departments in the UK were contacted using an e-mail questionnaire. Valid return rate was 55%. Sixty-eight percent of departments employ H&E only for oesophageal biopsy specimens. Gastric specimens are stained using only H&E in 47% of departments and 53% use H&E combined with special stains. Duodenal, small and large bowel biopsy specimens are mostly stained with H&E. CONCLUSIONS: The results show that the routine use of special stains in GI pathology in the UK is highly variable, especially for oesophageal and gastric biopsy specimens. The literature indicates that special stains in GI specimens can enhance sensitivity and specificity for the detection of pathological abnormalities, especially metaplasia and infections. The diversity of staining practice highlights the need to provide robust and evidence-based guidelines for the routine use of special stains to ensure universal best practice.

Alcohol use, intimate partner violence, sexual coercion and HIV among women aged 15-24 in Rakai, Uganda.

Disinhibition due to alcohol may induce intimate partner violence and sexual coercion and increased risk of HIV infection. In a sample of 3,422 women aged 15-24 from the Rakai cohort, Uganda, we examined the association between self-reported alcohol use before sex, physical violence/sexual coercion in the past and prevalent HIV, using adjusted odds ratios (Adj OR) and 95% confidence intervals (95% CI). During the previous year, physical violence (26.9%) and sexual coercion (13.4%) were common, and alcohol use before sex was associated with a higher risk of physical violence/sexual coercion. HIV prevalence was significantly higher with alcohol consumption before sex (Adj OR = 1.45, 95% CI: 1.06-1.98) and especially when women reported both prior sexual coercion and alcohol use before sex (Adj OR = 1.79, 95% CI: 1.25-2.56). Alcohol use before sex was associated with physical violence and sexual coercion, and both are jointly associated with HIV infection risk in young women.

Women's satisfaction with delivery care in Nairobi's informal settlements.

OBJECTIVE: To quantify women's satisfaction with delivery care in informal settlements of Nairobi, Kenya, and to determine characteristics of women and delivery care associated with satisfaction. DESIGN: Household survey data analysis of 1266 women who delivered in health facilities in 2004 or 2005. SETTING: Two densely populated informal settlements 7 and 12 km from Nairobi's center, where residents work primarily in the nearby industrial area or in the informal sector. Outcome Satisfaction was assessed by whether women would recommend the delivery care facility and deliver there again. RESULTS: Over half (56%) of women would both recommend and deliver again in the same facility. In multivariate analysis, women's satisfaction with delivery care was associated with greater provider empathy (OR = 3.68, 95% CI 2.27, 5.97). Women's satisfaction with delivery care was also associated with the pregnancy having been wanted (OR = 2.75, 95% CI 1.82, 4.14) or mistimed vs. unwanted. Women delivering at private facilities in the settlement near the industrial area were more satisfied than women delivering at private facilities in the more distant and marginalized settlement (OR = 2.12, 95% CI 1.45, 3.09). The association of women's satisfaction and provider empathy was stronger among women who experienced complications compared to those who did not. CONCLUSION: Health providers should be sensitized to the finding that unintended pregnancy is associated with lower satisfaction with delivery care. Maternal health programmes should focus on increasing provider empathy, especially for women who experience complications, in both private and government health facilities.

Fecal containment in bedridden patients: economic impact of 2 commercial bowel catheter systems.

BACKGROUND: Fecal contamination is a major challenge in patients in acute/critical care settings that is associated with increased cost of care and supplies and with development of pressure ulcers, incontinence dermatitis, skin and soft tissue infections, and urinary tract infections. OBJECTIVES: To assess the economic impact of fecal containment in bedridden patients using 2 different indwelling bowel catheters and to compare infection rates between groups. METHODS: A multicenter, observational study was done at 12 US sites (7 that use catheter A, 5 that use catheter B). Patients were followed from insertion of an indwelling bowel catheter system until the patient left the acute/critical care unit or until 29 days after enrollment, whichever came first. Demographic data, frequency of bedding/dressing changes, incidence of infection, and Braden scores (risk of pressure ulcers) were recorded. RESULTS: The study included 146 bedridden patients (76 with catheter A, 70 with catheter B) who had similar Braden scores at enrollment. The rate of bedding/dressing changes per day differed significantly between groups (1.20 for catheter A vs 1.71 for catheter B; P = .004). According to a formula that accounted for personnel resources and laundry cycle costs, catheter A cost $13.94 less per patient per day to use than did catheter B. Catheter A was less likely than was catheter B to be removed during the observational period (P = .03). Observed infection rates were low. CONCLUSION: Catheter A may be more cost-effective than catheter B because it requires fewer unscheduled linen changes per patient day.