Miracle-dz/UniFAR-FTUs huggingface dataset:
Proof of principle: Physiological transfer of small numbers of bacteria from mother to fetus in late-gestation pregnant sheep

Fetal development is thought to proceed in a sterile environment. Recent reports of the presence of bacterial DNA in human placenta, the transfer of live bacteria from mother to fetus after hypoxia in the pregnant sheep, and the presence of bacteria in the meconium of newborn infants have suggested that the fetus might be exposed to bacteria in utero. The present experiments were designed to test the hypothesis that small numbers of bacteria introduced into the maternal bloodstream (too few to induce fever or changes in maternal food consumption), can be found in the fetus days later. We injected 100 colony forming units of green-, red- and far red- fluorescent protein (GFP, RFP, FRFP) expressing S. aureus into late-gestation pregnant sheep intravenously. Five to 7 days later, the animals were euthanized and tissues collected for analysis of GFP. The inoculations did not cause any fever or other measurable behavioral response in the ewes, but did result in the appearance of GFP DNA, and protein in various tissues within the fetuses. Immunohistochemical analysis reveals GFP protein-containing bacteria that appear to be mostly contained within other cells. We were unable to recover any live GFP-expressing bacteria from the fetal tissues. We conclude that S. aureus, and perhaps other bacteria, gain access to the fetus, although it is not clear from these experiments that they survive in the fetus. It is possible that these low inocula and their progeny were effectively cleared by the fetal immune system.
Rate Pressure Product Predicts Cardiovascular Risk in Type 2 Diabetics with Cardiac Autonomic Neuropathy

Background: Unexplained sudden deaths due cardiac involvement are linked to autonomic neuropathy in diabetics but mechanisms remain unclear. Heart rate and pulse pressure etc have been used to predict cardiovascular risk. But the association of Rate Pressure Product remains unascertained. Objective: To predict cardiovascular risk in type 2 diabetic patients with cardiac autonomic neuropathy using a non-invasive indicator, rate pressure product. Materials and Methods: Case control study done on two groups of 20 each, age matched type 2 diabetics with/without cardiac autonomic neuropathy and matched with 20 controls of either sex (n=60). Rate Pressure Product was measured in response to cold pressor and hand grip test. Statistical analysis was done using SPSS software by paired and unpaired t test. Results: There was a significant increase in rate pressure product in controls and in patients without autonomic neuropathy after the tests (p0.001). The change in RPP (ΔRPP) was least in diabetics with autonomic neuropathy and significant in controls and non-neuropathy diabetics using unpaired t-test ( p< 0.05 ). Resting RPP was recorded highest in diabetic autonomic neuropathy patients. Conclusion: Heightened resting RPP and failure of Rate Pressure Product increment during cardiac sympathetic stimulation promotes aggravated ischemic episodes. This renders autonomic neuropathy diabetics vulnerable to adverse cardiovascular events leading to increased morbidity and mortality.
An unusual case of asymmetrical formation and distribution of median nerve

During routine dissection of upper extremity of a 70-year-old male cadaver, variation was found in the formation and distribution of median nerve on both sides. On right side, median nerve received contribution from lateral cord twice, once in the axilla as lateral root of median nerve-1 and again in the arm as lateral root of median nerve-2. Lateral root of median nerve-1 contributed most of its fibers to ulnar nerve. On left side, median nerve had its two roots as usual, lateral root of median nerve and medial root of median nerve. However the lateral root of median nerve crossed the axillary artery anteriorly and formed the median nerve medial to the axillary artery. There was total absence of musculocutaneous nerve on the left side. The muscles of the anterior aspect of the arm, received nerve supply from the median nerve.
Molecular characterization and expression dynamics of MTP genes under various spatio-temporal stages and metal stress conditions in rice

Metal Tolerance Proteins (MTPs) are the class of membrane proteins involved in the transport of metals, mainly Zn, Mn, Fe, Cd, Co and Ni, and confer metal tolerance in plants. In the present study, a comprehensive molecular analysis of rice MTP genes was performed to understand the evolution, distribution and expression dynamics of MTP genes. Exploration of the whole genome re-sequencing information available for three thousand rice genotypes highlighted the evolution and allelic diversity of MTP genes. Based on the presence of non-synonymous single nucleotide polymorphism (SNP), MTP1, MTP6, MTP8 and MTP9 were found to be the most conserved genes. Furthermore, results showed localization of MTP1, MTP8.1 and MTP9, and MTP11, respectively with QTLs/m-QTLs for Zn and Cd accumulation, making these genes promising candidates to understand the QTL regulation. Expression profiling of the entire set of 10 MTP genes revealed root and shoot specific expressions of MTP9 and MTP8.1, respectively, under all tested vegetative stages. Expression of seed-specific MTPs increased as seed maturation progressed, which revealed their potential role in transporting metals during seed filling. Upon exposure to harmful heavy metals, expression of most MTP genes decreased in root and increased in shoot, suggests that different mechanisms are being employed by MTPs in different tissues. Contrastingly, only a few MTPs were found to be responsive to Fe and/or Zn starvation conditions. The extensive analysis of MTPs presented here will be helpful in identifying candidate MTP genes for crop biofortification and bioremediation purposes.
PAX3 is Expressed in the Stromal Compartment of the Developing Kidney and in Wilms Tumors with Myogenic Phenotype

Wilms tumor (WT) is the most frequent renal neoplasm of childhood; a myogenic component is observed in 5% to 10% of tumors. We demonstrate for the first time that myogenic WTs are associated with expression of PAX3, a transcription factor known to specify myoblast cell fate during muscle development. In a panel of 20 WTs, PAX3 was identified in 13 of 13 tumor samples with myogenic histopathology but was absent in 7 of 7 tumors lacking a myogenic component. Furthermore, we show that PAX3 is expressed in the metanephric mesenchyme and stromal compartment of developing mouse kidney. Modulation of endogenous PAX3 expression in human embryonic kidney (HEK293) cells influenced cell migration in in vitro assays. Mutations of WT1 were consistently associated with PAX3 expression in WTs, and modulation of WT1 expression in HEK293 cells was inversely correlated with the level of endogenous PAX3 protein. We demonstrate abundant PAX3 and absence of PAX2 expression in a novel cell line (WitP3) isolated from the stromal portion of a WT bearing a homozygous deletion of the WT1 gene. We hypothesize that PAX3 sets stromal cell fate in developing kidney but is normally suppressed by WT1 during the mesenchyme-to-epithelium transition leading to nephrogenesis. Loss of WT1 permits aberrant PAX3 expression in a subset of WTs with myogenic phenotype.
Impact of particle size, oxidation state and capping agent of different cerium dioxide nanoparticles on the phosphate-induced transformations at different pH and concentration

The potential hazard posed by nanomaterials can be significantly influenced by transformations which these materials undergo during their lifecycle, from manufacturing through to disposal. The transformations may depend on the nanomaterials’ own physicochemical properties as well as the environment they are exposed to. This study focuses on the mechanisms of transformation of cerium oxide nanoparticles (CeO2 NPs) in laboratory experiments which simulate potential scenarios in which the NPs are exposed to phosphate-bearing media. We have experimented with the transformation of four different kinds of CeO2 NPs, in order to investigate the effects of nanoparticle size, capping agent (three were uncapped and one was PVP capped) and oxidation state (two consisted mostly of Ce4+ and two were a mix of Ce3+/Ce4+). They were exposed to a reaction solution containing KH2PO4, citric acid and ascorbic acid at pH values of 2.3, 5.5 and 12.3, and concentrations of 1mM and 5mM. The transformations were followed by UV-vis, zeta potential and XRD measurements, which were taken after 7 and 21 days, and by transmission electron microscopy after 21 days. X-ray photoelectron spectroscopy was measured at 5mM concentration after 21 days for some samples. Results show that for pH 5 and 5mM phosphate concentration, CePO4 NPs were formed. Nanoparticles that were mostly Ce4+ did not dissolve at 1mM reagent concentration, and did not produce CePO4 NPs. When PVP was present as a capping agent it proved to be an extra reducing agent, and CePO4 was found under all conditions used. This is the first paper where the transformation of CeO2 NPs in the presence of phosphate has been studied for particles with different size, shapes and capping agents, in a range of different conditions and using many different characterisation methods.
Consumer-Driven Health Care: The Changing Nature of Health Insurance

Consumer-driven health care (CDHC) plans are a new health insurance paradigm that lets consumers control some of their own health care dollars. It also provides financial incentives to manage medical spending wisely while affording consumers greater choice and control over the types of medical services received. The premise of CDHC is coupling a tax-preferred, personal health account, used to fund day-to-day medical expenses, with a high-deductible health plan to fund care of a catastrophic nature. When individuals enter the medical marketplace, they will spend first from their health savings accounts, health reimbursement arrangements, or flexible spending accounts. Once they reach their deductible, insurance pays all remaining costs. CDHC plans are relatively new to the market, and the market share is still quite small compared to traditional forms of health insurance. CDHC is not for everyone—and not everyone wants to take greater control of health care spending. However, early evidence is encouraging. Virtually all the studies have found that people treat their own money with more care than funds belonging to someone else. Many individuals will appreciate the flexibility in benefits and the added convenience that controlling health care dollars allows.
Diffuse Lung Disease in Infancy: A Proposed Classification Applied to 259 Diagnostic Biopsies

Thoracoscopic and open lung biopsies are being performed with increasing frequency in neonates and infants and are an important component of the diagnostic evaluation of respiratory compromise in these very young children. Diffuse lung disease in infancy includes a wide spectrum of developmental, genetic, inflammatory, infectious, and reactive disorders. The majority of the entities diagnosed in infancy (68%) in this retrospective lung biopsy series are seen almost exclusively in this age group and not in older children and adults. These include primary disorders of pulmonary and pulmonary vascular development, secondary disorders affecting prenatal and/ or postnatal lung growth, genetic disorders of surfactant function, pulmonary interstitial glycogenosis, and neuroendocrine cell hyperplasia of infancy. Although the diagnostic approach to infant lung biopsies is guided primarily by the clinical history and imaging findings, all cases require careful assessment of alveolar growth, vascular architecture, interstitial cellularity, and histologic patterns associated with genetic abnormalities of surfactant metabolism. Recognition of one or more of these processes assists not only in treatment planning but also in further diagnostic evaluation and prognostication and may have implications for subsequent siblings and other family members. In this study, we have applied a classification system developed by a North American multicenter multidisciplinary group to lung biopsies seen at our institution and have used this material to describe and illustrate the spectrum of diffuse lung disease in infancy.
Treatment with direct-acting antivirals improves peripheral insulin sensitivity in non-diabetic, lean chronic hepatitis C patients

Background and aims Hepatitis C virus (HCV) infection is associated with insulin resistance, which may lead to type 2 diabetes and its complications. Although HCV infects mainly hepatocytes, it may impair insulin sensitivity at the level of uninfected extrahepatic tissues (muscles and adipose tissue). The aim of this study was to assess whether an interferon-free, antiviral therapy may improve HCV-associated hepatic vs. peripheral insulin sensitivity. Methods In a single-arm exploratory trial, 17 non-diabetic, lean chronic hepatitis C patients without significant fibrosis were enrolled, and 12 completed the study. Patients were treated with a combination of sofosbuvir/ledipasvir and ribavirin for 12 weeks, and were submitted to a 2-step euglycemic hyperinsulinemic clamp with tracers, together with indirect calorimetry measurement, to measure insulin sensitivity before and after 6 weeks of antivirals. A panel of 27 metabolically active cytokines was analyzed at baseline and after therapy-induced viral suppression. Results Clamp analysis performed in 12 patients who achieved complete viral suppression after 6 weeks of therapy showed a significant improvement of the peripheral insulin sensitivity (13.1% [4.6–36.7], p = 0.003), whereas no difference was observed neither in the endogenous glucose production, in lipolysis suppression nor in substrate oxidation. A distinct subset of hepatokines, potentially involved in liver-to-periphery crosstalk, was modified by the antiviral therapy. Conclusion Pharmacological inhibition of HCV improves peripheral (but not hepatic) insulin sensitivity in non-diabetic, lean individuals with chronic hepatitis C without significant fibrosis.
Dimethyl fumarate dosing in humans increases frataxin expression: A potential therapy for Friedreich’s Ataxia

Friedreich’s Ataxia (FA) is an inherited neurodegenerative disorder resulting from decreased expression of the mitochondrial protein frataxin, for which there is no approved therapy. High throughput screening of clinically used drugs identified Dimethyl fumarate (DMF) as protective in FA patient cells. Here we demonstrate that DMF significantly increases frataxin gene (FXN) expression in FA cell model, FA mouse model and in DMF treated humans. DMF also rescues mitochondrial biogenesis deficiency in FA-patient derived cell model. We further examined the mechanism of DMF's frataxin induction in FA patient cells. It has been shown that transcription-inhibitory R-loops form at GAA expansion mutations, thus decreasing FXN expression. In FA patient cells, we demonstrate that DMF significantly increases transcription initiation. As a potential consequence, we observe significant reduction in both R-loop formation and transcriptional pausing thereby significantly increasing FXN expression. Lastly, DMF dosed Multiple Sclerosis (MS) patients showed significant increase in FXN expression by ~85%. Since inherited deficiency in FXN is the primary cause of FA, and DMF is demonstrated to increase FXN expression in humans, DMF could be considered for Friedreich's therapy.
Avaliação de parâmetros antioxidantes em ratos tratados com sevoflurano

JUSTIFICATIVA Y OBJETIVOS: El sevoflurano es un eter halogenado con fluor que sufre una biotransformacion hepatica a traves del citocromo P450 2E1. Los eteres halogenados que sufren biotransformacion por el P450 2E1, pueden generar especies reactivas del oxigeno (ERO) y promover el debilitamiento del sistema de defensa antioxidante. El objetivo de este trabajo fue investigar la relacion entre la actividad de las enzimas antioxidantes eritrocitarias y el sevoflurano. METODO: Los animales fueron distribuidos en cuatro grupos: Grupo 1 control: apenas oxigeno a 100% (1 L.min-1 por 60 minutos durante 5 dias consecutivos); Grupo 2 - sevoflurano 4,0% en oxigeno a 100% (1 L.min-1 por 60 minutos durante 5 dias consecutivos); Grupo 3 - isoniazida (i.p.), 50 mg.kg-1 de peso corporal /dia, durante 4 dias y enseguida tratados apenas con oxigeno a 100% (1 L.min-1 por 60 minutos durante 5 dias consecutivos); Grupo 4 - isoniazido por via intraperitoneal en dosis de 50 mg.kg-1 de peso corporal, diariamente durante 4 dias, seguido de la administracion del sevoflurano a 4,0% en oxigeno a 100% (1 L.min-1 por 60 minutos durante 5 dias). Despues de 12 horas de la ultima exposicion al sevoflurano, los animales se sacrificaron y la sangre se recolecto a traves de la vena porta para el analisis de la actividad de las enzimas antioxidantes. RESULTADOS: Aumento de la actividad especifica de la glucosa- 6-fosfato deshidrogenasa, reduccion de la actividad especifica de la catalasis, principalmente en el grupo de animales pretratados con isoniazida y enseguida, tratados con sevoflurano. El glutation peroxidasa no presento ninguna alteracion en su actividad. CONCLUSIONES: La interaccion del sevoflurano con inductores enzimaticos del citocromo P450 2E1 puede propiciar la instalacion del estres oxidativo en el caso que la exposicion se prolongue y sea repetitiva.
What is the effect of interrupting prolonged sitting with frequent bouts of physical activity or standing on first or recurrent stroke risk factors? A scoping review

The objective of this review was to ascertain the scope of the available literature on the effects of interrupting prolonged sitting time with frequent bouts of physical activity or standing on stroke and recurrent stroke risk factors. Databases Medline, Embase, AMED, CINAHL and Cochrane library were comprehensively searched from inception until 21st February 2018. Experimental trials which interrupted sitting time with frequent bouts of physical activity or standing in adults (≥ 18 years) were included. Comparison to a bout of prolonged sitting and a measure of at least one first or recurrent stroke risk factor was required to be included. Overall, 30 trials (35 articles) were identified to meet the inclusion criteria. Fifteen trials were completed in participants at an increased risk of having a first stroke and one trial in participants at risk of a recurrent stroke. Outcomes of hypertension and dysglycemia were found to be more favourable following predominately light- to moderate-intensity bouts of physical activity or standing compared to sitting in the majority of trials in participants at risk of having a first stroke. In the one trial of stroke survivors, only outcomes of hypertension were significantly improved. These findings are of significant importance taking into consideration hypertension is the leading risk factor for first and recurrent stroke. However, trials primarily focused on measuring outcomes of dysglycemia and without assessing a dose-response effect. Additional research is required on the dose-response effect of interrupting sitting with frequent bouts of physical activity or standing on first and recurrent stroke risk factors, in those high risk population groups.
Can immigrants counteract employer discrimination? A factorial field experiment reveals the immutability of ethnic hierarchies

How pervasive is labor market discrimination against immigrants and what options do policymakers and migrants have to reduce it? To answer these questions, we conducted a field experiment on employer discrimination in Sweden. Going beyond existing work, we test for a large range of applicant characteristics using a factorial design. We examine whether migrants can affect their employment chances—by adopting citizenship, acquiring work experience, or signaling religious practice—or whether fixed traits such as country of birth or gender are more consequential. We find little systematic evidence that immigrants can do much to reduce discrimination. Rather, ethnic hierarchies are critical: callback rates decline precipitously with the degree of ethno-cultural distance, leaving Iraqis and Somalis, especially if they are male, with much reduced employment chances. These findings highlight that immigrants have few tools at their disposal to escape ethnic penalties and that efforts to reduce discrimination must address employer prejudice.
Targeting DNA-dependent protein kinase sensitizes hepatocellular carcinoma cells to proton beam irradiation through apoptosis induction

Recent studies have highlighted the implications of genetic variations in the relative biological effectiveness (RBE) of proton beam irradiation over conventional X-ray irradiation. Proton beam radiotherapy is a reasonable radiotherapy option for hepatocellular carcinoma (HCC), but the impact of genetic difference on the HCC RBE remains unknown. Here, we determined proton RBE in human HCC cells by exposing them to various doses of either 6-MV X-rays or 230-MeV proton beams. Clonogenic survival assay revealed variable radiosensitivity of human HCC cell lines with survival fraction at 2 Gy ranging from 0.38 to 0.83 and variable proton RBEs with 37% survival fraction ranging from 1.00 to 1.48. HCC cells appeared more sensitive to proton irradiation than X-rays, with more persistent activation of DNA damage repair proteins over time. Depletion of a DNA damage repair gene, DNA-PKcs, by siRNA dramatically increased the sensitivity of HCC cells to proton beams with a decrease in colony survival and an increase in apoptosis. Our findings suggest that there are large variations in proton RBE in HCC cells despite the use of a constant RBE of 1.1 in the clinic and targeting DNA-PKcs in combination with proton beam therapy may be a promising regimen for treating HCC.
The present state of consultation and liaison psychiatry

RICHARD MAYOU, Clinical Reader in Psychiatry, University Department of Psychiatry, Wameford Hospital, Oxford OX3 7JX (correspondence); HELEN ANDERSON, Senior Registrar in Psychiatry, Dykebar Hospital, Paisley, Renfrewshire PA2 7DE; CHARLOTTE FEINMANN, Senior Lecturer, Eastman Dental Hospital, Gray's Inn Road, London WCIX 8LP; GAIL HODGSON, Senior Registrar, Gloucester House, Southmead General Hospital, Bristol BSIO 5NB; and PETER L. JENKINS, Consultant Psychiatrist, St Cadoc's/Royal Gwent Hospital, Caerleon, Newport, Gwent NPI 6XQ
Implementation and Experience of an Alternative QF-PCR and MLPA Diagnostic Strategy to Detect Chromosomal Abnormalities in Fetal and Neonatal Pathology Samples

Chromosomal abnormalities are a significant cause of pregnancy loss. Solid tissue fetal and neonatal pathology samples are routinely examined by karyotype analysis after cell culture. However, there is a high failure rate, and this approach is expensive and labor intensive. We have therefore evaluated a new molecular strategy involving quantitative fluorescent polymerase chain reaction (QF-PCR) and subtelomere multiplex ligation-dependent probe amplification (MLPA) analysis. A retrospective audit showed that less than 4% of abnormal cases may not be detected by this molecular strategy. We validated this strategy in parallel with cytogenetic analysis on 110 patient samples, which included cases of fetal loss, still birth, neonatal death, termination of pregnancy, recurrent miscarriage, and sudden unexpected death in infancy. This validation showed that 55 of the 57 samples that gave a result for both strategies were concordant. During the 1st year of diagnostic testing, we analyzed 382 samples by the molecular strategy. A 16% abnormality rate was observed. These included trisomies 13, 18, 21, monosomy X, and triploidy detected by QF-PCR (77%), and 23% were other trisomies and subtelomere imbalances detected by MLPA. This strategy had a 92% success rate in contrast to the 20%-30% failure rate observed with cell culture and cytogenetic analysis. We conclude that QF-PCR and subtelomere MLPA is a suitable strategy for analysis of the majority of fetal and neonatal pathology samples, with many advantages over conventional cytogenetic analysis.