Maternal plasma soluble neuropilin-1 is downregulated in fetal growth restriction complicated by abnormal umbilical artery Doppler: a pilot study.

OBJECTIVES: Placental expression of neuropilin-1 (NRP1), a proangiogenic member of the vascular endothelial growth factor receptor family involved in sprouting angiogenesis, was recently discovered to be downregulated in pregnancies with fetal growth restriction (FGR) and abnormal umbilical artery (UA) Doppler. Soluble NRP1 (sNRP1) is an antagonist to NRP1; however, little is known about its role in normal and FGR pregnancies. This study tested the hypotheses that, first, sNRP1 would be detectable in maternal circulation and, second, its concentration would be upregulated in FGR pregnancies compared to those with normal fetal growth and this would correlate with the severity of the disease as assessed by UA Doppler. METHODS: This was a prospective case-control pilot study of 40 singleton pregnancies (20 FGR cases and 20 uncomplicated controls) between 24 + 0 and 40 + 0 weeks' gestation followed in an academic perinatal center from January 2015 to May 2017. FGR was defined as an ultrasound-estimated fetal weight < 10th percentile for gestational age. The control group was matched to the FGR group for maternal age and gestational age at assessment. Fetal ultrasound biometry and UA Doppler were performed using standard protocols. Maternal plasma sNRP1 measurements were performed using a commercially available ELISA. RESULTS: Contrary to the study hypothesis, maternal plasma sNRP1 levels were significantly decreased in FGR pregnancies as compared to those with normal fetal growth (137.4 ± 44.8 pg/mL vs 166.7 ± 36.9 pg/mL; P = 0.03). However, there was no significant difference in sNRP1 concentration between the control group and FGR pregnancies that had normal UA Doppler. Plasma sNRP1 was downregulated in FGR pregnancies with elevated UA systolic/diastolic ratio (P = 0.023) and those with UA absent or reversed end-diastolic flow (P = 0.005) in comparison to FGR pregnancies with normal UA Doppler. This suggests that biometrically small fetuses without hemodynamic compromise are small-for-gestational age rather than FGR. CONCLUSIONS: This study demonstrated a significant decrease in maternal plasma sNRP1 concentration in growth-restricted pregnancies with fetoplacental circulatory compromise. These findings suggest a possible role of sNRP1 in modulating fetal growth and its potential as a biomarker for FGR. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Regenerative medicine, organ bioengineering and transplantation.

BACKGROUND: Organ transplantation is predicted to increase as life expectancy and the incidence of chronic diseases rises. Regenerative medicine-inspired technologies challenge the efficacy of the current allograft transplantation model. METHODS: A literature review was conducted using the PubMed interface of MEDLINE from the National Library of Medicine. Results were examined for relevance to innovations of organ bioengineering to inform analysis of advances in regenerative medicine affecting organ transplantation. Data reports from the Scientific Registry of Transplant Recipient and Organ Procurement Transplantation Network from 2008 to 2019 of kidney, pancreas, liver, heart, lung and intestine transplants performed, and patients currently on waiting lists for respective organs, were reviewed to demonstrate the shortage and need for transplantable organs. RESULTS: Regenerative medicine technologies aim to repair and regenerate poorly functioning organs. One goal is to achieve an immunosuppression-free state to improve quality of life, reduce complications and toxicities, and eliminate the cost of lifelong antirejection therapy. Innovative strategies include decellularization to fabricate acellular scaffolds that will be used as a template for organ manufacturing, three-dimensional printing and interspecies blastocyst complementation. Induced pluripotent stem cells are an innovation in stem cell technology which mitigate both the ethical concerns associated with embryonic stem cells and the limitation of other progenitor cells, which lack pluripotency. Regenerative medicine technologies hold promise in a wide array of fields and applications, such as promoting regeneration of native cell lines, growth of new tissue or organs, modelling of disease states, and augmenting the viability of existing ex vivo transplanted organs. CONCLUSION: The future of organ bioengineering relies on furthering understanding of organogenesis, in vivo regeneration, regenerative immunology and long-term monitoring of implanted bioengineered organs.

Longitudinal Associations Among Posttraumatic Stress Disorder, Disordered Eating, and Weight Gain in Military Men and Women.

Obesity is a major health problem in the United States and a growing concern among members of the military. Posttraumatic stress disorder (PTSD) has been associated with overweight and obesity and may increase the risk of those conditions among military service members. Disordered eating behaviors have also been associated with PTSD and weight gain. However, eating disorders remain understudied in military samples. We investigated longitudinal associations among PTSD, disordered eating, and weight gain in the Millennium Cohort Study, which includes a nationally representative sample of male (n = 27,741) and female (n = 6,196) service members. PTSD at baseline (time 1; 2001-2003) was associated with disordered eating behaviors at time 2 (2004-2006), as well as weight change from time 2 to time 3 (2007-2008). Structural equation modeling results revealed that the association between PTSD and weight change from time 2 to time 3 was mediated by disordered eating symptoms. The association between PTSD and weight gain resulting from compensatory behaviors (vomiting, laxative use, fasting, overexercise) was significant for white participants only and for men but not women. PTSD was both directly and indirectly (through disordered eating) associated with weight change. These results highlight potentially important demographic differences in these associations and emphasize the need for further investigation of eating disorders in military service members.

Pancreatic neuroendocrine tumors in twelve baboons (Papio spp.).

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are rare in nonhuman primates and in humans. METHODS: Twenty-one PNETs from twelve female baboons (Papio spp.) from the Southwest National Primate Research Center were evaluated using histopathology and immunohistochemistry. RESULTS: Histologically, all tumors were benign and had neuroendocrine packeting. Immunohistochemical staining for synaptophysin and chromogranin was positive in all tumors evaluated (17/17). Insulin was positive in 16 of 21 tumors. Somatostatin was positive in 9 of 20 tumors. Multifocal staining for glucagon and pancreatic polypeptide was evident in a minority of tumors (6/20 and 2/17, respectively). Gastrin and vasoactive intestinal peptide were negative in all tumors evaluated. Nine tumors expressed more than one hormone marker. CONCLUSIONS: This is the first detailed pathologic study of pancreatic endocrine tumors in the baboon. The findings suggest that these tumors are generally benign and have similar morphologic and immunohistochemical features as those described in people, including the ability to express multiple hormones.

Dimensions of wisdom perception across twelve countries on five continents.

Wisdom is the hallmark of social judgment, but how people across cultures recognize wisdom remains unclear-distinct philosophical traditions suggest different views of wisdom's cardinal features. We explore perception of wise minds across 16 socio-economically and culturally diverse convenience samples from 12 countries. Participants assessed wisdom exemplars, non-exemplars, and themselves on 19 socio-cognitive characteristics, subsequently rating targets' wisdom, knowledge, and understanding. Analyses reveal two positively related dimensions-Reflective Orientation and Socio-Emotional Awareness. These dimensions are consistent across the studied cultural regions and interact when informing wisdom ratings: wisest targets-as perceived by participants-score high on both dimensions, whereas the least wise are not reflective but moderately socio-emotional. Additionally, individuals view themselves as less reflective but more socio-emotionally aware than most wisdom exemplars. Our findings expand folk psychology and social judgment research beyond the Global North, showing how individuals perceive desirable cognitive and socio-emotional qualities, and contribute to an understanding of mind perception.

Testing for urinary tract colonization before high-dose corticosteroid treatment in acute multiple sclerosis relapses: prospective algorithm validation.

BACKGROUND AND PURPOSE: To evaluate a dipstick algorithm for urinary tract colonization, prior to high-dose corticosteroid treatment in acute relapses of multiple sclerosis (MS). METHODS: Prospective cohort study of 267 consecutive patients with MS relapses requiring corticosteroid treatment in a hospital-based, ambulatory, acute MS relapse clinic. A total of 18 participants met the exclusion criteria, leaving 249 for analysis. Main outcome measures were urinary dipstick sensitivity, specificity, positive predictive value, negative predictive value and safety of antibiotic co-treatment with high-dose corticosteroids. RESULTS: Significant bacteriuria (≥10(5) colonies ml) rate in this population was 11% (95% CI, 7.1-14.9). Specificity and sensitivity of positive leucocyte esterase or nitrite were 78% and 65%. Negative predictive value of urine dipstick was 96%. No clinical adverse events occurred in the 3% (95% CI, 0.9-5.1) of patients with a false-negative dipstick. Eighteen per cent of patients were unnecessarily treated with antibiotics for 48 h. CONCLUSION: Urinary dipstick testing allows for rapid and safe management of patients suffering from an acute MS relapse. The algorithm is conservative, and future work is needed to reduce the false-positive rate.

A qualitative exploration of a financial inclusion service in an English foodbank.

AIMS: Foodbanks provide emergency food provision. This need can be triggered by a change in circumstance or a crisis. Failures in the social security safety net are the most significant driver for hunger in the UK. There is some evidence that an advisory service which runs alongside a foodbank is more effective in reducing emergency provision and the duration and severity of hunger. The 'Making a Difference' project at an English foodbank is a pilot scheme aiming to increase financial resilience in their service users. From summer 2022, they introduced new advice worker roles, in partnership with Shelter [Housing advice] and Citizen's Advice [General, debt and benefits advice], aiming to pre-empt the need for foodbank use, to triage the financial needs of service users and refer appropriately to reduce repeat visits to the foodbank. METHODS: This qualitative study involved in-depth interviews with four staff and four volunteers to evaluate barriers, facilitators and potential friction points in referrals and partnership working. FINDINGS: Our data were analysed thematically into four themes: Holistic needs assessment; Reaching seldom heard communities; Empowerment; The needs of staff and volunteers. Two case studies illustrate the complexity of people's needs. CONCLUSION: A financial inclusion service operating within foodbanks giving housing, debt and benefits advice shows some promise in reaching people in crisis at the point of need. Based within the heart of a community, it appears to meet the complex needs of very vulnerable people who may have found mainstream support services inaccessible. This asset-based approach with the foodbank as a trusted provider enabled joined up, compassionate, holistic, and person-centred advice quickly cutting across multiple agencies, reaching underserved and socially excluded clients. We suggest that supportive services are needed for volunteers and staff who are vulnerable to vicarious trauma from listening and supporting people in crisis.

We care but we're not carers: perceptions and experiences of social prescribing in a UK national community organisation.

AIMS: (1) To explore how social prescribing referrals impact experiences of existing members of a voluntary and community-based organisation and (2) to describe the processes and relationships associated with joining community and voluntary organisations. METHODS: Online survey and qualitative interviews with members of Men's Sheds, a global volunteer-led initiative to address loneliness and social isolation in men. 93 self-selecting Shed members (average age 67 years, 93% male) from across England and Scotland took part in the survey about demographics, joining the Shed, and free-text questions about experiences in the Shed. From the survey participants, 21 Shed members were purposively sampled and interviewed to explore the impact of social prescribing and referrals on the Sheds. RESULTS: Participating in the Men's Shed was often associated with a significant change in personal circumstances, and Sheds provided a unique social support space, particularly valuable for men. Key factors around experiences of social prescribing and referral mechanisms were identified. We developed three themes: the experience of joining a Shed, success factors and risks of social prescribing, and 'we care but we're not carers'. CONCLUSIONS: The results show that Men's Sheds are a caring organisation, but their members are not trained as professional carers, and men come to the Shed for their own personal reasons. They are concerned about the potential additional responsibilities associated with formal referrals. They encourage the development of relationships and local-level understanding of the essence of Sheds to enable social prescribing. As models of social prescribing grow nationally and internationally, collaboratively working with voluntary and community organisations to develop a mutually beneficial approach is essential for the effectiveness and sustainability of social prescribing in community health.

Toxoplasmosis in ring-tailed lemurs (Lemur catta) and a peahen (Pavo cristatus) in a zoological collection caused by the common toxoplasma genotype in wild animals in the US.

Toxoplasmosis is caused by the ubiquitous Apicomplexan protozoan Toxoplasma gondii. This pathogen affects domestic and wildlife species, but prosimians including ring-tailed lemurs (Lemur catta) are highly susceptible to infection with high mortality rates. Avian species are considered resistant to infection and are often used in surveillance efforts to determine genotypes of T. gondii present in geographical areas. This study describes the gross and histologic lesions of an outbreak of toxoplasmosis in a university-run zoological collection involving three ring-tailed lemurs and a peahen (Pavo cristatus). DNA was extracted from the liver of the lemurs and peahen to determine the genotype of T. gondii by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), which revealed that all samples were ToxoDB PCR-RFLP genotype #5 (haplogroup 12) that is common in wildlife in North America.

Development and certification of green tea-containing standard reference materials.

A suite of three green tea-containing Standard Reference Materials (SRMs) has been issued by the National Institute of Standards and Technology (NIST): SRM 3254 Camellia sinensis (Green Tea) Leaves, SRM 3255 Camellia sinensis (Green Tea) Extract, and SRM 3256 Green Tea-Containing Solid Oral Dosage Form. The materials are characterized for catechins, xanthine alkaloids, theanine, and toxic elements. As many as five methods were used in assigning certified and reference values to the constituents, with measurements carried out at NIST and at collaborating laboratories. The materials are intended for use in the development and validation of new analytical methods, and for use as control materials as a component in the support of claims of metrological traceability.

The effects of electronic polarization on water adsorption in metal-organic frameworks: H2O in MIL-53(Cr).

The effects of electronic polarization on the adsorption of water in the MIL-53(Cr) metal-organic framework are investigated using molecular dynamics simulations. For this purpose a fully polarizable force field for MIL-53(Cr) was developed which is compatible with the ab initio-based TTM3-F water model. The analysis of the spatial distributions of the water molecules within the MIL-53(Cr) nanopores calculated as a function of loading indicates that polarization effects play an important role in the formation of hydrogen bonds between the water molecules and the hydroxyl groups of the framework. As a result, large qualitative differences are found between the radial distribution functions calculated with non-polarizable and polarizable force fields. The present analysis suggests that polarization effects can significantly impact molecular adsorption in metal-organic frameworks under hydrated conditions.

Sclerosing cholangitis in baboons (Papio spp) resembling primary sclerosing cholangitis of humans.

Primary sclerosing cholangitis is a chronic and progressive cholestatic liver disease that has been extensively documented in the human literature. Although it shares many features in common with chronic lymphocytic cholangitis in cats, primary sclerosing cholangitis has never been reported in a nonhuman primate. Primary sclerosing cholangitis is characterized by the presence of intrahepatic and/or extrahepatic inflammation and concentric fibrosis of bile ducts, eventually leading to cirrhosis and hepatic failure. The pathogenesis and cause remain unknown, but the disease likely involves a multifactorial mechanism with genetic- and immune-mediated components. The authors report 2 cases that histologically resemble the condition in humans; they consist of 2 adult male baboons with a clinical history of chronic elevated liver enzymes. In both cases, the liver was histologically characterized by thick bands of fibrosis and mild lymphoplasmacytic periportal cholangiohepatitis with concentric periductal fibrosis, resulting in atrophy and loss of bile ducts. Immunohistochemical analysis revealed positivity of hepatocytes to cytokeratin 7. Masson stain demonstrated marked biliary fibrosis. This is the first report that resembles sclerosing cholangitis in a nonhuman primate, and it suggests that the baboon may provide a useful animal model for this condition in humans.

Natural Heterobilharzia americana infection in horses in Texas.

The schistosome Heterobilharzia americana infects dogs, raccoons, and other mammals in the southeastern United States. Migration of eggs into the liver results in parasitic granulomas with varying degrees of fibrosis and inflammation. Recently, hepatic parasitic granulomas in horses were shown to be caused by H. americana infection. In the present study, samples of liver from 11 of 12 horses with hepatic granulomas identified at necropsy (n = 11) or surgical biopsy (n = 1) were used for DNA extraction, polymerase chain reaction amplification and sequencing using primers specific for a portion of the H. americana small subunit ribosomal RNA gene. A polymerase chain reaction amplicon of the correct size was produced from the extracted DNA in 8 of the 11 horses. Amplicons from 5 of the 8 positive horses were sequenced and had 100% identity with H. americana. In all but 2 of the 12 horses, Heterobilharzia was not responsible for the primary clinical disease, and the hepatic granulomas were considered an incidental finding.

Pancarditis as the sole clinical manifestation of protothecosis in a Boxer dog.

A 4.2-year-old, male castrated Boxer was diagnosed with a dilated cardiomyopathy phenotype, complex arrhythmias and left-sided congestive heart failure, but died suddenly shortly after initial diagnostics were complete. Ultrasensitive cardiac troponin I was markedly elevated (9.345 ng/mL [reference range: 0-0.06 ng/mL]), and a Trypanosoma cruzi immunofluorescent antibody titer was positive at 1:80. Necropsy revealed a severe, necrotizing, histiocytic, lymphoplasmacytic pancarditis with intralesional algae consistent with protothecosis, as well as evidence of left-sided congestive heart failure. Algal organisms were found only in the heart. Acute Chagas disease was not thought to play a role given the lack of T. cruzi amastigotes on postmortem and negative reverse transcription polymerase chain reaction testing on formalin fixed, paraffin embedded myocardium, however a possible contribution of chronic Chagas disease to the clinical picture could not be ruled out. Canine protothecosis is typically a disseminated disease. This case represents the first report of canine protothecosis limited solely to the heart.

What can we Learn from Patients who Died from Covid-19 Following Escalation to a Respiratory High Dependency Unit for Trial of Non-Invasive Respiratory Support?

Background: Covid-19 infection is associated with significant risk of death, particularly in older, comorbid patients. Emerging evidence supports use of non-invasive respiratory support (CPAP and high-flow nasal oxygen [HFNO]) in this context, but little is known about its use in patients receiving end-of-life care. Methods: This was a retrospective study of 33 patients who died of Covid-19 on the Respiratory High Dependency Unit at the John Radcliffe Hospital, Oxford between 28/03/20 and 20/05/20. Data was sourced via retrospective review of electronic patient records and drug charts. Results: Patients dying from Covid-19 on the Respiratory HDU were comorbid with median Charlson Comorbidity Index 5 (IQR 4-6); median age 78 (IQR 72-85). Respiratory support was trialled in all but one case with CPAP being the most common form of first line respiratory support (84.8%) however, was only tolerated in 44.8% of patients. Median time to death was 10.7 days from symptom onset (IQR 7.5-14.6) and 4.9 days from hospital admission (IQR 3.1-8.3). 48.5% of patients remained on respiratory support at the time of death. Conclusions: End-of-life care for patients with Covid-19 remains a challenge. Patients tend to be frail and comorbid with a rapid disease trajectory. Non-Invasive Respiratory Support may play a key role in symptom management in select patients, however, further work is needed in order to identify patients who will most benefit from Respiratory Support and those for whom withdrawal may prevent unnecessary distress at the end of life or potential prolongation of suffering.

Certification of vitamins and carotenoids in SRM 3280 multivitamin/multielement tablets.

A new multivitamin/multielement dietary supplement Standard Reference Material (SRM) has been issued by the National Institute of Standards and Technology (NIST), with certified and reference concentration values for 13 vitamins, 24 elements, and 2 carotenoids. The constituents have been measured by multiple analytical methods with data contributed by NIST and by collaborating laboratories. This effort included the first use of isotope dilution mass spectrometry for value assignment of both fat-soluble vitamins (FSVs) and water-soluble vitamins (WSVs). Excellent agreement was obtained among the methods, with relative expanded uncertainties for the certified concentration values typically ranging from <2% to 15% for vitamins.

Equine rhabdomyolysis.

A 1.5-year-old Quarter Horse gelding with a history of chronic nasal discharge and leukocytosis presented with signs of increased lethargy and muscular pain. The horse quickly became recumbent and unable to rise and was euthanized due to a poor prognosis. At necropsy, severe bilateral guttural pouch empyema was observed, as well as numerous well-demarcated areas of pallor within the skeletal muscles of all major muscle groups. Polymerase chain reaction testing of the guttural pouch exudate confirmed an infection with Streptococcus equi subsp. equi, and an S. equi-associated immune-mediated rhabdomyolysis was initially considered to be the most likely diagnosis. This report briefly discusses the various etiologies that should be considered in cases of equine myopathy, and it demonstrates the complexity of these poorly understood muscular disorders.

Pathology of GM2 gangliosidosis in Jacob sheep.

The G(M2) gangliosidoses are a group of lysosomal storage diseases caused by defects in the genes coding for the enzyme hexosaminidase or the G(M2) activator protein. Four Jacob sheep from the same farm were examined over a 3-year period for a progressive neurologic disease. Two lambs were 6-month-old intact males and 2 were 8-month-old females. Clinical findings included ataxia in all 4 limbs, proprioceptive deficits, and cortical blindness. At necropsy, the nervous system appeared grossly normal. Histologically, most neurons within the brain, spinal cord, and peripheral ganglia were enlarged, and the cytoplasm was distended by foamy to granular material that stained positively with Luxol fast blue and Sudan black B stains. Other neuropathologic findings included widespread astrocytosis, microgliosis, and scattered spheroids. Electron microscopy revealed membranous cytoplasmic bodies within the cytoplasm of neurons. Biochemical and molecular genetic studies confirmed the diagnosis of G(M2) gangliosidosis. This form of G(M2) gangliosidosis in Jacob sheep is very similar to human Tay-Sachs disease and is potentially a useful animal model.

Management of problems related to the new morbidity by community-based paediatricians in Israel.

OBJECTIVES: To assess community-based paediatricians' management of clinical situations, particularly those related to the new morbidity (NM), such as chronic disease, developmental, behavioural, and psychosocial problems, and to identify the main associated factors. METHODS: The study population included all community-based paediatricians employed by Israel's two largest health maintenance organizations in the central and southern regions of the country (n= 574; 74% response rate). Using a self-administered questionnaire including 20 vignettes describing common clinical situations (14 related to NM; 6 related to classic paediatrics (CP)), physicians reported how they would manage each situation and how they perceived their role in managing such problems. RESULTS: Paediatricians were less likely to take an active role in managing NM-related problems than CP-related problems (68.3% vs. 93.2%; P < 0.001). In most NM situations, when paediatricians regarded the problem as part of their role, they were more likely to either manage the problem by themselves or with the help of other professionals. A multivariable linear regression model, adjusting for demographic, practice and training characteristics indicated the following predictive factors for taking an active role in managing NM (P < 0.001): practicing in the periphery, consulting with non-medical community-based professionals and combining community and hospital practice. CONCLUSIONS: To assure comprehensive paediatric care, simultaneous modification of paediatricians' residency training, practice environment and role perception are required.