Determinants of Health and Outcomes in Medicare Recipients With Heart Disease: A Population Study.
Heart disease (HD) is a primary cause of mortality and morbidity in the United States. While there is a growing body of evidence demonstrating the contribution of social determinants of health (SDoH) to HD outcomes, the impact of combined or individual SDoH on health-related quality of life (HRQoL) in patients with HD is not well understood. To analyze the National Health and Aging Trends Study (NHATS) to explore the relationship of SDoH with HRQoL, advance care planning, and treatment preferences in Medicare beneficiaries with HD. The study design was a secondary data analysis using latent class analysis (LCA) and multivariable analysis of NHATS participants with HD, Round 8, that included End of Life Plans and Care questions. 1202 participants, median age 81 years, 57% female, 70% non-Hispanic White, 20% non-Hispanic Black, 10% Other. LCA identified two SDoH risk profiles (low/high), using 12 measures within the NHATS Economic and Social Consequences key concept area. The high-risk SDoH profile participants were more likely to have fair/poor HRQoL, and identify as female, non-White (P < 0.0001); and less likely to have completed advance care planning (P < 0.0001). High-risk SDoH participants were more likely to want life-prolonging treatments (P < 0.0001), however, this association was not significant after adjusting for age, sex, and race (P = 0.344). Higher risk SDoH profiles are associated with reduced HRQoL, reduced advance care planning completion, female sex, and non-White race in a cohort of Medicare beneficiaries. These findings provide opportunities to improve SDoH-related care practices in older patients with HD.


Characteristics of non-insulin-dependent diabetic patients with secondary failure to oral antidiabetic therapy.
Secondary failure to treatment with oral antidiabetic agents frequently occurs in patients with non-insulin-dependent diabetes mellitus. In the search for causes of such failures, we examined patient- and disease-related factors in nonresponders and in responders to treatment with oral antidiabetic agents. The study population consisted of three groups: (1) 34 nonresponders to treatment with sulfonylureas; (2) 25 patients who still responded to treatment with sulfonylureas; and (3) 10 age-matched healthy control subjects. In addition to patient-related factors such as adherence to diet and knowledge of diabetes, we examined insulin response to a test meal and hepatic and peripheral insulin sensitivity during a euglycemic insulin clamp in combination with indirect calorimetry and infusion of [3H-3-]glucose. Patient-related factors such as daily nutrient intake, activity score, knowledge of diabetes, and "stress level" were similar in both groups. However, nonresponders had a higher rate of basal hepatic glucose production (4.60 +/- 0.14 versus 3.63 +/- 0.26 mg/minute/kg of lean body weight; p less than 0.001), which was less suppressed by euglycemic hyperinsulinemia (about 100 microU/mL) than was that of the responders (p less than 0.001). In addition, total insulin-stimulated glucose metabolism was reduced (5.07 +/- 0.22 versus 7.09 +/- 0.56 mg/kg.LBM.minute; p less than 0.001), and this was mainly accounted for by a reduction in non-oxidative glucose metabolism (glycogen synthesis and anaerobic glycolysis) (1.78 +/- 0.22 versus 3.54 +/- 0.49 mg/kg.LBM.minute; p less than 0.001). The severity of hepatic and peripheral insulin resistance correlated with the plasma glucose concentration but was unrelated to insulin secretion. In a multiple linear regression analysis, glucose overproduction in the liver (26.1%), impaired peripheral glucose metabolism (17.3%), and insulin deficiency (12.6%) could explain only 56% of the causes of secondary drug failure. Secondary failure to treatment with oral hypoglycemic agents is determined by the disease itself rather than by patient-related factors. Treatment of secondary drug failure should therefore aim at ameliorating both hepatic and peripheral insulin resistance.


An Initially Missed Diagnosis of Venous Thromboembolic Phenomenon in Adult-Onset Still's Disease: A Case Report and Literature Review.
BACKGROUND Still's disease is a rare multisystemic autoinflammatory disorder. The diagnosis of adult-onset Still's disease (AoSD) can be challenging due to the rarity and overlapping features with many other systemic disorders. Complications of the illness can involve many systems in the human body. One of the least documented hematological complications of AoSD is thromboembolic phenomena. CASE REPORT This text outlines the presentation of a 43-year-old woman with a known diagnosis of AoSD, whose disease-modifying anti-rheumatic drugs (DMARDs) had been tapered and stopped due to remission. She presented with respiratory symptoms and features of an AoSD flare. Lack of complete improvement on antibiotic therapy and reinitiating of DMARDs prompted seeking an alternative/concurrent diagnosis. The work-up yielded a pulmonary embolism (PE) on the background of having no other risk factors for thrombosis. CONCLUSIONS In the reviewed literature, there is a close association between hyperferritinemia and AoSD complicated with venous thromboemboli (VTEs). A rigorous search for alternative diagnoses as well as other potential uncommon complications of AoSD is needed when working-up patients with AoSD, especially those that are not getting better on therapy. Given the rarity of AoSD, meticulous data collection may be useful in understanding the pathophysiology and features of presentation of the illness, including complications such as VTEs.


Clinical outcomes for primary molars treated by different types of pulpotomy: A retrospective cohort study.
Pulpotomy is the amputation of coronally infected pulp tissue to maintain the vitality and function of the radicular pulp. This study was designed to assess the clinical and radiographic success rates of primary molars treated by pulpotomy using diode laser, sodium hypochlorite, or no medication after a follow-up period of 24 months. A retrospective study was conducted by evaluating the success rates of primary molars treated by pulpotomy with diode laser, sodium hypochlorite, or no medication according to the clinical symptoms and signs and radiographic features. There were 145 primary molars included in the study. No significant differences in clinical and radiographic success rates were found among primary molars treated by pulpotomy using diode laser, sodium hypochlorite, or no medication, when the teeth were treated by experienced pedodontists and restored with stainless steel crowns. The 2-year clinical success rates for primary molars treated by pulpotomy using diode laser, sodium hypochlorite, or no medication were all 100%. The 2-year radiographic success rates were 90.9%, 100%, and 87.5% for primary molars treated by pulpotomy using diode laser, sodium hypochlorite, or no medication, respectively. However, when the pulpotomy for primary molars was performed by less-experienced residents, a reduced overall success rate from 94% for attending doctors to 58% for residents was found. Operators and final restorations are confounding factors for determining the success rate of primary molars treated by pulpotomy. Pulpotomy with diode laser, sodium hypochlorite, or no medication are all acceptable treatments of choice for coronally infected primary molars.


In Your Capable Hands: Ethical Practice, Bias Mitigation, and Care for Children Who Rely on Chronic Mechanical Ventilation.
Nurses encounter constraints, pressures and complexity in patient care which may increase reliance on implicit bias -- unconscious, mental shortcuts which shape attitudes and behavior (Kahneman, 2011). These cognitive shortcuts save time, but if unexamined, can undermine the ethical commitment to "respect…the inherent dignity, worth, unique attributes, and human rights of all individuals," (ANA Code, 2015, p.1). This is especially concerning when considering vulnerable populations, such as families with children who are dependent on tracheostomy and mechanical ventilation (trach-vent-dependent). Studies of parent caregivers of children who are trach-vent-dependent raise questions of whether implicit bias contributes to the stigmatization these families experience. Practical strategies to activate the Code of Ethics with Interpretive Statements can mitigate the risks of stigmatization and vulnerability, resulting in improved shared decision making and care for these patients and families. An objective tool to guide patient- and family-centered inquiry and care can anchor nurses' ethical practice.


Ion-exchange chromatographic assay of peptidases acting on the C-terminal hexapeptide sequence of substance P.
A rapid and sensitive assay for peptidases acting on the C-terminal hexapeptide sequence of the neuropeptide substance P is described. The radiolabelled substrate, N alpha-[125I]desaminotyrosyl-substance P (6-11) is easily prepared by coupling commercially available radioiodinated Bolton-Hunter reagent with substance P (6-11). Peptidase activity is determined by quantitative separation of the degradation products from the intact substrate on small QAE-Sephadex columns. The assay has been used to measure degradation of the substrate by rat parotid and diencephalon slices. The peptidase activity in the latter system was inhibited by substance P and substance P fragments and was sensitive to metal chelators and thiol reagents.


A detailed association analysis between the tryptophan hydroxylase 2 (TPH2) gene and autism spectrum disorders in a Japanese population.
We conducted a detailed association analysis between the tryptophan hydroxylase 2 gene and autism spectrum disorders in a Japanese population using 19 markers, including tagging single nucleotide polymorphisms and a novel missense variation, p.R225Q, identified through exon resequencing. However, we failed to obtain supportive evidence for an association.


Non-operative removal of retained stones in the common bile duct.
A method of removal of retained common bile duct stones under radiological control is described and its use in 16 patients reported. The ease of the method, the minimal associated morbidity and the inexpensiveness of the equipment suggest that this should be the primary method of removal of retained stones when a T tube has been placed into the common bile duct.


Quantitative comparison of resting-state functional connectivity derived from fNIRS and fMRI: a simultaneous recording study.
The feasibility of functional near-infrared spectroscopy (fNIRS) to assess resting-state functional connectivity (RSFC) has already been demonstrated. However the validity of fNIRS-based RSFC has rarely been studied. In the present study, fNIRS and fMRI data were simultaneously acquired from 21 subjects during the resting state. After the spatial correspondence was established between the two imaging modalities by transforming the fMRI data into fNIRS measurements space, the index of Between-Modality-Similarity (BMS) of RSFC was evaluated across multiple spatial scales. First, the RSFC between the bilateral primary motor ROI was quite similar between fNIRS and fMRI for all the subjects (BMS(ROI) = 0.95 ± 0.04 for HbO and BMS(ROI) = 0.86 ± 0.13 for HbR). Second, group-level sensorimotor RSFC maps (0.79 for HbO and 0.74 for HbR) showed higher between-modality similarity than individual-level RSFC maps (0.48 ± 0.16 for HbO and 0.41 ± 0.15 for HbR). Finally, for the first time, we combined fNIRS and graph theory to investigate topological properties of resting-state brain networks. The clustering coefficient (C(p)) and characteristic path length (L(p)) which are the most important network topological parameters, both showed high between-modality similarities (BMS(Cp) = 0.90 ± 0.03 for HbO and 0.90 ± 0.06 for HbR; BMS(Lp) = 0.92 ± 0.04 for HbO and 0.91 ± 0.05 for HbR). In summary, the converged results across all the spatial scales demonstrated that fNIRS is capable of providing comparable RSFC measures to fMRI, and thus provide direct evidence for the validity of the optical brain connectivity and the optical brain network approaches to functional brain integration during resting state.


The importance of appropriate prophylaxis for the prevention of venous thromboembolism in at-risk medical patients.
Venous thromboembolism (VTE), which encompasses both deep-vein thrombosis and pulmonary embolism, is a significant healthcare problem, leading to considerable morbidity, mortality and resource utilisation. This review discusses the adherence to VTE guideline recommendations and the available clinical evidence on the appropriate type, dose and duration of VTE prophylaxis. A literature survey was conducted using Pub Med and EMBASE to identify publications related to appropriate thromboprophylaxis in medically ill patients at risk of VTE. Despite evidence from clinical trials and national guidelines, VTE prophylaxis in medically ill patients remains underutilised. The use of unfractionated heparin three-times-daily, low-molecular-weight heparin once-daily and fondaparinux once-daily has demonstrated effectiveness in clinical trials of medically ill patients. However, controversy exists about the use of unfractionated heparin twice-daily, and fondaparinux has not yet received US Food and Drug Administration approval for VTE prophylaxis in medically ill patients. It is important for clinicians to have an understanding of the evidence-based literature when selecting an appropriate drug, at the appropriate dose, for the appropriate duration for VTE prophylaxis in medically ill patients. VTE prophylaxis in medically ill patients is cost-effective, and drugs that are expensive may still be cost-effective when considering improved efficacy and/or safety. Recently, the underutilisation of VTE prophylaxis has led to the involvement of government and other regulatory agencies in an attempt to increase appropriate VTE prophylaxis in US hospitals and improve the clinical and economic outcomes in medical patients at risk of VTE.


The ghost of Saddam and UN sanctions.
Events in the past 10-15 years have meant that Iraq's once highly sophisticated health-care system has fallen to rack and ruin. To fight the very low morale, Iraqi people are making use of many approaches, some of which are unconventional, such as circus entertainment to raise spirits in paediatric wards. This Reportage looks at the events that have lead to the current health-care crisis in Iraq through the eyes of those living and working there. It is based on interviews done by Jo Wilding, an independent humanitarian activist and writer working on various grassroots rehabilitation and solidarity projects in Iraq, in Al Mansour teaching hospital, Shahid Adnan hospital, the centre for Nuclear Medicine, and the Ministry of Health in Baghdad.


Chronological study of ultrastructural changes in the peripheral nerves in Marek's disease.
A chronological study was made of the ultrastructural changes in peripheral nerves following inoculation of 1-day-old chicks with a neurogenic strain of Marek Disease virus. No virus particles were found in nerves. Cellular infiltration of nerves was detected as early as 5 days after inoculation and by 3 weeks some nerves contained proliferative lesions which possessed many of the ultrastructural features characteristic of normal, reactive lymphoid tissue. About 4 weeks after inoculation, coinciding with the onset of neurological signs, areas of widespread demyelination appeared within these lesions; lymphocytes and macrophages penetrated and destroyed the myelin sheath, but spared Schwann cells and most axons. Later oedematous, sparsely infiltrated B type lesions were observed, some of which contained demyelinated nerve fibres undergoing repair; these were therefore a stage in the regression of the proliferative lesions. Our observations do not favour the hypothesis that cellular infiltration of nerves in Marek's disease is the direct result of auto-sensitization to normal myelin. They are consistent with the hypothesis that demyelination is a secondary feature and that the primary lesions are preferential sites for immune demyelination.


Orientia tsutsugamushi in eschars from scrub typhus patients.
To verify the value of eschars for the diagnosis of scrub typhus and to characterize genotypes of Orientia tsutsugamushi in patients, we examined eschars and blood specimens of 7 patients from Shandong Province, People's Republic of China, for O. tsutsugamushi by polymerase chain reaction targeting the Sta56 gene. All 7 eschars and acute-phase blood samples were positive, while no specific DNA amplicons were obtained from the 7 convalescent-phase blood samples collected after antimicrobial drug therapy. The findings indicate that patients' eschars can be used for detection and genetic characterization of O. tsutsugamushi during the convalescent phase.


Synergistic effects of hypertension and aging on cognitive function and hippocampal expression of genes involved in β-amyloid generation and Alzheimer's disease.
Strong epidemiological and experimental evidence indicate that hypertension in the elderly predisposes to the development of Alzheimer's disease (AD), but the underlying mechanisms remain elusive. The present study was designed to characterize the additive/synergistic effects of hypertension and aging on the expression of genes involved in β-amyloid generation and AD in the hippocampus, an area of brain contributing to higher cognitive function, which is significantly affected by AD both in humans and in mouse models of the disease. To achieve that goal, we induced hypertension in young (3 mo) and aged (24 mo) C57BL/6 mice by chronic (4 wk) infusion of angiotensin II and assessed changes in hippocampal mRNA expression of genes involved in amyloid precursor protein (APP)-dependent signaling, APP cleavage, Aβ processing and Aβ-degradation, synaptic function, dysregulation of microtubule-associated τ protein, and apolipoprotein-E signaling. Aged hypertensive mice exhibited spatial memory impairments in the Y-maze and impaired performance in the novel object recognition assay. Surprisingly, hypertension in aging did not increase the expression of APP, β- and γ-secretases, or genes involved in tauopathy. These genes are all involved in the early onset form of AD. Yet, hypertension in aging was associated with changes in hippocampal expression of APP binding proteins, e.g., [Mint3/amyloid β A4 precursor protein-binding family A member 3 (APBA3), Fe65/amyloid β A4 precursor protein-binding family B member 1 (APBB1)], amyloid β (A4) precursor-like protein 1 (APLP1), muscarinic M1 receptor, and serum amyloid P component, all of which may have a role in the pathogenesis of late-onset AD. The hippocampal gene expression signature observed in aged hypertensive mice in the present study provides important clues for subsequent studies to elucidate the mechanisms by which hypertension may contribute to the pathogenesis and clinical manifestation of AD.


Cyclosporine A enhances renin secretion and production in isolated juxtaglomerular cells.
Stimulation of the renin-angiotensin system is a major side effect of the fungoid immunosuppressant cyclosporine A (CyA). The aim of this study was to find out whether or not this effect of CyA results from a direct interaction with renal juxtaglomerular (JG) cells, which are the site of renal renin synthesis and release. Using primary cell cultures from rat renal cortex containing more than 80% JG cells, we found that CyA (0.01 to 10 micrograms/ml) stimulated renin secretion threefold. This stimulation was paralleled by a dose-dependent twofold increase of inactive renin within the cells, while the active intracellular renin remained the same. In order to identify a possible second messenger which could mediate the effects of CyA on JG cells, we examined the simultaneous effects of a single concentration of CyA (1 microgram/ml) on renin secretion, prostaglandin formation and intracellular cAMP concentration. However, prostaglandin formation and cAMP were not detectably altered by CyA in experiments where renin secretion was significantly enhanced. Our results indicate that cyclosporine A stimulates renin secretion and renin synthesis by a direct effect on renal juxtaglomerular cells. This action of CyA is not mediated by changes in cellular prostaglandin or intracellular cAMP.


Cardiovascular autonomic function and vibration perception threshold in type 2 diabetes mellitus.
The aim of this study was to compare cardiovascular autonomic function tests (AFT) and vibration perception threshold (VPT) of patients with type 2 diabetes mellitus (T2DM) with controls. The study was conducted on 60 diabetic patients comparing with 30 controls. The cardiovascular AFT and VPT were assessed in both groups. Among cardiovascular AFT, E:I ratio [1.24 (1.2-1.32) vs 1.3 (1.24-1.4), p=0.001], and Valsalva ratio [1.28 (1.22-1.4) vs 1.6 (1.5-1.73), p=0.001], the indicators of parasympathetic reactivity were reduced in T2DM. Rise in DBP during handgrip, an indicator of sympathetic reactivity was lower in T2DM [12 (10-14) vs 16 (14-18) mmHg, p=0.001] whereas, fall in SBP during head up tilt [4 (4-8) vs 5 (4-8) mmHg] was comparable. VPT (somatic sensation) was comparable between T2DM and control. Autonomic involvement is more marked than somatic, and parasympathetic involvement is more marked than the sympathetic, possibly reflecting severity and chronological pattern of their involvement.


Unraveling the complexities of beryllium contamination in agricultural soils: The case of Qingcheng District, Qingyuan City.
Metal contamination in agricultural soils has received widespread attention; however, the status of beryllium (Be) contamination in agricultural soils has been inadequately studied. This research was conducted to determine the enrichment level and major sources of Be contamination in the agricultural soil in Qingcheng District, Qingyuan City, and to quantify the potential ecological risk and human health risk (PER and HHR) of Be by integrating geological mineral and remote-sensing image maps. The results of principal component analysis followed by multiple linear regression (PCA-MLR) suggest that Be, Sn, Zn, Pb, As, and Cd are mainly derived from anthropogenic activities; V, Ti, Sc, Cr, and Co are mainly derived from medium acidic granites; Al and Si are mainly derived from geological sources; and K and Na are mainly derived from calcium-alkaline materials. Anthropogenic activities are priority material sources owing to the highest contribution. Be contamination poses a slight PER, and the PER level of agricultural soil was moderate. The HHR caused by Be is negligible. The results of this study can serve as the basis for promoting agricultural soil protection and developing and implementing agricultural policies to reduce environmental pollution in the study area.


The permeability coefficient of albumin of the isolated rat mesentery. Modification by some mediators of inflammation, cyclic AMP and calcium.
In order to study the mechanisms whereby mediators of inflammation exert their exudative effects, we used isolated rat mesentery placed as a separation membrane between the two compartments of a diffusion cell. In this experimental arrangement, the permeability coefficient of albumin (PA) can be easily computed from the equilibration rate of 125I-labelled albumin added to one compartment. Histamine, bradykinin, serotonin and prostaglandins A1, A2, E1, E2, F1 alpha and F2 alpha all increased PA to some extent, the maximal values being approx. +60%. Dibutyryl-cyclic AMP, theophylline and isoproterenol also increased PA, thus suggesting involvement of cyclic AMP. Direct measurements of this nucleotide confirmed this hypothesis; furthermore, a linear relation between cyclic AMP levels and PA could be demonstrated. In contrast, cyclic GMP is probably not involved in the control of PA. Calcium-depleted tissues had a low PA (approx. 40% below controls), and did not respond to exogenous prostaglandin E1. These results suggest that transmesenteric passage of albumin is at least partly controlled by cyclic AMP and intracellular Ca2+ levels.


Nociceptive Sensory Fibers Drive Interleukin-23 Production from CD301b+ Dermal Dendritic Cells and Drive Protective Cutaneous Immunity.
Innate resistance to Candida albicans in mucosal tissues requires the production of interleukin-17A (IL-17A) by tissue-resident cells early during infection, but the mechanism of cytokine production has not been precisely defined. In the skin, we found that dermal γδ T cells were the dominant source of IL-17A during C. albicans infection and were required for pathogen resistance. Induction of IL-17A from dermal γδ T cells and resistance to C. albicans required IL-23 production from CD301b(+) dermal dendritic cells (dDCs). In addition, we found that sensory neurons were directly activated by C. albicans. Ablation of sensory neurons increased susceptibility to C. albicans infection, which could be rescued by exogenous addition of the neuropeptide CGRP. These data define a model in which nociceptive pathways in the skin drive production of IL-23 by CD301b(+) dDCs resulting in IL-17A production from γδ T cells and resistance to cutaneous candidiasis.


Hemorrhage Risk Profiles among Different Antithrombotic Regimens: Evidence from a Real-World Analysis of Postmarketing Surveillance Data.
Although the use of direct oral anticoagulants (DOACs) has been reported in patients with atrial fibrillation (AF), there is currently no consensus on the occurrence or characteristics of the hemorrhage risk in different antithrombotic regimens. Disproportionality and Bayesian analyses were performed in mining data of suspected hemorrhagic events after antithrombotic drug use from the FDA Adverse Event Reporting System (FAERS) from January 2004 to September 2019. The time to onset and fatality rate of hemorrhage following different antithrombotic regimens were also compared. A total of 84,998 reports of hemorrhage-related adverse events with the use of antithrombotic drugs were identified. The patients included were mostly from the Americas (80.87%) and Europe (13.22%), with most data submitted by nonhealthcare professionals. Among the seven antithrombotic drug monotherapies, betrixaban had the highest association with hemorrhage based on the highest reporting odds ratio (ROR, 829.95; 95% CI = 113.61-6063.15), proportional reporting ratio (PRR, 24.68, χ2 = 804.24), and multi-item gamma Poisson shrinker (MGPS, 24.68, 95% one-sided CI = 4.67). The combination therapies of clopidogrel plus new oral anticoagulants had higher RORs, PRRs, and empirical Bayesian geometric means (EBGMs) than the antithrombotic drug monotherapies. Hemorrhage associated with rivaroxaban plus clopidogrel appeared to have an earlier onset (171 days vs 219 days, 95% two-sided CI =68.68-27.34, p < 0.0001) and a lower fatality rate (15.30% vs 17.74%, p<0.05) than that associated with rivaroxaban monotherapy. This study provides a relevant overview of the hemorrhagic complications/fatalities associated with different antithrombotic regimens in their real-world use. Among the combination therapies, clopidogrel plus DOACs were found to have stronger associations with hemorrhage than traditional dual antithrombotic therapies. Rivaroxaban showed a stronger association with hemorrhage than other antithrombotic drug monotherapies, and apixaban monotherapy appeared to have weaker associations with hemorrhage than others.


Structure and complete nucleotide sequence of the gene encoding rat fibroblast tropomyosin 4.
We have isolated and determined the complete nucleotide sequence of the gene that encodes the 248 amino acid residue fibroblast tropomyosin, TM-4. The TM-4 sequence is encoded by eight exons, which span approximately 16,000 bases. The position of the intron-exon splice junctions relative to the final transcript are identical to those present in other vertebrate tropomyosin genes and the Drosophila melanogaster TMII gene. We have found no evidence that the rat TM-4 gene is alternatively spliced, unlike all the other tropomyosin genes from multicellular organisms that have been described. Typical vertebrate tropomyosin genes contain some, or all, of alternatively spliced exons 1a and 1b, 2a and 2b, 6a and 6b, and 9a, 9b, 9c and 9d in addition to common exons 3, 4, 5, 7 and 8. The rat fibroblast TM-4 mRNA is encoded by sequences most similar to exons 1b, 3, 4, 5, 6b, 7, 8 and 9d. Two exon-like sequences that are highly similar to alternatively spliced exons 2b and 9a of the rat beta-tropomyosin gene and the human TMnm gene have been located in the appropriate region of the gene encoding rat fibroblast TM-4. However, several mutations in these sequences render them non-functional as tropomyosin coding exons. We have termed these exon-like sequences, vestigial exons. The evolutionary relationship of the rat TM-4 gene relative to other vertebrate tropomyosin genes is discussed.


The effect of laser epilation on recurrence and satisfaction in patients with sacrococcygeal pilonidal disease: a prospective randomized controlled trial.
The primary aim of this prospective study was to investigate the effects of laser epilation on patient satisfaction and recurrence in patients who underwent pilonidal sinus surgery. Sixty patients scheduled for pilonidal sinus surgery in our clinic between 2011 and 2012 were enrolled in this prospective randomized controlled study. Patients were divided in two groups of 30 patients each. Only the Karydakis flap reconstruction technique was performed in the first group. Two sessions of laser epilation were applied in the second group in addition to Karydakis flap reconstruction. The patients in the second group underwent laser epilation 2 weeks before and 3 weeks after the surgery for a total of 2 times in a private office. There were no statistically significant differences between the groups in terms of age, gender, smoking usage, ASA Score, duration of patient's complaints, BMI and hospital stay. There were no statistically significant differences between the groups in terms of surgical site infection, wound separation, abscess formation at the any time postoperatively. There were statistically significant differences between the two groups in the first week post operation considering the VAS pain score (P<0.03) and VAS satisfaction score (P<0.01). While there were statistically significant differences between the two groups in the first month post operation considering the VAS pain score (P<0.0001), there were no statistically significant differences between the groups in terms of VAS satisfaction score in the first and three month postoperatively. In the telephone interviews done 1 year after the surgery, recurrence were detected in 4% of first group and in 20% of second group. Recurrence rates were significantly higher in the second group (P=0.045). Our results show that laser epilation does not reduce the relapse rates in pilonidal sinus surgery, as expected. It is obvious that prospective randomized studies need to be held on this subject.


Spectrum of chronic kidney disease in China: A national study based on hospitalized patients from 2010 to 2015.
To investigate the spectrum of chronic kidney disease (CKD) in China. We used a large national in-patient database covering 878 class three hospitals and involving 64.7 million adult patients in China from 2010 to 2015. The class 3 hospital in China is ranked as the top tier of medical system in China with at least 500 beds and the accreditation from health authorities. The specific causes of CKD were extracted from the International Classification of Diseases-10 codes of discharge diagnoses. A total of 4.5% of hospitalized patients (1.8 million) were identified as CKD, with an increased percentage from 2010 (3.7%) to 2015 (4.7%). Increasing trends of diabetic kidney disease and hypertensive nephropathy were observed from 2010 to 2015 (19.5% vs 24.3% and 11.5% vs 15.9%, respectively), especially for urban residents from north China. The proportion of obstructive nephropathy also increased gradually (10.3% in 2010 vs 15.6% in 2015) and constituted another important cause of CKD for patients, especially for those from south China and rural residents. The spectrum of CKD is changing in China, with variations over time and geographic regions, which has implication regarding developing the prevention strategy of CKD.


The gyrB gene product functions in both initiation and chain polymerization of Escherichia coli chromosome replication: suppression of the initiation deficiency in gyrB-ts mutants by a class of rpoB mutations.
A class of rpoB mutations is described which suppresses replication and transcription deficiency in gyrB-ts mutants shifted to a nonpermissive temperature. The compensatory effect of an altered subunit B of RNA polymerase (rpoB) for the gyrB defect, indicates that transcription is a primary target of the B subunit of DNA gyrase. One gyrB mutation (gyrB402-ts) shows deficiency in chromosome elongation at the nonpermissive temperature, both in vivo and in cells permeabilized with toluene. It is therefore concluded that the gyrB polypeptide functions at least dually in replication; first, at the level of transcription initiation and second, at the level of chain polymerization.


Inverse correlation between combined mutagenicity in Salmonella typhimurium and strength of coordinate bond in mixtures of cobalt(II) chloride and 4-substituted pyridines.
Cobalt(II) chloride (CoCl2), non-mutagenic by itself, has been tested for mutagenic activity in the presence of 4-substituted pyridines in the test strains of Salmonella typhimurium. CoCl2 was found to be mutagenic in strains TA1537 and TA2637, when combined pyridine, with methyl isonicotinate, 4-methyl-pyridine, 4-ethylpyridine, 4-chloropyridine or 4-bromopyridine. Mixtures of CoCl2 and isonicotinic acid, 4-cyanopyridine, 4-aminopyridine, or 4-dimethylaminopyridine exhibited no mutagenicity. Judging from the spectral observations, such combined mutagenicity may be due to the formation of moderate to weak complexes between these compounds and the Co(II) cation.


Penile Length and Testicular Volume in Newborns.
To measure Penile length (PL) and Testicular volume (TV) in newborn boys for assessing genital abnormalities. In a tertiary care setting, measurements of PL and TV were recorded from 480 babies born on alternate days except the weekend, at 24 to 72 h of life by one investigator with the same set of instruments. The penis was stretched to the point of increased resistance and the distance from the tip of the glans penis to the pubic ramus was measured as the stretched PL. Testicular volume was measured by a Prader orchidometer. Improvised beads made of plasticine were used for recording volumes <1 ml. In the study cohort, 365 (76.04 %) were term babies. The mean PL was 34 ± 4.7 mm for the whole cohort while the corresponding value for mean TV was 0.6 ± 0.2 ml. The gestation age-wise percentile charts of PL and TV have been generated. There was modest positive correlation between PL and TV. Positive correlation was also observed between PL and TV and birth weight, body length, and head, chest and arm circumference. Both PL and TV showed statistically significant increase with gestational age. By the index data, the cut-off for suspecting abnormal penile length should be <24.5 or >45.5 mm for term babies. The normative values generated can serve as reference standard in the diagnosis of penile length abnormalities in Indian babies and in clarifying issues of ambiguous genitalia and maldevelopment of male external genitalia.


Microwave-initiated rapid synthesis of phthalated cashew gum for drug delivery systems.
Chemical modification of polysaccharides is an important approach for their transformation into customized matrices that suit different applications. Microwave irradiation (MW) has been used to catalyze chemical reactions. This study developed a method of MW-initiated synthesis for the production of phthalated cashew gum (Phat-CG). The structural characteristics and physicochemical properties of the modified biopolymers were investigated by FTIR, GPC, 1H NMR, relaxometry, elemental analysis, thermal analysis, XRD, degree of substitution, and solubility. Phat-CG was used as a matrix for drug delivery systems using benznidazole (BNZ) as a model drug. BNZ is used in the pharmacotherapy of Chagas disease. The nanoparticles were characterized by size, PDI, zeta potential, AFM, and in vitro release. The nanoparticles had a size of 288.8 nm, PDI of 0.27, and zeta potential of -31.8 mV. The results showed that Phat-CG has interesting and promising properties as a new alternative for improving the treatment of Chagas disease.


Edible seaweed as future functional food: Identification of α-glucosidase inhibitors by combined use of high-resolution α-glucosidase inhibition profiling and HPLC-HRMS-SPE-NMR.
Crude chloroform, ethanol and acetone extracts of nineteen seaweed species were screened for their antioxidant and α-glucosidase inhibitory activity. Samples showing more than 60% α-glucosidase inhibitory activity, at a concentration of 1 mg/ml, were furthermore investigated using high-resolution α-glucosidase inhibition profiling combined with high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy (HR-bioassay/HPLC-HRMS-SPE-NMR). The results showed Ascophyllum nodosum and Fucus vesicolosus to be rich in antioxidants, equaling a Trolox equivalent antioxidant capacity of 135 and 108 mM Troloxmg(-1) extract, respectively. HR-bioassay/HPLC-HRMS-SPE-NMR showed the α-glucosidase inhibitory activity of A. nodosum, F. vesoculosus, Laminaria digitata, Laminaria japonica and Undaria pinnatifida to be caused by phlorotannins as well as fatty acids - with oleic acid, linoleic acid and eicosapentaenoic acid being the most potent with IC50 values of 0.069, 0.075 and 0.10 mM, respectively, and showing a mixed-type inhibition mode.


Expression of Stem Cell Factor in Feline Mast Cell Tumour.
Stem cell factor (SCF) is a ligand of the molecule Kit, which is expressed in mast cells and is important for mast cell proliferation, migration and survival. Mast cell tumours (MCTs) are associated with mutations of c-kit, a proto-oncogene encoding the Kit protein. In this study, we examined SCF expression in 23 samples of feline MCTs. SCF expression was detected in 10 cutaneous MCTs and a case of splenic mastocytosis. In the cutaneous MCTs, SCF-positive tumour cells were located at the margins. Kit was expressed in eight of the 10 cutaneous cases of SCF-expressing MCTs. In these cases, Kit-positive cells were located near to SCF-positive cells, and SCF/Kit double-positive tumour cells were found. Ki67-positive tumour cells were not found near to SCF-positive cells. These results suggest that SCF autocrine/paracrine mechanisms are involved in the expansion of cutaneous MCTs, but not in tumour proliferation.


Large Multinucleated Variant Endothelial Cells in Allograft Kidney Microvasculature: A Biopsy Series.
There are few published studies examining cytomorphologic alterations in endothelial cells in human tissue. One fascinating but largely unexplored endothelial morphologic variant is large multinucleated variant endothelial cells (MVECs). To our knowledge, there are no published reports of MVECs identified in the kidney. Here, we present a case series of 4 kidney biopsies from allograft kidneys whose microvasculature contained MVECs. Electron microscopy confirmed the endothelial identity in all cases. A broad immunohistochemical panel used in 1 case was also confirmatory of an endothelial cell origin. All cases occurred in the setting of chronic, active, antibody-mediated rejection, and alternative etiologies, such as viral infections, were excluded. Two patients were positive for concurrent donor-specific antibodies, and 3 of the 4 cases occurred in second kidney allografts. We speculate that MVECs are a rare or often overlooked finding often confused for megakaryocytes and may be associated with chronic endothelial cell injury in the setting of chronic antibody-mediated rejection.


A review of injection sclerotherapy--the Cape Town experience.
Sclerotherapy is currently used to treat acute variceal bleeds and also in the long-term management after a variceal bleed. The technical variants and results of sclerotherapy in both settings are reviewed and compared with alternative surgical treatment options. Sclerotherapy has become an accepted therapy for acute variceal bleeding. In Cape Town it is used in combination with the Sengstaken tube. A preliminary analysis of an ongoing trial comparing a rigid scope technique with a fibreoptic scope technique provides support for the use of the rigid scope in acute variceal bleeding. The place of repeated sclerotherapy in long-term management has become controversial. Varices can be eradicated and repeated variceal bleeds markedly reduced, but its role in improving survival requires further clarification.


Human basophil chemotaxis and activation are regulated via the histamine H4 receptor.
IgE-mediated cross-linking of FcεRI results in the release of mediators stored in basophil granules, such as histamine and proteases, and in the de novo synthesis of sulfidoleukotrienes. In this study, we investigated the role of the histamine receptors, in particular that of the histamine H4 receptor (H4R), in modulating human basophil function. The mRNA expression of the histamine receptors was measured by real-time PCR. Migration of basophils was assessed using the modified Boyden chamber technique. The expression levels of CD63 and CD203c on the cell surface and the sulfidoleukotriene release were determined by flow cytometry and ELISA, respectively. We could show that highly purified basophils express the H1R, H2R, and H4R but not the H3R mRNA. Human basophils expressed higher H4R mRNA levels as compared to the expression levels of the H1R (P < 0.01). Histamine and the H4R agonist ST-1006 initiated active migration of basophils (P < 0.001). A significant reduction in FcεRI cross-linking-mediated surface expression of CD63 and CD203c was observed on basophils after pre-incubation with histamine or the specific H4R agonist ST-1006 (P < 0.01). The synthesis and release of sulfidoleukotrienes from basophils after activation with different stimuli, by FcεRI cross-linking or by stimulation with hymenoptera venom allergens, were significantly reduced by histamine or the H4R agonist ST-1006 (P < 0.05-0.001). These data imply that the H4R regulates IgE-dependent processes in human basophils and provides a novel function of the H4R preventing an overwhelming immune reaction by engagement of a negative feedback loop.


Susceptibilities to rimantadine of influenza A/H1N1 and A/H3N2 viruses isolated during the epidemics of 1988 to 1989 and 1989 to 1990.
Clinical isolates of influenza A viruses identified during outbreaks in two winters were tested for their rimantadine susceptibilities by an enzyme-linked immunosorbent assay modified from that described previously by Belshe et al. (R. B. Belshe, B. Burk, F. Newman, R. L. Cerruti, and I. S. Sim, J. Virol. 62:1508-1512, 1988). The infectivity titer and the 50% inhibitory concentration of rimantadine were calculated for each virus. Of 105 influenza virus A isolates tested, 28 influenza A/H1N1 isolates from the 1988 and 1989 outbreak and 77 influenza A/H3N2 isolates from the outbreak in following year, were susceptible to the antiviral action of rimantadine.


Evaluation of humoral immune response in relation to COVID-19 severity over 1 year post-infection: critical cases higher humoral immune response than mild cases.
Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2. We investigated the antibody response against SARS-CoV-2 until 1 year after symptom onset. We collected 314 serum samples from 97 patients with COVID-19. Antibody responses were tested using an indirect immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), and plaque reduction neutralization test (PRNT) to detect specific neutralizing antibodies. The positivity rates for neutralizing antibodies at a 1:10 titer cutoff were 58.1% at 1 week, 97.8% at 4 weeks, and 78% at 1 year after symptom onset (53.8% in asymptomatic patients and 89.3% in symptomatic patients). The IFA and anti-S1 ELISA IgG results significantly correlated with neutralizing antibody titers. Critical/fatal cases showed significantly higher antibody titers than the asymptomatic or mild-to-moderate illness groups. Nonetheless, the median number of days to the seroconversion of neutralizing antibodies was 10 and 15 in asymptomatic and symptomatic patients, respectively. The asymptomatic group had a significantly higher neutralizing potency index than the mild-to-severe illness groups. Neutralizing antibodies corresponded to earlier seroconversion but had a shorter presence in the asymptomatic group than in the symptomatic group and were still present 1 year after symptom onset in critical/fatal cases.


The surgeon and his tools-the case for a focused orthopaedic theatre induction programme.
Induction programme for trainee doctors in the UK generally do not focus on the surgical aspects of their jobs. In this context we decided to conduct a telephonic survey among the hospitals belonging to three orthopaedic training regions in the UK from the point of view of the diversity of instrumentations and implants used for index procedures. We chose four index trauma & orthopaedic procedures (Total hip replacement, total knee replacement, intramedullary nailing and external fixator systems for long bone fractures). A telephonic survey was done in six NHS trust hospitals which were part of an orthopaedic training rotation (2 from England, 2 from Wales and 2 from Scotland). In total there were 39 different instrumentation systems for these 4 index procedures in the 6 trusts (see table 1). These comprise 12 Total hip replacement (THR) systems, 14 total knee replacement (TKR) systems, 9 intra-medullary nailing systems, and 4 external fixator systems. The number of different systems for each trust ranged from 7 to 19. There is a vast array of implants and instrumentation systems in each trust, as highlighted by our survey. The surgical tools are not the same in each hospitals. This situation is more complicated when trainees move to new hospitals as part of training rotations. In view of this we feel that more focused theatre based induction programmes for higher surgical trainees is advocated in each hospital trust so trainees can familiarise themselves with the tools available to them. This could include discussion with the consultants and senior theatre staff along with representatives from the companies supplying the implants and instrumentation systems.


Hemodynamics and cutaneous microcirculation during induction of general anesthesia with and without esketamine.
Currently, there are limited data on the effect of macrocirculatory hemodynamic changes on human microcirculation, especially during the induction of general anesthesia (GA). We performed a non-randomized observational trial on patients receiving GA for elective surgery. In the control group (CG), for GA induction sufentanil, propofol, and rocuronium was administered. Patients assigned to the esketamine group (EG) received additional esketamine for GA induction. Invasive blood pressure (IBP) and pulse contour cardiac output (CO) measurement were performed continuously. Microcirculation was assessed using cutaneous Laser Doppler Flowmetry (forehead and sternum LDF), peripheral and central Capillary Refill Time (pCRT, cCRT), as well as brachial temperature gradient (Tskin-diff) at baseline, 5, 10 and 15 minutes after induction of GA. 42 patients were included in the analysis (CG n = 22, EG n = 20). pCRT, cCRT, Tskin-diff, forehead and sternum LDF decreased following GA induction in both groups. IBP and CO were significantly more stable in esketamine group. However, the changes in the microcirculatory parameters were not significantly different between the groups. The addition of esketamine for GA induction warranted better hemodynamic stability for the first five minutes, but had no significant effect on any of the cutaneous microcirculatory parameters measured.


Variations in cardiac activity following acute exposure to copper in three co-occurring but differently zoned Mediterranean limpets.
The cardiac activity of three limpets (Patella rustica, P. caerulea and P. aspera), having a different vertical zonation on the Mediterranean rocky shores, was monitored using a non-invasive technique, during 6 h exposure to copper solutions (0.1 and 0.5 ppm), and after return to copper-free conditions. At 0.1 ppm no significant variation of heart rate was observed in the three species with respect to control conditions, while after 3 h at 0.5 ppm a consistent bradycardia was evident in P. caerulea and P. aspera, but not in P. rustica. After 6 h at 0.5 ppm most of the specimens of the three species were acardic but still reactive to mechanical stimulation. Tests on the resumption of cardiac activity after 6 h exposure to 0.5 ppm showed that even after a prolonged cessation of cardiac activity, limpets quickly resumed heartbeating once returned to clean seawater. However, recovery of heart-beating was faster in the mid- and high-shore species (P. caerulea and P. rustica, respectively) than in the lower-shore P. aspera. Moreover, the cardiac pattern upon recovery was definitely bradycardic in P. aspera, while the other two species showed a significant overshooting in heartbeating rate. Measurement of body burdens of copper showed that P. rustica and P. caerulea were faster in removing the excess of copper than the lower-shore P. aspera. In conclusion, this study showed that taxonomically close and syntopic species having a different zonal distribution exhibit different cardiac responses to water-borne copper and stresses the importance of comparative studies on physiological responses of organisms to metal pollution.


Association between different risk factors and vascular accelerated ageing (EVA study): study protocol for a cross-sectional, descriptive observational study.
The process of population ageing that is occurring in developed societies represents a major challenge for the health system. The aim of this study is to analyse factors that have an influence on early vascular ageing (EVA), estimated by carotid-femoral pulse wave velocity (cf-PWV) and Cardio Ankle Vascular Index (CAVI), and to determine differences by gender in a Spanish population. An observational, descriptive, cross-sectional study. From the population assigned to the participating healthcare centres, a cluster random sampling stratified by age and gender will be performed to obtain 500 participants aged between 35 and 75. Those who meet the inclusion criteria and give written informed consent will be included in the study. Main dependent variables: cf-PWV determined using the SphygmoCor System and CAVI estimated using VASERA. Secondary dependent variables: telomere length, carotid intima-media thickness, central and peripheral augmentation index, ankle-brachial pulse wave velocity, ankle-brachial index, retinal arteriovenous index, and renal and cardiac organ damage. lifestyles (physical activity, adherence to the Mediterranean diet, alcohol and tobacco consumption); psychological factors (depression, anxiety and chronic stress); inflammatory factors and oxidative stress. The study has been approved by the clinical research ethics committee of the healthcare area of Salamanca. All study participants will sign an informed consent form agreeing to participate in the study in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow the understanding of the relationship of the different influencing factors and their relative weight in the development of EVA. At least 5 publications in first-quartile scientific journals are planned. NCT02623894; Pre-results.


TAL effectors mediate high-efficiency transposition of the piggyBac transposon in silkworm Bombyx mori L.
The piggyBac (PB) transposon is one of the most useful transposable elements, and has been successfully used for genetic manipulation in more than a dozen species. However, the efficiency of PB-mediated transposition is still insufficient for many purposes. Here, we present a strategy to enhance transposition efficiency using a fusion of transcription activator-like effector (TALE) and the PB transposase (PBase). The results demonstrate that the TALE-PBase fusion protein which is engineered in this study can produce a significantly improved stable transposition efficiency of up to 63.9%, which is at least 7 times higher than the current transposition efficiency in silkworm. Moreover, the average number of transgene-positive individuals increased up to 5.7-fold, with each positive brood containing an average of 18.1 transgenic silkworms. Finally, we demonstrate that TALE-PBase fusion-mediated PB transposition presents a new insertional preference compared with original insertional preference. This method shows a great potential and value for insertional therapy of many genetic diseases. In conclusion, this new and powerful transposition technology will efficiently promote genetic manipulation studies in both invertebrates and vertebrates.


Detection and mechanism of formation of the potent direct-acting mutagen 2-bromoacrolein from 1,2-dibromo-3-chloropropane.
The nematocide 1,2-dibromo-3-chloropropane (DBCP) was converted to products which are mutagenic for Salmonella typhimurium TA 100 in the presence of rat liver microsomes, NADPH, and oxygen. Typical in vivo and in vitro inhibitors of cytochrome P-450 decreased DBCP mutagenicity in the presence of microsomes. Addition of glutathione to cytosolic preparations failed to bioactivate DBCP to mutagenic metabolites. Mutagenicity studies with selectively deuterated analogs showed that substitution of deuterium for hydrogen at C-1 or C-3 of DBCP modestly decreased mutagenicity, but that deuteration at both C-1 and C-3 markedly decreased mutagenicity. The formation rates of the potent direct-acting mutagen, 2-bromoacrolein (2-BA), in incubations of DBCP and its deuterated analogs with rat liver microsomes, correlated with the isotope effects on mutagenicity. Characterization of 2-BA was accomplished by gas chromatography-mass spectrometry using positive-ion chemical ionization. Mass spectral analysis of 2-BA formed from specifically deuterated analogs of DBCP indicated that initial oxidative dehalogenation at C-1 followed by a spontaneous beta-elimination reaction was the preferred pathway in the formation of 2-BA from DBCP. These results demonstrate that mutagenic metabolites of DBCP are formed by cytochrome P-450-mediated oxidative metabolism, and that 2-BA is a major mutagen formed.


Role of cardiac chloride currents in changes in action potential characteristics and arrhythmias.
Various types of Cl- currents have been recorded in cardiac myocytes from different regions of the heart and in different species. With few exceptions, most of these currents are not active under basal conditions, but are activated under the influence of various agonists and by physical stress. These channels are distributed nonuniformly, depending on the cell type, tissue and region of the heart. Therefore, Cl- current activation may influence membrane potential and impulse formation differently in different cells, and may play a role in arrhythmogenesis. Among these Cl- currents, the protein kinase A-activated Cl- current (I Cl.PKA), the stretch- or swelling-activated Cl- current (I Cl.SWELL) and the Ca(2+)-activated Cl current (I Cl.Ca) comprise the major anion currents that modify cardiac electrical activity. These currents exhibit outward-going rectification, or are predominantly activated at depolarized voltages and, thus, contribute significantly to shortening of the action potential duration but little to diastolic depolarization. The action potential shortening by Cl- current activation may not only perpetuate reentry by shortening the refractory period in a reentry pathway, but may also prevent the development of early afterdepolarization and triggered activity caused by the prolongation of action potentials. I Cl.Ca contributes to delayed afterdepolarization at diastolic potentials in Ca(2+)-overloaded cells. Another factor limiting the influence of Cl- currents on diastolic potentials is the presence of a predominantly opposing background K+ current, except at the nodal regions that lack these K+ channels, or under conditions of decreased K+ conductance. Therefore, the contribution of Cl- currents to the genesis of arrhythmias may depend on their association with the conductance of other ions, especially that of K+.


Arbovirus Surveillance and First Report of Chikungunya Virus in Wild Populations of Aedes aegypti from Guerrero, Mexico.
We carried out dengue (DENV) and chikungunya virus (CHIKV) surveillance in wild populations of Aedes aegypti from Guerrero, Mexico, from 2012 to 2014 following a standard national protocol of the Mexican Dengue Control Program. A total of 284 pools (15-30 specimens/pool) of female mosquitoes were tested with real-time reverse transcriptase-polymerase chain reaction to detect DENV and CHIKV. We report for the 1st time the detection of CHIKV from field-collected mosquitoes at Acapulco and Juchitán in 2014. Results from DENV are also reported.


DNA polymorphisms of the apolipoprotein B gene are associated with obesity and serum lipids in healthy Indians in Singapore.
Three DNA polymorphisms (Ins/Del, XbaI and EcoRI) of the apolipoprotein B gene and their influence on body-mass index, serum lipids and apolipoprotein levels were studied in 181 healthy Indians of both sexes (121 males and 60 females), aged between 17 and 71 years. The frequencies of X+ (XbaI) and Del (Ins/Del) of the signal peptide region in Indians were found to be significantly lower (0.17 and 0.11, respectively) compared to the frequencies in Caucasians (0.50 and 0.32, respectively) (P < 0.025). The frequency of E- (EcoRI) was similar to that in Caucasians (0.10 vs 0.15). A highly significant linkage disequilibrium was observed between the XbaI site and Ins/Del polymorphism of the apo B gene in this sample (X2 = 31.9, P < 0.001). The simultaneous presence of Del and X+ allele was significantly associated with higher body mass index (X2 = 11.43, P < 0.005), serum total cholesterol (X2 = 5.11; P < 0.025) and triglyceride (X2 = 6.42; P < 0.025) levels. Mean values of adjusted BMI and serum triglyceride levels were found to be 29.0 +/- 1.92 vs 23.7 +/- 0.67 (P < 0.025) and 278.0 +/- 60.78 vs 140.4 +/- 15.43 mg/dl (P < 0.05), respectively, in subjects with Del and X+ compared to others. The multiple regression tests showed that 3.3 and 5.8% of the total variability of BMI is explained by Ins/Del and XbaI polymorphism, respectively, in this sample (P = 0.06 and 0.02), while 3.8% of serum triglyceride levels was explained by Ins/Del polymorphism of the apo B gene (P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)


Immunohistological localization of the myelinating cell-specific receptor LP(A1).
LP(A1) (also termed Edg-2 or VZG-1) is a G-protein-coupled receptor for lysophosphatidic acid and its gene transcripts have been found selectively expressed by mature myelin-producing cells. We have raised in rabbit a polyclonal antibody against a sequence unique to LP(A1) and common to rat, mouse, and human orthologues. In Western blots, LP(A1) immunoreactivity appeared as 44-53 kDa bands in extracts from recombinant RH7777 cells expressing LP(A1), mouse purified oligodendrocytes, or human white matter, but not from wild-type RH7777 cells or purified astrocytes. In glial cultures, LP(A1) immunoreactivity was restricted to oligodendrocytes, appeared at cell membrane and processes, colocalized with myelin basic protein, and appeared before myelin/oligodendrocyte glycoprotein. In slices of rat and human brains, LP(A1) immunoreactivity was found in myelinated tracts, as well as in oligodendrocyte somata and their myelinating fibers. Immunoreactivities of LP(A1) and myelin basic protein colocalized in the brain, but oligodendrocyte soma showed stronger signals for LP(A1) than myelinated fibers, whereas the reverse was true for myelin basic protein. These results strengthen the view that LP(A1) is involved in myelin formation or maintenance.


Sex identification by male-specific growth hormone pseudogene (GH-psi) in Oncorhynchus masou complex and a related hybrid.
It is often difficult to identify sexes of many fish species by conventional cytological method because of the lack of heteromorphic sex chromosomes. Isolation of sex-specific molecular markers is thus important for sexing and for understanding sex chromosome evolution in these species. We have identified genetic sexes by PCR-based male-specificity of a growth hormone pseudogene (GH-psi) in masu and Biwa salmon, two subspecies of the Oncorhynchus masou complex, and their hybrid Honmasu. PCRs with primers designed from sequences of chinook salmon GH genes amplified GH-I and GH-II fragments in both sexes, but a third GH-psi fragment was detected in predominant proportion of males and very few phenotypic females. The consistency of phenotypic sex with genetic sex identified by GH-psi for masu salmon, Biwa salmon and Honmasu was 93.1, 96.7 and 94%, respectively. The remaining individuals showed inconsistency or deviation from sex-specificity: a few phenotypic males lacked the GH-psi, whereas a few phenotypic females possessed the GH-psi. Sequence of the putative GH-psi fragment from such females was identical to that from genetic males, and shared about 95% homology with the corresponding GH-psi fragment from chinook salmon. This result confirmed that these females were really GH-psi-bearing individuals. PCR analyses with primers designed from masu salmon GH-psi gave identical results, indicating that the absence of GH-psi in a few males was not resulted from primer mismatching. These GH-psi-bearing females and GH-psi-absent males were more likely to originate from spontaneous sex reversion than from crossing-over between GH-psi and the sex determination gene/region.


Self-catalyzed inactivation of cytochrome P-450 during microsomal metabolism of cannabidiol.
When cannabidiol (CBD) was incubated with hepatic microsomes of mice in the presence of an NADPH-generating system, a significant decrease of cytochrome P-450 content was observed by measuring its carbon monoxide difference spectra. The decrease of cytochrome P-450 by CBD required NADPH and molecular oxygen. The effect was partially inhibited by SKF 525-A but not by various scavengers of active oxygen species, superoxide anion, hydroxyl radical and singlet oxygen. The incubation of CBD with hepatic microsomes did not affect total heme but decreased significantly free sulfhydryl contents in the microsomes. The derivatives of CBD modified in the resorcinol moiety, CBD-monomethyl- and dimethylethers, almost lost the effect on cytochrome P-450, whereas those modified in the terpene moiety, 8,9-dihydro- and 1,2,8,9-tetrahydro-CBDs exhibited some potency to inactivate cytochrome P-450. The inactivation of cytochrome P-450 by CBD and related compounds led to the inhibition of hepatic microsomal p-nitroanisole O-demethylase and aniline hydroxylase activities. These results suggest that the resorcinol moiety of CBD plays some role in the inactivation of cytochrome P-450 by the cannabinoid.


Primary Sjögren's syndrome presenting as autonomic neuropathy. Case report.
Abnormalities of the autonomic nervous system have been described in several connective tissue diseases, but the relation with primary Sjögren's syndrome is unclear. This report describes a patient with primary Sjögren's syndrome who presented with severe autonomic failure. The present knowledge on dysfunction of the autonomic nervous system in primary Sjögren's syndrome and other connective tissue diseases is shortly reviewed.


Interleukin-25 induces type 2 cytokine production in a steroid-resistant interleukin-17RB+ myeloid population that exacerbates asthmatic pathology.
Interleukin-25 (IL-25) is a cytokine associated with allergy and asthma that functions to promote type 2 immune responses at mucosal epithelial surfaces and serves to protect against helminth parasitic infections in the intestinal tract. This study identifies the IL-25 receptor, IL-17RB, as a key mediator of both innate and adaptive pulmonary type 2 immune responses. Allergen exposure upregulated IL-25 and induced type 2 cytokine production in a previously undescribed granulocytic population, termed type 2 myeloid (T2M) cells. Il17rb(-/-) mice showed reduced lung pathology after chronic allergen exposure and decreased type 2 cytokine production in T2M cells and CD4(+) T lymphocytes. Airway instillation of IL-25 induced IL-4 and IL-13 production in T2M cells, demonstrating their importance in eliciting T cell-independent inflammation. The adoptive transfer of T2M cells reconstituted IL-25-mediated responses in Il17rb(-/-) mice. High-dose dexamethasone treatment did not reduce the IL-25-induced T2M pulmonary response. Finally, a similar IL-4- and IL-13-producing granulocytic population was identified in peripheral blood of human subjects with asthma. These data establish IL-25 and its receptor IL-17RB as targets for innate and adaptive immune responses in chronic allergic airway disease and identify T2M cells as a new steroid-resistant cell population.


Excess winter morbidity among older people at risk of cold homes: a population-based study in a London borough.
Fuel poverty frequently affects older low-income households, in homes that are difficult to heat. Excess winter deaths occurring in Britain are widely attributed to effects of cold. This pilot study examined the demonstrability of a relationship between older people's health and fuel poverty risk, using morbidity data. An observational, population-based study was made of 25,000 residents aged >or=65 years in the London Borough of Newham (LBN). Using Hospital Episode Statistics (HES) data over 1993-1997, anonymized at enumeration district (ED) level, we calculated excess winter morbidity, based on emergency hospital episodes for all respiratory diagnosis codes. EDs were variously aggregated after ranking against a proposed Fuel Poverty Risk Index (FPR), including factors of energy inefficient housing, low income, householder age and under occupation. FPR is a predictor of excess winter morbidity. In particular, FPR was observed showing a significant relationship with high winter morbidity counts for 2 of 4 years studied. Using FPR as a two-level factor (high and non-high), the model provides odds ratios: for 1993, winter/summer morbidity ratio for high FPR is 1.7 higher than the corresponding ratio for non-high FPR [95% confidence interval (CI)=1.1-2.7], and for 1996, the odds ratio is 1.6 (95% CI=0.9-2.8). In a regression with grouped EDs, having allowed for FPR, no other variables in our set contribute to the difference between winter and summer morbidity counts. Results may indicate supporting evidence of a relationship between energy inefficient housing and winter respiratory disease among older people, with public health implications for increasing health-driven energy efficiency housing interventions.


An observational study of the management practices and outcomes of patients with new onset atrial fibrillation in non-cardiothoracic surgeries.
Limited data exist on characteristics and management of patients with postoperative atrial fibrillation (POAF) after noncardiothoracic surgeries and on the relationship between symptoms and outcomes. We sought to describe clinical features, in-hospital practices and outcomes in patients with new POAF by the presence or absence of clinical symptoms. Retrospective cohort study of adults with POAF in one tertiary center. Among the 99 patients who fulfilled the eligibility criteria, median age was 75 years (IQR 64-83) and 57.6% were male. Only thirty percent of patients with POAF were symptomatic. Rate control/conversion to sinus rhythm was achieved in ≤ 4 h in 56% of the patients and in 80% was maintained for ≥ 24 h. Anticoagulation was prescribed in 50% of those discharged in AF; the CHADS2-VASc score was not associated with anticoagulation prescribed. One third of patients were readmitted and half of them were in AF. Asymptomatic patients had lower median heart rate than symptomatic patients but no other clinical characteristics, or outcomes were different. Most patients with POAF were asymptomatic but their presentation or outcomes were similar with symptomatic patients. One in four discharged patients was prescribed anticoagulation and the CHADS2-VASC score was not associated with this decision. These findings have important implications for practice and future research. There is a need to better delineate the risk associated with transient versus persistent POAF, symptomatic versus asymptomatic POAF, as well as for clinical trials to determine optimal strategies to improve their outcomes.


[Importance of HPV status and p16 for the prognosis of penile carcinoma].
Penile cancer is a rare but often lethal tumour disease, especially in the metastatic stage. Most data on prognostic factors for penile cancer are based on small patient cohorts, and even meta-analyses are mostly limited in terms of patient numbers. There is a lack of sufficient parameters to predict the metastatic risk of these tumours. Furthermore, the role of the HPV status for the prognosis, and, in this regard, of p16INK4a is still unclear. In this study, 236 patients from an international multicentre cohort were analysed with regard to histological subtypes, HPV and p16 status, and other clinical parameters. The HPV status was only graded as HPV-positive if HPV was detected by PCR and the p16 status defined by immunochemistry was positive. The statistical analysis was carried out using the Kaplan-Meier method as well as the log-rank test and a univariable and multivariable analysis using the Cox regression model. A positive HPV status was not a significant parameter for either metastasis-free (MFS), tumour-specific (CSS) or overall survival (OS). p16-positive tumours showed a significantly better MFS (p=0.026), which was also confirmed in the subgroup analysis of HPV-negative tumours (p=0.037) without differences in CSS or OS. In the usual type, there was also a trend towards an improved MFS, but without statistical significance (p=0.070). p16-positive tumours were associated with a highly significantly better MFS (hazard ratio 0.3; p=0.004) in the multivariable Cox regression, while patients with a pT1b tumour stage or advanced lymph node metastasis showed a significantly worse survival. In the multivariable analysis of HPV-negative tumours, p16 status was also confirmed as an independent predictor of MFS (Hazard ratio 0.2; p=0.007). HPV status alone seems to be lacking prognostic relevance. In contrast, p16 status was confirmed as an independent prognostic factor. Thus, the expression of p16INK4a is associated with a significantly better MFS. Especially in HPV-negative tumours, the p16 status should be evaluated with regard to the prognostic value and thus also with a view to the treatment decision.


The potential of digestate as a biofertilizer in eroded soils of Lithuania.
The objective of this work was to determine the potential of using of solid and liquid digestate, as biofertilizer and soil amendment, and to address adverse unfertile soil erosion problems after analysing areas of potential use. We found a high concentration of organic carbon in a solid fraction of the digestate, which indicates a significant potential for returning carbon to the soil. The influence of digestate fertilization on soil fertility as a function of the amount of available phosphorus (P2O5) and potassium (K2O) in the 0-40 cm layer was found to be very important. The soil fertility category was changed from "high" (200-300 mg kg-1) to "very high" (>300 mg kg-1) according P2O5, using only 170 kg ha-1 of nitrogen in solid and liquid digestate rate. Fertilization with all phases and rates of digestate tend to increase the amount of K2O. The solid digestate fertilization using the 170 kg ha-1 N rate showed a significant increase (5 times) of mineral nitrogen content in the 0-40 cm soil layer. The advantage of solid digestate as a soil improver has been highlighted because it has a positive effect on soil fertility, quality, sustainability and durability. The amount of mobile humic acids (MHA) in eroded loamy Retisol increased 1.6 times in soil 0-40 cm layer with a fertilization rate of 170 kg ha-1 and 1.5 times - of 85 kg ha-1 of solid digestate compared to the untreated. Similar trends of MHA but in lower amount were identified when liquid digestate was applied.


Improved nutrient use efficiency increases plant growth of rice with the use of IAA-overproducing strains of endophytic Burkholderia cepacia strain RRE25.
Effect of indole acetic acid (IAA)-overproducing mutants of Burkholderia cepacia (RRE25), a member of β-subclass of Proteobacteria and naturally occurring rice endophyte, was observed on the growth of rice (Oryza sativa L.) plants grown under greenhouse conditions. Nine mutants were characterized for altered biosynthesis of IAA after nitrous acid mutagenesis. These mutants were grouped into two classes: class I mutants have reduced production of IAA as compared to the wild type, while class II mutants showed overproduction of IAA. Mutants of both classes and RRE25, the parent (wild type), were inoculated on rice seedlings of two cultivars (Sarjoo-52 and NDR-97). Uptake of nitrogen, phosphorous, and potassium was estimated in these plants. Significant increase in the amount of uptake of all three elements was observed when inoculated with the IAA-overproducing mutants over control as well as in the plants inoculated with the wild type (RRE25). Effect of inoculation of IAA-overproducing mutants was more pronounced on the uptake of phosphorous in cultivar NDR-97 than Sarjoo-52, while it was opposite with respect to potassium uptake. Any significant difference was not observed in nitrogen uptake among the two cultivars. It shows that the host also plays an important role in the beneficial endophytic association. It was concluded from these results that one of the possible mechanisms of growth promotion of rice plants inoculated with bacterial endophytes is their effects on an increase in the capability of nutritional uptake possible through the effect of IAA production which results in proliferation of root system that could mine more nutrients from the soil.


Strangulated bowel obstruction caused by an ileo-ileal knot: a rare case report.
Intestinal knot formation is a condition wherein two segments of the intestine are knotted together; however, reports of small-intestinal ileo-ileal knot formation are rare. The patient was a 62-year-old Asian male with a history of endoscopic colorectal adenoma resection and a spontaneous pneumothorax. The patient had no history of a laparotomy. He consulted his local doctor with the chief complaint of abdominal pain and was admitted to our hospital with suspicion of an acute abdomen. The abdomen had muscular guarding with tenderness and rebound tenderness. Contrast-enhanced computed tomography (CT) showed torsion of the mesentery of the small intestine with poor contrast filling. The patient was referred to our department with strangulated bowel obstruction and underwent an emergency laparotomy. Intraoperative findings revealed that two segments of the ileum were wrapped around each other to form a knot, and the strangulated small bowel was necrotic. After the release of the knot, partial resection of the small intestine was performed from 220 cm distal to the ligament of Treitz to 80 cm proximal to the cecum. The patient had a good postoperative course and was discharged on the 11th postoperative day. Ileo-ileal knots should be considered as part of the differential diagnosis when treating strangulated bowel obstruction.


Comparison of quality of life in end-stage renal disease patients undergoing hemodialysis and peritoneal dialysis in a Moroccan city.
End-stage renal disease patients (ESRD) generally complain about a poor quality of life (QOL). The current study aims to describe and compare ESRD patients' QOL according to dialysis modalities (hemodialysis [HD] and peritoneal dialysis [PD]). This is a cross-sectional study, conducted in dialysis facilities of a Moroccan university hospital, during October 2018. All adult ESRD patients, treated either by HD or PD for more than 3 months and agreeing to participate, were included. Medical data were collected using a questionnaire, whereas the QOL data were collected using the Kidney Disease Quality of Life Short Form (KDQOL SF v 1.3) scale previously validated in dialectal Arabic. The patients' characteristics and QOL data were compared between dialysis modalities (HD vs. PD), using a linear regression, before and after adjustment on several demographic and medical factors as well as a propensity score created to reduce the effect of confounding factors related to the choice of the treatment. Out of the 91 included patients (50.5% of men, median age 52.0 (IQR [36.5; 62.0]) years), 71 were on HD and 20 were on PD. The highest subscale score, for all participants, was the social support's one with a median of 83.3 (IQR [66.7; 100]), and the lowest one was the kidney disease burden with a median of 25.0 (IQR [0.00; 46.9]). The univariate analysis showed that the Physical Component Score (PCS), the cognitive function, and the dialysis staff encouragement were better in PD patients (p = 0.03, p = 0.04, and p = 0.007, respectively), while the multiple linear regression indicates that the PCS, the dialysis Staff encouragement, and the patient's satisfaction subscores decreased within patients on HD compared with those on PD (p = 0.01, p = 0.03, and p = 0.02, respectively) and that the burden of the kidney disease and the work status subscores increased within patients on HD against those on PD (p = 0.007 and p = 0.04, respectively). This study showed a significant difference between dialysis modalities in some sides of quality of life.


Stimulation of the nucleus paraventricularis thalami suppresses scratching and biting behaviour of arthritic rats and exerts a powerful effect on tests for acute pain.
In 20 arthritis-sensitive Wistar rats, an electrode was implanted in the paraventricular thalamic nucleus (PV). In the tail-flick and hot-plate test, PV was stimulated continuously for a period of 30 min, during which every 5 min either a tail-flick or hot-plate test was performed. Stimulation of PV induced important prolongations of the reaction times on tail-flick and hot-plate tests. However, there was no significant correlation between the results of the two tests. The effect of stimulation was immediate and did not outlast the stimulation period. PV stimulation did not give rise to tolerance, either within the stimulation period of 30 min, or during the successive testing days. After the termination of these acute pain tests, rats were inoculated with Mycobacterium butyricum. All animals developed polyarthritis. PV stimulation had a profound suppressive effect on the scratching and biting behaviour displayed by the animals. This reduction in scratching and biting behaviour was specific for PV stimulation since stimulation of another target, the ventrolateral thalamic nucleus (4 animals), had no effect on these behaviours. The attenuation of the scratching and biting behaviour was not a result of a general motor impairment, since other behaviours increased (running and sniffing) or did not change. There was no significant correlation between the results of scratching behaviour with those of the tail-flick and hot-plate test.


Does nutritional education improve the risk factors for cardiovascular diseases among elderly patients with type 2 diabetes? A randomized controlled trial based on an educational model.
To evaluate the effects of a nutritional education program on cardiovascular risk among elderly patients with type 2 diabetes (T2D). Ninety-seven elderly patients with T2D were enrolled in the present randomized controlled educational trial study. Patients were divided into intervention and control groups. The belief, attitude, subjective norm, enabling factors (BASNEF) educational model was used to design the educational intervention. Patients in the control group received their usual care during the study. Anthropometric data, lipid profiles and blood pressure measurements were collected at baseline and Week 12 in each group. Significant declines were observed in the intervention compared with control group in terms of body weight (-1.3 ± 1.1 vs. 0.11 ± 0.58 kg, respectively), body mass index (-0.48 ± 0.37 vs. 0.05 ± 0.22 kg/m2, respectively), serum triglyceride levels (-18.25 ± 32.15 vs. -3.67 ± 22.61 mg/dL, respectively; P < 0.05 for all), and the waist-to-hip ratio (P = 0.03). There were no significant differences between the intervention and control groups in terms of high-density lipoprotein-cholesterol (-1.02 ± 4.35 vs. -1.10 ± 6.93 mg/dL, respectively; P = 0.9) or low-density lipoprotein-cholesterol (-4.04 ± 11.64 vs. -1.08 ± 4.35 mg/dL, respectively; P = 0.2). Short-term nutritional education based on the BASNEF educational model improves serum triglyceride levels and anthropometric indices in elderly patients with T2D.


Hsa_circ_0008934 promotes the proliferation and migration of osteosarcoma cells by targeting miR-145-5p to enhance E2F3 expression.
To investigate the role of hsa_circ_0008934 in osteosarcoma and the molecular mechanism involved in the regulation of the occurrence and development of osteosarcoma METHODS: Differentially expressed circRNAs in the osteosarcoma cell lines SaOS2 and MG63 and in the normal human osteoblast cell line hFOB1.19 were identified via next-generation RNA sequencing. The expression and circular morphology of hsa_circ_0008934 were analyzed via quantitative real-time polymerase chain reaction (qRT-PCR) and RT-PCR analysis, respectively. Proliferation, apoptosis, cell cycle progression, migration, and invasion of SaOS2 and MG63 cells with hsa_circ_0008934 silencing or overexpression were assessed using the MTS method, colony formation assay, flow cytometry, and the transwell system, respectively. The subcellular distribution of hsa_circ_0008934 was revealed via fluorescence in situ hybridization. The binding of hsa_circ_0008934 with microRNAs was confirmed using the dual-luciferase reporter assay. The oncogenic roles of hsa_circ_0008934 in osteosarcoma were determined using an in vivo tumorigenesis assay with nude mice. qRT-PCR, western blotting, TUNEL assay, and immunohistochemistry (IHC) were used to detect the tumorigenicity of hsa_circ_0008934 in osteosarcoma cells. Many circRNAs were differentially expressed in SaOS2 and MG63 cells than in hFOB1.19 cells. Hsa_circ_0008934 expression was significantly elevated in SaOS2 and MG63 cells. Hsa_circ_0008934 silencing significantly reduced proliferation, enhanced apoptosis, blocked cell cycle progression, and impaired migration and invasion capacities of SaOS2 cells. Opposite cellular alterations were achieved by overexpressing hsa_circ_0008934 in MG63 cells. Hsa_circ_0008934 was mainly distributed in the cytosol and positively regulated E2F3 expression in osteosarcoma cells. In addition, it directly bound with miR-145-5p to repress E2F3 expression and enhanced the tumorigenesis of MG63 cells in nude mice. qRT-PCR revealed that the intracellular injection of hsa_circ_0008934 lentivirus resulted in hsa_circ_0008934 overexpression and miR-145-5p downregulation. Western blotting confirmed that E2F3 was upregulated. Moreover, the TUNEL assay showed that hsa_circ_0008934 overexpression inhibited the apoptosis of tumor cells. IHC detection revealed that the hsa_circ_0008934 overexpression could promote the expression of Ki67 and PCNA. Elevated hsa_circ_0008934 expression promotes the proliferation and migration of osteosarcoma cells by sponging miR-145-5p to enhance E2F3 expression.


First-principle investigation of magnetic coupling mechanism in hypothesized a-site-ordered perovskite YMn₃Sc₄O₁₂.
We have systematically investigated the electronic and magnetic properties of hypothesized A-site-ordered perovskite YMn₃Sc₄O₁₂ using first-principle calculation based on the density functional theory. Our calculated results predict that YMn₃Sc₄O₁₂ is both thermodynamically and mechanically stable and its ground state is antiferromagnetic insulator. The Mn(3+) is in the high-spin state. More importantly, by comparison to YMn₃Sc₄O₁₂, we point out that the empty Sc 3d orbital provides the Mn--O--Sc--O--Mn superexchange interaction, which is similar to its isostructural perovskite CaCu₃Ti₄O₁₂, and enhances the antiferromagnetic interaction between Mn ions. From these calculations, we can clearly see that the empty 3d orbital plays an important role to realize superexchange interaction.


A rare postoperative complication after a step-up approach for walled-off pancreatic necrosis: locating a difficult digestive duct fistula.
We present the case of a gallbladder-abscess cavity fistula in a 46-year-old male with walled-off pancreatic necrosis (WOPN). A step-up approach was used for two months, which consisted of a minimally invasive necrosectomy followed by postoperative percutaneous lavages with two drainage tubes. The range of the abscess was significantly reduced, as shown by the computerized tomography scan (Fig. 1). However, a substantial amount of odorless, pale yellow, feculent fluid (almost 1,000 ml daily) was discharged from the drainage tubes over the following days, without lavages.


The Bagenal letters.
In 2006 Mrs John Bagenal made a gift to the British Dental Association archive of part of the correspondence of her late husband John Stuart Bagenal. The 13 letters were written to his family during the spring and summer of 1940, when, having enlisted as a private in Royal Army Medical Corps, he was posted to Colchester for training as a dental clerk-orderly. The letters are an invaluable record of the process by which new units of the Army Dental Corps were staffed by other ranks, and show a young man turning from civilian pleasures to soldierly responsibility.


Friendship trumps neediness: The impact of social relations and others' wealth on preschool children's sharing.
Recent work has suggested the presence of a variety of motives and mechanisms that affect young children's sharing decisions. Yet, little is known about the relative impact of these motives. In three experiments with 3- to 6-year-old children (total N=140), the current study contrasts two important recipient characteristics that have been suggested to play a major role in early sharing; the positive social relationship between children and recipients and the differences in recipients' wealth. To this end, children could allocate resources to a friend who already possessed a lot of them and to a nonfriend (Experiments 1 and 2) or a stranger (Experiment 3) who owned only very few resources. Across age, children showed a preference to share more with their rich friend, although this tendency was stronger in the older preschool children. The findings are discussed with respect to theoretical accounts on the psychological basis of early sharing.


The micro-assay of the disaccharide isomers of chondroitin sulphate.
Connective tissue extracts containing the 4- and 6-sulphated isomers of chondroitin sulphate can be measured at the microgram level (approximately 10 microgram) using colorimetric assays. The chondroitin sulphates are depolymerised to disaccharides using chondroitin ABC lyase (EC 220.127.116.11). The 4- and 6-sulphated disaccharides after treatment with acid periodate are determined using a thiobarbituric acid procedure. An alkaline borate p-dimethylaminobenzaldehyde reaction is used to measure 6-sulphated disaccharide, the 4-sulphated disaccharide not forming a chromogen. Unsulphated disaccharide causes interference in both assays and if present is separated prior to assay using paper electrophoresis fractionation.


Impact of Profound Burn on the Quality of Life of Women Attended at the Referral Outpatient Clinic in the State of Pernambuco.
Analyze the influence of deep-degree burns on the quality of life (QoL) of women at treatment in ambulatory after hospital discharge. A cross-sectional study was conducted at a reference public hospital for burns in Recife, Pernambuco, Brazil, from August 2017 to May 2018. Fifty adult women over 20 years old who suffered deep burns and were in outpatient rehabilitation treatment were included. The variables studied were biological, sociodemographic, and clinical. The dynamometry and goniometry tests and the instruments to verify the QV Burn-Specific Health Scale-Revised were included in the analysis. Multiple linear regression models were fitted to identify factors associated with the six domains of the QoL instrument. The results identified a greater negative influence of burns on the QoL of women when associated with the variables: dark-black skin color, low levels of education, low income, motion impairment in right upper limb and lesions less than 6 months in the face, head and neck region. It should be noticed that the overall QoL score presented a median of 92.0, a score considered high, revealing an important QoL impairment. Deep-degree burn victims had a great impact on physical, emotional, and psychological abilities, acting harmfully on their self-image and causing difficulties in the execution of their daily and professional life activities, which are reinforced by aspects such as social position, level of education, and extent and duration of injury, resulting in a low QoL.


Treatment provision for gambling disorder in Britain: call for an integrated addictions treatment and commissioning model.
Treatment provision for individuals with gambling problems in Britain is at best inadequate. Here we call for gambling treatment provision to be integrated into mainstream drug and alcohol services, and for its commissioning responsibilities to fall under local public health departments.


Evaluating risk factors for re-exploration due to postoperative neck hematoma after thyroid surgery: a nested case-control study.
Postoperative bleeding after thyroid surgery remains a potentially lethal complication. Outpatient thyroidectomy is an increasing trend in the high volume centers. There is a need to identify risk factors for postoperative bleeding in order to select proper patients for outpatient thyroidectomy. This study aimed to investigate this issue using a national population-based register. A nested case-control study on patients registered in the Swedish national register for endocrine surgery (SQRTPA) was performed. Patients with postoperative bleeding were matched 1:1 by age and gender to controls. Additional information on cases and controls was obtained from attending surgeons using a questionnaire. Risk factors for postoperative bleeding were evaluated with logistic regression and are presented as odds ratios (ORs) with 95% confidence intervals (CIs). The time of bleeding in relation to surgery was also investigated. There were 9494 operations, and 174 (1.8%) of them involved postoperative bleeding. In the whole cohort, patients with postoperative bleeding were older, 58 (46-69) vs. 49 (37-62) years, than patients without, p < 0.01. Male patients had a higher risk of bleeding, OR 2.18 (95% CI 1.58-2.99). In the case-control cohort, drain was an independent risk factor for bleeding, OR 1.64 (1.05-2.57). Two-thirds of patients bled within 6 h after surgery. The incidence of bleeding after 24 h was 10%. High age, male gender, and drain are independent risk factors for bleeding after thyroid surgery. Even with careful patient selection, prolonged observation might be necessary in thyroid surgery.


Molecular Basis for the Remarkably Different Gas-Phase Behavior of Deprotonated Thyroid Hormones Triiodothyronine (T3) and Reverse Triiodothyronine (rT3): A Clue for Their Discrimination?
Thyroid hormones are biologically active small molecules responsible for growth and development regulation, basal metabolic rate, and lipid and carbohydrate metabolism. Liquid chromatography mass spectrometry (LC-MS) can be used to quantify thyroid hormones blood level with high speed and selectivity, aiming to improve the diagnosis and treatment of the severe pathological conditions in which they are implicated, i.e., hypo- and hyperthyroidism. In this work, the gas-phase behavior of the isomeric thyroid hormones triiodothyronine (T3) and reverse triiodothyronine (rT3) in their deprotonated form was studied at a molecular level using MS-based techniques. Previously reported collision-induced dissociation experiments yielded distinct spectra despite the high structural similarity of the two compounds, suggesting different charge sites to be responsible. Infrared multiple photon dissociation spectroscopy on [T3-H]- and [rT3-H]- was performed, and the results were interpreted using DFT and MP2 calculations, assessing the prevalence of T3 in the carboxylate form and rT3 as a phenolate isomer. The different deprotonation sites of the two isomers were also found to drive their ion-mobility behavior. In fact, [T3-H]- and [rT3-H]- were successfully separated. Drift times were correlated with collisional cross section values of 209 and 215 Å2 for [T3-H]- and [rT3-H]-, respectively. Calculations suggested the charge site to be the main parameter involved in the different mobilities of the two anions. Finally, bare [T3-H]- and [rT3-H]- were made to react with neutral acetylacetone and trifluoroacetic acid, confirming rT3 to be more acidic than T3 in agreement with the calculated gas-phase acidities of T3 and rT3 equal to 1345 and 1326 kJ mol-1, respectively.


Quantitative trait loci underlying resistance to sudden death syndrome (SDS) in MD96-5722 by 'Spencer' recombinant inbred line population of soybean.
The best way to protect yield loss of soybean [Glycine max (L.) Merr.] due to sudden death syndrome (SDS), caused by Fusarium virguliforme (Aoki, O'Donnel, Homma & Lattanzi), is the development and use of resistant lines. Mapping quantitative trait loci (QTL) linked to SDS help developing resistant soybean germplasm through molecular marker-assisted selection strategy. QTL for SDS presented herein are from a high-density SNP-based genetic linkage map of MD 96-5722 (a.k.a 'Monocacy') by 'Spencer' recombinant inbred line using SoySNP6K Illumina Infinium BeadChip genotyping array. Ninety-four F5:7 lines were evaluated for 2 years (2010 and 2011) at two locations (Carbondale and Valmeyer) in southern Illinois, USA to identify QTL controlling SDS resistance using disease index (DX). Composite interval mapping identified 19 SDS controlling QTL which were mapped on 11 separate linkage group (LG) or chromosomes (Chr) out of 20 LG or Chr of soybean genome. Many of these significant QTL identified in one environment/year were confirmed in another year or environment, which suggests a common genetic effects and modes of the pathogen. These new QTL are useful sources for SDS resistance studies in soybean breeding, complementing previously reported loci.


Imaging Technologies in Spine Surgery.
This article presents a comprehensive review of the evolution of both invasive and noninvasive imaging technologies that are part of the arsenal of spinal diagnostics and surgical therapy. The text provides not only a historical lens to the evolution of the imaging technologies that are part of routine contemporary practice but also provides a detailed sketch of emerging imaging technologies, such as endoscopic and exoscopic systems. Augmented reality, virtual reality, and mixed reality are new technologies that have enhanced the preparation of surgery and provide excellent case-specific training modules to break down each step of an operation in isolation.


Multidimensional Analysis of Protease Substrates and Their Cellular Origins in Mixed Secretomes from Multiple Cell Types.
Although extracellular proteases are confronted with substrate proteins expressed by multiple cell types in vivo, in most protease substrate discovery approaches, the test protease is exposed to a test proteome (secretome) derived only from a single cell type. This limits the potential substrate space and prohibits the formation of protein complexes constituted of components derived from multiple cellular origins. Mixing of secretomes collected from multiple cell types addresses this issue, but information on the cellular origin of a substrate protein is lost. Here, we describe a protocol and the corresponding data analysis workflow for a multidimensional substrate discovery approach termed SILAC -iTRAQ -TAILS that is based on hyperplexed terminal amine isotopic labeling of substrates (TAILS ), allowing identification of substrates and concomitant assignment to cellular origins in mixed secretomes within the same experiment.


Steady states, charge movements, and rates for a cloned GABA transporter expressed in Xenopus oocytes.
Voltage-clamp analysis was applied to study the currents associated with the uptake of extracellular gamma-aminobutyric acid (GABA) by the cloned transporter GAT1 expressed at high efficiency in Xenopus oocytes. Steady-state GABA currents were increased at higher extracellular [GABA], [Na+], and [Cl-] and at more negative potentials. The Hill coefficient for Na+ exceeded unity, suggesting the involvement of two Na+ ions. In the absence of GABA, voltage jumps produced transient currents that behaved like capacitive charge movements; these were suppressed by the uptake inhibitor SKF-89976A, were shifted to more negative potentials at lower external [Na+] and [Cl-], and had an effective valence of 1.1 elementary charge. A turnover rate per transporter of 6-13/s at maximal [GABA] (-80 mV, 96 mM NaCl, 22 degrees C) is given both by the kinetics of voltage jump relaxations and by the ratio between the maximal GABA currents and the charge movements. These quantitative data are necessary for evaluating the roles of GAT1 in synaptic function.