Digital technology for health promotion: opportunities to address excess mortality in persons living with severe mental disorders.
Persons with severe mental disorders (SMDs) experience dramatically reduced life expectancy compared with the general population. We consider the role of digital technologies for addressing this serious public health concern. In this clinical review, we apply the multilevel risk model recently introduced by the WHO to conceptualise how digital technology can support efforts to reduce excess mortality risk at the individual, health system and social determinants of health levels. In particular, digital technologies show promise for targeting preventable physical health conditions in persons with SMDs. However, evidence on the use of these technologies for addressing early mortality risk factors is lacking. At the individual level, digital interventions show promise for managing mental health symptoms, promoting healthy lifestyle behaviours and targeting substance use concerns. At the health system level, digital interventions can support care coordination, clinician training, screening and monitoring health indices and shared decision-making. At the social determinants of health level, digital interventions can facilitate opportunities to engage peers for illness self-management and health promotion and for delivering and/or augmenting supported employment programmes. The time is ripe to capitalise on early evidence to support future development, testing and delivery of effective digital efforts targeting risk factors that contribute to shorter life expectancy in persons with SMDs. Key challenges and opportunities for future research include increasing user engagement, involving users during development and testing of digital interventions, carefully considering risks/harms and rigorously evaluating effectiveness and costs to support the scalability and sustainability of promising digital approaches.


Assessing the impact of climate change on disease emergence in freshwater fish in the United Kingdom.
A risk framework has been developed to examine the influence of climate change on disease emergence in the United Kingdom. The fish immune response and the replication of pathogens are often correlated with water temperature, which manifest as temperature ranges for infection and clinical diseases. These data are reviewed for the major endemic and exotic disease threats to freshwater fish. Increasing water temperatures will shift the balance in favour of either the host or pathogen, changing the frequency and distribution of disease. A number of endemic diseases of salmonids (e.g. enteric red mouth, furunculosis, proliferative kidney disease and white spot) will become more prevalent and difficult to control as water temperatures increase. Outbreaks of koi herpesvirus in carp fisheries are likely to occur over a longer period each summer. Climate change also alters the threat level associated with exotic pathogens. The risk of viral haemorrhagic septicaemia (VHSV), infectious haematopoietic necrosis virus (IHNV) and spring viraemia of carp virus (SVCV) declines as infection generally only establishes when water temperatures are less than 14°C for VHSV and IHNV and 17°C for SCVC. The risk of establishment of other exotic pathogens (epizootic haematopoietic necrosis and epizootic ulcerative syndrome) increases. The spread of Lactococcus garvieae northwards in Europe is likely to continue, and thus is more likely to be both introduced and become established. Measures to reduce the threat of exotic pathogens need to be revised to account for the changing exotic diseases threat. Increasing water temperatures and the negative effects of extreme weather events (e.g. storms) are likely to alter the freshwater environment adversely for both wild and farmed salmonid populations, increasing their susceptibility to disease and the likelihood of disease emergence. For wild populations, surveillance and risk mitigation need to be focused on locations where disease emergence, as a result of climate change, is most likely.


Evaluation of Community-Based Policy, Systems, and Environment Interventions Targeting the Vending Machines.
The American Heart Association conducted policy, systems, and environmental (PSE) focused interventions to increase healthy vending in 8 communities. PSE interventions were assessed using the Nutrition Environment Measures Survey Vending Assessment to see changes in the food environment. Baseline and follow-up assessments were conducted with 3 settings and a total of 19 machines. PSE changes resulted in increased availability of healthy options and decreased unhealthy options. Implementation of PSE interventions targeting the food environment can be an effective method of providing increased access to healthy foods and beverages with the goal of increasing consumption to decrease chronic diseases.


Discrete-time model of an adaptive optics systems.
The standard adaptive optics system can be viewed as a sampled-data feedback system with a continuous-time disturbance (the incident wavefront from the observed object) and discrete-time measurement noise. A common measure of the performance of adaptive optics systems is the time average of the pupil variance of the residual wavefront. This performance can be related to that of a discrete-time system obtained by lifting the incident and residual wavefronts. The corresponding discrete-time model is derived, and the computation of the adaptive optics system residual variance is based on that model. The predicted variance of a single mode of an adaptive optics system is shown to be the same as that obtained via simulation (as expected). The discrete-time prediction is also shown to be superior to a continuous-time approximation of the adaptive optics system.


Rehabilitation of fractures in small animals: maximize outcomes, minimize complications.
Successful fracture management accomplishes 2 major objectives: bony union and return to functional activities. For many years, Physical Therapy has routinely helped human patients recovering from fractures reach their functional goals by helping them regain movement, flexibility, strength, coordination, and balance. Rehabilitation is now commonly provided to small animals recovering from fractures to accomplish similar goals. Knowledge of tissue healing is critical when determining the appropriate stresses to apply throughout the healing timeline. The detrimental effects of immobilization, including the potential for development of fracture disease, must be considered when formulating a Rehabilitation plan of care. Many Rehabilitation interventions are readily amenable to application by both Veterinary professionals and owners of patients. Superficial thermal modalities, passive range of motion and stretching, soft tissue massage, therapeutic ultrasound, electrical stimulation, and therapeutic exercise can ensure a more complete patient recovery. Providing owners with education regarding appropriate patient handling and home modifications allows a safer return to the home environment. Detailed written instructions for rehabilitation at home promotes owner compliance and accurate completion.


[Diagnostic procedures in artificially ventilated patients with pneumonia].
Pneumonia is a common complication in patients requiring mechanical ventilation and the mortality is high. The diagnosis is difficult to establish in spite of many available diagnostic techniques: Aspiration from endotracheal tube or tracheostomy, fiberbronchoscopy with bronchial aspiration, protected specimen-brush (PSB), bronchoalveolar lavage (BAL), transbronchial biopsy or percutaneous lung needle aspiration or open lung biopsy. A review of the literature is given. It is concluded that PSB and BAL combined with quantitative cultures are valid tools, but there is no conclusion as to the superiority of one over the other. With the use of prior antibiotics the rate of false negatives increases and the specificity and sensitivity are lowered. However, we do need a prospective, randomized trial in order to demonstrate that invasive methods in fact decrease morbidity and mortality in the patients compared with clinical judgement alone.


Gastric cancer: Translating novels concepts into clinical practice.
The overall 5-year survival of gastric cancer (GC) has change only little in the last decades and it remains the fifth leading cause of cancer-related death worldwide. However, in the past few years a more effective combination chemotherapy has raised the bar of curability of about 10% in resectable disease. Morever, a deeper knowledge of GC biology have unveiled biomarkers to help personalize adjunctive treatments in patients candidate to surgery. Despite a plateau in efficacy of fist-line treatment, incremental survival advantages have been recorded in unresectable advanced disease. The growing number of effective drugs in second and later lines along with a more judicious delivery of cytotoxics and early supportive interventions have enabled more patients to proceed beyond first-line. The continuum of care has become a reality in a considerable proportion of patients that offer opportunities to improve outcomes. Finally, the advent of the immune checkpoint inhibitors has brought great expectations in molecularly-defined subset of patients. This Review summarizes the state-of-the art in the management of GC together with novel concepts that have entered clinical development with the potential of change practice in the foreseeable future.


Further studies on the role of proteases in the allergic reaction.
Protease activity was measured through the hydrolysis of synthetic amino acid esters in body fluids and tissues of guinea pigs, rats, mice, and humans. Significant in vitro activation was observed in serum and lung slices of sensitized guinea pigs on addition of the specific antigen. Increased proteolytic activity was also seen in reverse anaphylaxis. More marked activation occurred when guinea pig serum was treated with peptone and guinea pig or rat serum was treated with agar. Protease activation was demonstrated in specimens of human skin under the influence of a poison ivy extract or croton oil added in vitro. Urinary protease activity of guinea pigs increased significantly during the first hours of anaphylactic shock and very markedly in peptone shock. Peptone shock, elicited in mice pretreated with H. pertussis, was accompanied by a considerable increase in protease activity in the peritoneal fluid as compared with non-pretreated mice which were insensitive to peptone. Proteolytic activity resulting from the activation procedures was due to a number of proteases. The dominant substrate affinity and inhibition patterns suggest that serum and urine proteases are similar to but not identical with plasmin. Anaphylactic activation exhibited patterns different from those resulting from the action of anaphylactoid agents. Tissue enzymes are either of cathepsin- or chymotrypsin-type or mixtures of both. Some of the activated enzymes, although remarkably effective in hydrolyzing amino acid esters, show no activity on protein substrates. This does not justify, however, their designation as "esterases." They probably belong to the class of specific proteases acting only on a single or a small number of functionally significant protein substrates. There is at present sufficient evidence to prove not only that protease activation does occur in anaphylaxis and anaphylactoid conditions but also that it is an important component of the chain of reactions leading to the allergic response.


An electron microscopic study of the fascia from the medial and lateral sides of clubfoot.
Two cell types were observed in fascia from the lateral side of the clubfoot: a cell resembling the fibroblast of hypertrophic scar and a fibroblast-like cell with dilated rough endoplasmic reticulum. Three cell types were observed in fascia from the medial side of the clubfoot: typical fibroblasts, cells resembling myofibroblasts, and mast cells. The contracture of the medial side may be due to the myofibroblast-like cells, and this contracture may be enhanced by histamine released from the mast cells. The stretching of the lateral side is probably due to a compensatory fibrosis that maintains the tissue density.


Automatic Classification of Anterior Chamber Angle Using Ultrasound Biomicroscopy and Deep Learning.
To develop a software package for automated classification of anterior chamber angle of the eye by using ultrasound biomicroscopy. Ultrasound biomicroscopy images were collected, and the trabecular-iris angle was manually measured and classified into three categories: open angle, narrow angle, and angle closure. Inception v3 was used as the classifying convolutional neural network and the algorithm was trained. With a recall rate of 97% in the test set, the neural network's classification accuracy can reach 97.2% and the overall area under the curve was 0.988. The sensitivity and specificity were 98.04% and 99.09% for the open angle, 96.30% and 98.13% for the narrow angle, and 98.21% and 99.05% for the angle closure categories, respectively. Preliminary results show that an automated classification of the anterior chamber angle achieved satisfying sensitivity and specificity and could be helpful in clinical practice. The present work suggests that the algorithm described here could be useful in the categorizing of anterior chamber angle and screening for subjects who are at high risk of angle closure.


DNA-binding activities of the HilC and HilD virulence regulatory proteins of Salmonella enterica serovar Typhimurium.
The HilC and HilD proteins of Salmonella enterica serovar Typhimurium are members of the AraC/XylS family of transcription regulators. They are encoded on Salmonella pathogenicity island 1 (SPI1) and control expression of the hilA gene, which encodes the major transcriptional activator for many genes encoded on SPI1 and elsewhere that contribute to invasion of host cells. Gel electrophoretic shift and DNase footprinting assays revealed that purified HilC and HilD proteins can bind to multiple regions in the hilA and hilC promoters and to a single region in the hilD promoter. Although both HilC and -D proteins can bind to the same DNA regions, they showed different dependencies on the sequence and lengths of their DNA targets. To identify the binding-sequence specificity of HilC and HilD, a series of single base substitutions changing each position in a DNA fragment corresponding to positions -92 to -52 of the hilC promoter was tested for binding to HilC and HilD in a gel shift DNA-binding assay. This mutational analysis in combination with sequence alignments allowed deduction of consensus sequences for binding of both proteins. The consensus sequences overlap but differ so that HilC can bind to both types of sites but HilD only to one. The hilA and hilC promoters contain multiple binding sites of each type, whereas the hilD promoter contains a site that binds HilC but not HilD without additional binding elements. The HilC and HilD proteins had no major effect on transcription from the hilA or hilD promoters using purified proteins in vitro but changed the choice of promoter at hilC. These results are consistent with a model derived from analysis of lacZ fusions stating that HilC and HilD enhance hilA expression by counteracting a repressing activity.


Impaired neuromuscular transmission of the tibialis anterior in a rodent model of hypertonia.
Early-onset hypertonia is characteristic of developmental neuromotor disorders, including cerebral palsy (CP). The spa transgenic mouse displays early-onset spasticity, abnormal gait, and motor impairments that are remarkably similar to symptoms of human CP. Previously, we showed that spa mice have fewer motor neurons innervating the tibialis anterior (TA). An expanded innervation ratio may result in increased susceptibility to neuromuscular transmission failure (NMTF). We assessed NMTF in an ex vivo TA muscle nerve preparation from spa and wild-type (WT) mice by comparing forces elicited by nerve versus muscle stimulation. TA muscle innervation ratio was assessed by counting the number of muscle fibers and dividing by the number of TA motor neurons. Muscle fiber cross-sectional areas were also assessed in the TA muscle. We observed that NMTF was immediately present in spa mice, increased with repetitive stimulation, and associated with increased innervation ratio. These changes were concomitant with reduced TA muscle fiber cross-sectional area in spa mice compared with WT. Early-onset hypertonia is associated with increased innervation ratio and impaired neuromuscular transmission. These disturbances may exacerbate the underlying gait abnormalities present in individuals with hypertonia.NEW & NOTEWORTHY Nerve-muscle interaction is poorly understood in the context of early-onset spasticity and hypertonia. In an animal model of early-onset spasticity, spa mice, we found a marked impairment of tibialis anterior neuromuscular transmission. This impairment is associated with an increased innervation ratio (mean number of muscle fibers innervated by a single motor neuron). These disturbances may underlie weakness and gait disturbances observed in individual with developmental hypertonia and spasticity.


[Estrogen therapy effect in arterial tension in postmenopausal women].
Experimental studies have shown that estrogens prevent deposit of cholesterol in arteries, have effect upon the endothelial function (to prevent contraction of smooth muscle), and enlarge the vascular tone or vasodilatation. To determine changes in arterial pressure before and after use of estrogen-therapy. A descriptive study was carried out follow-up during 8 weeks in Obstetric and Gynecologic Hospital (No. 3), Instituto Mexicano del Seguro Social. We included 250 postmenopausal women with prescribed estrogen-therapy. Arterial tension was determined before and after therapy; descriptive statistics and student t test (value, p < 0.05) was employed. Menopause was present in a mean of age of 46 +/- 4.2 years (M +/- SD); height was 1.53 +/- 0.6 m; corporal weight, 60.9 +/- 10.2 kg, and hip-waist index was 81.3 +/- 5.4. Mean arterial tension before estrogen-therapy was 90.2 +/- 10.0 mmHg, and after, 85.7 +/- 9.6 mmHg (p < 0.05). There is evidence of estrogen-therapy vasodilatation and hypotension effects, with clinical changes statistically significative; however is recommendable that such estrogenic therapy must be individualized and attended in slender form. Hormonal therapy (estrogens) has benefits in arterial tension of postmenopausal women.


Activation of Sphingolipid Pathway in the Livers of Lipodystrophic Agpat2-/- Mice.
A several fold increase in triacylglycerol is observed in the livers of lipodystrophic Agpat2-/- mice. We have previously reported an unexpected increase in the phosphatidic acid (PA) levels in the livers of these mice and that a few specific molecular species of PA were able to transcriptionally upregulate hepatic gluconeogenesis. In the current study, we measured the metabolites and expression of associated enzymes of the sphingolipid synthesis pathway. The entire sphingolipid pathway was activated both at the gene expression and the metabolite level. The levels of some ceramides were increased by as much as ~eightfold in the livers of Agpat2-/- mice. Furthermore, several molecular species of ceramides were increased in the plasma of Agpat2-/- mice, specifically ceramide C16:0, which was threefold elevated in the plasma of both the sexes. However, the ceramides failed to increase glucose production in mouse primary hepatocytes obtained from wild-type and Agpat2-/- mice, further establishing the specificity of PA in the induction of hepatic gluconeogenesis. This study shows elevated levels of sphingolipids in the steatotic livers of Agpat2-/- mice and increased expression of associated enzymes for the sphingolipid pathway. Therefore, this study and those in the literature suggest that ceramide C16:0 could be used as a biomarker for insulin resistance/type 2 diabetes mellitus.


Cerebrospinal fluid leakage due to nasoseptal flap partial necrosis: A pitfall for skull base reconstruction of endoscopic endonasal surgery.
Vascularized nasoseptal flaps allow for the reconstruction of large dural defects and have remarkably reduced the incidence of postoperative complications during endoscopic endonasal skull base surgery. Nevertheless, some complications related to nasoseptal flap have been reported. Flap necrosis is a rare, but serious issue is associated with meningitis and cerebrospinal fluid (CSF) leak. We performed endoscopic endonasal removal of the tuberculum sella meningioma in a 39-year-old woman with a history of Turner syndrome using abdominal fat, fascia, and a vascularized nasoseptal flap for dural and skull base defect reconstruction. After surgery, she developed CSF leak, and reoperation revealed partial necrosis of the septal flap that caused leakage. At this time, with a concern that removal of the necrotic part may lead to the insufficient size of the flap, we filled the gap tightly with fat pieces. However, the CSF leak recurred, and thus, we performed debridement of the necrotic region and reformed the multilayered reconstruction, following which she no longer experienced CSF leakage. Our case suggested that partial rather than total flap necrosis could occur, possibly due to variances of vascular anatomy, leading to focal ischemia. Debridement of the necrotic region may be an important solution for recurrent cerebrospinal leakage secondary to partial necrosis of a nasoseptal flap.


Active Duty Service Members, Primary Managers, and Administrators' Perspectives on a Novel Sleep Telehealth Management Platform in the U.S. Military Healthcare System.
Sleep disorders are common in the military, and there is a gross shortage of sleep specialists in the military health system. The purposes of the present study were to (1) understand perceptions and expectations surrounding sleep telehealth approaches and (2) solicit feedback to optimize and refine a proposed novel sleep telehealth management platform. To accomplish these objectives, we investigated the perceptions, expectations, and preferences of active duty service members (ADSMs) with sleep disorders, primary care managers (PCMs), and administrative stakeholders regarding sleep telehealth management. Using convenience sampling, we conducted five focus groups with 26 ADSMs and 11 individual interviews with PCMs from two military treatment facilities in the U.S National Capital Region and 11 individual interviews with administrative sleep stakeholders (9 military and 2 civilian). Active duty service members, PCMs, and administrative stakeholders provided insight regarding expectations for sleep telehealth as well as suggestions to optimize the novel sleep telehealth platform. In terms of outcomes, ADSMs expected sleep telehealth to improve sleep and convenience. Primary care managers expected improved sleep and other comorbidities, enhanced operational readiness, and reduced mortalities among their patients. Administrators expected increased access to care, optimized utilization of health services, realized cost savings, reduced accidents and errors, and improved military performance. In terms of the platform, for ADSMs, desired characteristics included delivery of timely clinical reports, improved patient-provider communication, and enhanced continuity of care. For PCMs and administrators,an ideal sleep telehealth solution will improve the diagnosis and triage of sleep patients, save PCM time, be easy to use, and integrate with the electronic health record system. The proposed sleep telehealth platform appealed to nearly all participants as a significant force multiplier to enhance sleep disorder management in the military. Stakeholders offered valuable recommendations to optimize the platform to ensure its successful real-world implementation.


Innate immune induction and influenza protection elicited by a response-selective agonist of human C5a.
The anaphylatoxin C5a is an especially potent mediator of both local and systemic inflammation. However, C5a also plays an essential role in mucosal host defense against bacterial, viral, and fungal infection. We have developed a response-selective agonist of human C5a, termed EP67, which retains the immunoenhancing activity of C5a at the expense of its inflammatory, anaphylagenic properties. EP67 insufflation results in the rapid induction of pulmonary cytokines and chemokines. This is followed by an influx of innate immune effector cells, including neutrophils, NK cells, and dendritic cells. EP67 exhibits both prophylactic and therapeutic protection when tested in a murine model of influenza A infection. Mice treated with EP67 within a twenty-four hour window of non-lethal infection were significantly protected from influenza-induced weight loss. Furthermore, EP67 delivered twenty-four hours after lethal infection completely blocked influenza-induced mortality (0% vs. 100% survival). Since protection based on innate immune induction is not restricted to any specific pathogen, EP67 may well prove equally efficacious against a wide variety of possible viral, bacterial, and fungal pathogens. Such a strategy could be used to stop the worldwide spread of emergent respiratory diseases, including but not limited to novel strains of influenza.


Development of hydrocephalus in mice expressing the G(i)-coupled GPCR Ro1 RASSL receptor in astrocytes.
We developed a transgenic mouse line that expresses the G(i)-coupled RASSL (receptor activated solely by synthetic ligand) Ro1 in astrocytes to study astrocyte-neuronal communication. Surprisingly, we found that all transgenics expressing Ro1 developed hydrocephalus. We analyzed these mice in an effort to develop a new model of hydrocephalus that will further our understanding of the pathophysiology of the disease. Expression of Ro1 was restricted to astrocytes by crossing the transgenic hGFAP-tTA (tet transactivator behind the human glial fibrillary acidic protein promoter) mouse line with the transgenic tetO-Ro1/tetO-LacZ mouse line. This cross produced double-transgenic mice that expressed Ro1 in astrocytes. All double transgenics developed hydrocephalus by postnatal day 15, whereas single-transgenic littermate controls appeared normal. Hydrocephalic Ro1 mice displayed enlarged ventricles, partial denudation of the ependymal cell layer, altered subcommissural organ morphology, and obliteration of the cerebral aqueduct. Severely hydrocephalic mice also had increased levels of phospho-Erk and GFAP expression. Administration of doxycycline to breeding pairs suppressed Ro1 expression and the onset of hydrocephalus in double-transgenic offspring. Ro1 animals maintained on dox did not develop hydrocephalus; however, if taken off doxycycline at weaning, double-transgenic mice developed enlarged ventricles within 7 weeks, indicating that Ro1 expression also induces hydrocephalus in adults. This study discovered a new model of hydrocephalus in which the rate of pathogenesis can be controlled enabling the study of the pathogenesis of both juvenile and adult onset hydrocephalus.


The role of brain-derived neurotrophic factor (BDNF) in the development of neurogenic detrusor overactivity (NDO).
Neurogenic detrusor overactivity (NDO) is a well known consequence of spinal cord injury (SCI), recognizable after spinal shock, during which the bladder is areflexic. NDO emergence and maintenance depend on profound plastic changes of the spinal neuronal pathways regulating bladder function. It is well known that neurotrophins (NTs) are major regulators of such changes. NGF is the best-studied NT in the bladder and its role in NDO has already been established. Another very abundant neurotrophin is BDNF. Despite being shown that, acting at the spinal cord level, BDNF is a key mediator of bladder dysfunction and pain during cystitis, it is presently unclear if it is also important for NDO. This study aimed to clarify this issue. Results obtained pinpoint BDNF as an important regulator of NDO appearance and maintenance. Spinal BDNF expression increased in a time-dependent manner together with NDO emergence. In chronic SCI rats, BDNF sequestration improved bladder function, indicating that, at later stages, BDNF contributes NDO maintenance. During spinal shock, BDNF sequestration resulted in early development of bladder hyperactivity, accompanied by increased axonal growth of calcitonin gene-related peptide-labeled fibers in the dorsal horn. Chronic BDNF administration inhibited the emergence of NDO, together with reduction of axonal growth, suggesting that BDNF may have a crucial role in bladder function after SCI via inhibition of neuronal sprouting. These findings highlight the role of BDNF in NDO and may provide a significant contribution to create more efficient therapies to manage SCI patients.


Phytoplankton community structure changes during autumn and spring in response to environmental variables in Methana, Saronikos Gulf, Greece.
Phytoplankton community was investigated during two contrasting periods using offshore plankton samples in the volcanic area of Methana peninsula (Saronikos Gulf): the first at early autumn (warm period, September 2016) and the second one at early spring (cold period, March 2017). In order to investigate the phytoplankton community structure in the complex geo-biochemical conditions of the area, samples were collected from stations near the CO2 hydrothermal vents, at the hydrothermal sulfur and radioactive springs and at a fishery nearby Methana town. Three major phytoplankton groups, Bacillariophyceae, Dinophyceae, and Prymnesiophyceae, were studied, using inverted microscopy. In early autumn, Dinophyceae were dominant in the majority of the stations with cell concentrations of Prorocentrum spp. up to ~ 35.5 × 103 cells l-1. In early spring, the dominant class was Bacillariophyceae with dominant genus Nitzschia/Pseudo-nitzschia presenting cell concentrations up to ~ 33.9 × 103 cells l-1. Furthermore, Prymnesiophyceae appeared in both spring and autumn samples with small fluctuations. Total phytoplankton cell concentrations followed a seasonal trend, presenting slightly lower values in the hydrothermal-effected area in comparison with the broader Saronikos Gulf, confirming the prevalence of oligotrophic conditions. Seasonal variation was very strong, revealing an association with water temperature and nutrient content. Those environmental variables proved to have a strong effect that was reflected in the phytoplankton community structure.


Abnormal His-Purkinje system conduction leading to complete atrioventricular block in patients with hypertrophic cardiomyopathy: a report of 3 cases.
This case report describes three hypertrophic cardiomyopathy patients with abnormal His-Purkinje conduction and complete atrioventricular block with attacks of syncope and cardiopulmonary arrest. Although arrhythmias are common in hypertrophic cardiomyopathy, complete atrioventricular block is very rare. Prolonged QRS duration and abnormal His-Purkinje system conduction may result in complete atrioventricular block.


A forensic-psychiatric study of sexual offenders in Rio de Janeiro, Brazil.
Sexual violence is defined as any sexual act forced upon a person who did not give his or her consent. Our objective is to investigate the socio-demographic features, clinical correlates, criminal behaviour characteristics, and the level of penal responsibility of sexual offenders who were referred to forensic psychiatric assessment in the city of Rio de Janeiro, Brazil. This is a cross-sectional descriptive study. All written reports made in the year of 2008 by court-appointed psychiatric experts on individuals charged with having committed sexual crimes and referred to the main forensic hospital in the State of Rio de Janeiro, Brazil, for assessment were reviewed. Forty-four expert reports were identified. All alleged offenders were male. Nineteen (43.2%) offenders did not receive any psychiatric diagnostic. Nine offenders (20.4%) were diagnosed with mental retardation. In 16 cases (36.4%), some form of mental or neurological disorder was diagnosed. Thirty-one (70.4%) offenders were considered fully responsible, eight (18.2%) partially responsible, and five (11.4%) not responsible by reason of insanity. The sexual crimes allegedly perpetrated by the offenders were rape (n=14, 32%), attempted rape (n=4, 9%), indecent assault (n=26, 59%), and indecent exposure (n=5, 11.4%). In 10 cases (22.7%), the offender was under alcohol influence at the moment of the crime. The profile of Brazilian sex offenders subject to forensic psychiatric assessment were male, caucasian, single, working part time, with no mental disorder, who perpetrated indecent assault.


Identifying targets of selection in mosaic genomes with machine learning: applications in Anopheles gambiae for detecting sites within locally adapted chromosomal inversions.
Chromosomal inversions are important structural changes that may facilitate divergent selection when they capture co-adaptive loci in the face of gene flow. However, identifying selection targets within inversions can be challenging. The high degrees of differentiation between heterokaryotypes, as well as the differences in demographic histories of collinear regions compared with inverted ones, reduce the power of traditional outlier analyses for detecting selected loci. Here, we develop a new approach that uses discriminant functions informed from inversion-specific expectations to classify loci that are under selection (or drift). Analysis of RAD sequencing data we collected in a classic dipteran species with polymorphic inversion clines-Anopheles gambiae, a malaria vector species from sub-Saharan Africa-demonstrates the benefits of the approach compared with traditional outlier analyses. We focus specifically on two polymorphic inversions, the 2La and 2Rb arrangements that predominate in dry habitats and the 2L+(a) and 2R+(b) arrangements in wet habitats, which contrast with the minimal geographic structure of SNPs from collinear regions. With our approach, we identify two strongly selected regions within 2La associated with dry habitat. Moreover, we also show that the prevalence of selection is greater in the arrangement 2L+(a) that is associated with wet habitat (unlike presumed importance of selective divergence associated with the shift of the mosquitoes into dry habitats). We discuss the implications of these results with respect to studies of rapid adaptation in these malaria vectors, and in particular, the insights our newly developed approach offers for identifying not only potential targets of selection, but also the population that has undergone adaptive change.


Latest Advances in the Treatment of Bicuspid Aortic Valve.
Bicuspid aortic valve (BAV) is the most frequent congenital cardiac defect, and affects 0.5-2% of live births. Almost half of BAV subjects develop different degrees of valvular dysfunction during their lifetime. In both echocardiographic cohorts and surgical series, pure aortic regurgitation is significantly less common than stenosis. BAV also carries a higher risk of aortic aneurysm, aortic dissection or aortic valve endocarditis compared to the general population. Once aortic insufficiency reaches threshold criteria for surgical treatment, the valve has to be replaced (conventional aortic valve replacement, the outcomes of which are well established) or repaired. Repair techniques for regurgitant BAVs and valve-sparing surgery for BAV-related aneurysms have evolved remarkably over the past several decades. Improvements in our understanding of the mechanisms of normal and pathological BAV function and the development of criteria and techniques to address all the pathologic components of valve and root have supported better repair results. The more frequent stenotic BAV is treated by prosthetic valve replacement or, in recent years, by trans-catheter prosthetic replacement (TAVR), the application of which in the BAV setting is increasing, as with tricuspid aortic valve (TAV) stenosis, especially since indications are extended to medium-risk patients. It has been reported that the risk of paravalvular leak and/or prosthesis malposition is higher in BAV than in TAV stenosis, due to the more elliptical annulus and the calcified raphe of the bicuspid valve. New-generation balloon-expandable devices seem to be capable of lowering the rates of these complications. As research in this field keeps filling in the gaps in current knowledge about bicuspid malformation and its common complications, further advancements in their treatment are awaited.


[Obesity-related glomerulopathy: Mechanisms of development, clinical course].
Obesity and overweight are recognized as epidemics of non-communicable diseases in the 21st century. The kidneys are a target organ for obesity, damage to which is considered to be an independent risk factor for the development of renal failure. Obesity-related glomerulopathy (OGP) is one of the types of renal injury in obesity, which is characterized by the development of proteinuria in patients with a body mass index (BMI) of >30 kg/m2 in the absence of other causes of kidney damage. The pathogenesis of OGP is multifactorial. It is associated with intrarenal hemodynamic disorders - the development of renal hyperfiltration, the damaging action of adipose tissue hormones (hyperleptinemia, activation of the renin-angiotensin-aldosterone system, decreased production of adiponectin); with ectopic lipid accumulation in the kidney. The morphological pattern of OGP is characterized by a low glomerular density (oligonephronia) that leads to glomerular and tubular hypertrophy; by the development of perihilar focal segmental glomerulosclerosis (FSGS), obvious podocyte damages, and the development of a fatty kidney. The clinical picture of OGP is characterized by the slow and gradual development of albuminuria, not exceeding Stage A3 (300-1999 mg/day). Approximately one-third of patients develop partial nephrotic syndrome with massive proteinuria, but without edema and hypoproteinemia. Complete nephrotic syndrome is observed in not more than 6% of patients with OGP. In the course of the disease, 50% of patients develop hypertension and more than 80% do dyslipidemia. Stages IV-V chronic kidney disease may develop 20-30 years after the disease occurs.


Genomic localization of the human gene encoding Dr1, a negative modulator of transcription of class II and class III genes.
Dr1 is a nuclear protein of 19 kDa that exists in the nucleoplasm as a homotetramer. By binding to TBP (the DNA-binding subunit of TFIID, and also a subunit of SL1 and TFIIIB), the protein blocks class II and class III preinitiation complex assembly, thus repressing the activity of the corresponding promoters. Since transcription of class I genes is unaffected by Dr1. it has been proposed that the protein may coordinate the expression of class I, class II and class III genes. By somatic cell genetics and fluorescence in situ hybridization, we have localized the gene (DR1), present in the genome of higher eukaryotes as a single copy, to human chromosome region 1p21-->p13. The nucleotide sequence conservation of the coding segment of the gene, as determined by Noah's ark blot analysis, and its ubiquitous transcription suggest that Dr1 has an important biological role, which could be related to the negative control of cell proliferation.


Pre-participation gynecological evaluation of female athletes: a new proposal.
To propose the inclusion of a gynecological investigation during the evaluation of athletes before competitions, using a specific instrument called the Pre-participation Gynecological Examination (PPGE). The study assessed 148 athletes, mean age of 15.4±2.0 years, who engaged in eight different sports modalities, and who responded to a questionnaire named Pre-Participation Gynecological Examination (PPGE), to the International Consultation on Incontinence Questionnaire - Short Form (for urinary loss), and to the Eating Attitudes Test (for eating disorders). Fifty percent of the participants reported irregular menstrual intervals, 23.0% did not know about sexually transmitted diseases, and 72.4% denied having, at least, an annual gynecological appointment. The study identified 18.2% who had urinary loss, and 15% presented with an increased risk of eating disorders. Moreover, 89.9% were not familiar with the occurrence of urinary incontinence in athletes and did not know that they were susceptible to the female athlete triad. A total of 87.1% of them stated that would not mention these issues to their coaches even if this would improve their health or performance. The Pre-Participation Gynecological Examination can be considered an easy-to-apply instrument that allowed the diagnosis of alterations often underestimated by the athletes themselves. After its application, the alterations were identified, and determined the athletes' referral to appropriate evaluation and treatment.


Acute Demyelinating Polyneuropathy as Presentation of Hereditary Neuropathy With Liability to Pressure Palsies in a Patient Who Exercised Regularly in the Army.
Acute generalized neuropathy as the presenting manifestation of hereditary neuropathy with liability to pressure palsies (HNPP) is rare. We report a 19-year-old Army recruit who exercised regularly for 9 months and presented with 2 weeks of numbness, tingling, and weakness in both upper and lower extremities, starting 2 weeks after influenza vaccination and 1 day after vigorous exercise. Based on acute onset, clinical examination and electrophysiological findings, Guillain-Barre syndrome was diagnosed, and intravenous immunoglobulin was administered with minimal improvement. The presence of high foot arches and scapular winging raised suspicion of HNPP, confirmed by genetic testing. The role of the influenza vaccine in the development of symptoms is discussed. This case highlights the fact that HNPP can present as an acute generalized neuropathy even in people who train regularly. Careful history, physical examination, and evidence of entrapment neuropathies in nerve conduction study can aid in the diagnosis.


Month of birth and height of Spanish middle-aged men.
We examined whether body height differs in Spain, a country having a high number of hours of sunlight, between middle-aged males and females born during the months with the longest and those born in the months with the shortest periods of daylight hours. We used data from a cross-sectional survey that documented standardized measurements of height and other variables for a 2021-person random multi-stage sample representative of the Spanish population aged 35-64 years. The relationship between height and month of birth was analysed by multiple linear regression, adjusting for age, occupation and type of residence. Male adults born in summer proved to be 1.7 cm taller than their counterparts born in winter (95% confidence interval 0.2-3.3 cm, p = 0.03). This relationship was most marked for those whose occupation was non-manual (2.1 cm, p = 0.04 vs 1.4cm, p = 0.2 in manual occupations). No significant (p = 0.8) or relevant (0.16 cm) summer- and winter-related differences in height were found in women. These results are compatible with the hypothesis that adult male height could be partially influenced by physical environmental factors such as the action of sunlight during the early stages of life.


Dopamine transporter polymorphism modulates oculomotor function and DAT1 mRNA expression in schizophrenia.
Smooth pursuit eye movement (SPEM) deficit is an established schizophrenia endophenotype with a similar neurocognitive construct to working memory. Frontal eye field (FEF) neurons controlling SPEM maintain firing when visual sensory information is removed, and their firing rates directly correlate with SPEM velocity. We previously demonstrated a paradoxical association between a functional polymorphism of dopamine signaling (COMT gene) and SPEM. Recent evidence implicates the dopamine transporter gene (DAT1) in modulating cortical dopamine and associated neurocognitive functions. We hypothesized that DAT1 10/10 genotype, which reduces dopamine transporter expression and increases extracellular dopamine, would affect SPEM. We examined the effects of DAT1 genotype on: Clinical diagnosis in the study sample (n = 418; 190 with schizophrenia), SPEM measures in a subgroup with completed oculomotor measures (n = 200; 87 schizophrenia), and DAT1 gene expression in FEF tissue obtained from postmortem brain samples (n = 32; 16 schizophrenia). DAT1 genotype was not associated with schizophrenia. DAT1 10/10 genotype was associated with better SPEM in healthy controls, intermediate SPEM in unaffected first-degree relatives of schizophrenia subjects, and worse SPEM in schizophrenia subjects. In the gene expression study, DAT1 10/10 genotype was associated with significantly reduced DAT1 mRNA transcript in FEF tissue from healthy control donors (P < 0.05), but higher expression in schizophrenia donors. Findings suggest regulatory effects of another gene(s) or etiological factor in schizophrenia, which modulate DAT1 gene function.


Lipopolysaccharide-induced liver injury in rats treated with the CYP2E1 inducer pyrazole.
Elevated LPS and elevated cytochrome P-450 2E1 (CYP2E1) in liver are two major independent risk factors in alcoholic liver disease. We investigated possible synergistic effects of the two risk factors in causing oxidative stress and liver injury. Sprague-Dawley rats were injected intraperitoneally with pyrazole (inducer of CYP2E1) for 2 days, and then LPS was injected via tail vein. Other rats were treated with pyrazole alone or LPS alone or saline. Eight hours later, blood was collected and livers were excised. Pathological evaluation showed severe inflammatory responses and necroses only in liver sections from rats in the pyrazole plus LPS group; blood transaminase levels were significantly elevated only in the combination group. Activities of caspase-3 and -9 and positive terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining were highest in the LPS alone and the LPS plus pyrazole group, with no significant difference between the two groups. Lipid peroxidation and protein carbonyls in liver homogenate as well as in situ superoxide production were maximally elevated in the LPS plus pyrazole group. Levels of nitrite plus nitrate and inducible nitric oxide (NO) synthase (iNOS) content were comparably elevated in LPS alone and the LPS plus pyrazole group; however, 3-nitrotyrosine adducts were elevated in the combined group but not the LPS group. It is likely that LPS induction of iNOS, which produces NO, coupled to pyrazole induction of CYP2E1 which produces superoxide, sets up conditions for maximal peroxynitrite formation and production of 3-nitrotyrosine adducts. CYP2E1 activity and content were elevated in the pyrazole and the LPS plus pyrazole groups. Immunohistochemical staining indicated that distribution of CYP2E1 was in agreement with that of necrosis and production of superoxide. These results show that pyrazole treatment enhanced LPS-induced necrosis, not apoptosis. The enhanced liver necrosis appears to involve an increase in oxidative and nitrosative stress generated by the combination of LPS plus elevated CYP2E1 levels.


Endoscopic management of nonampullary duodenal polyps.
Duodenal polyps are a rare finding in patients presenting for gastroscopy, being found in 0.3-4.6% of cases. The majority of patients are asymptomatic. The most common lesions necessitating removal are duodenal adenomas which should be differentiated from other mucosal lesions such as ectopic gastric mucosa, and submucosal lesions such as carcinoids and gastrointestinal stromal tumours (GISTs). Adenomas can occur sporadically or as part of a polyposis syndrome. Both groups carry malignant potential but this is higher in patients with a polyposis syndrome. The majority of sporadic duodenal adenomas are flat or sessile and occur in the second part of the duodenum. Historically duodenal adenomas have been managed by radical surgery, which carried significant mortality and morbidity, or more conservative local surgical excision which resulted in high local recurrence rates. There is growing evidence for the use of endoscopic mucosal resection (EMR) techniques for treatment of sporadic nonampullary duodenal adenomas, with good outcomes and low complication rates. Endoscopic submucosal dissection (ESD) carries greater risk of complications and should be reserved for experts in this technique. Patients with sporadic duodenal adenomas carry an increased risk of colonic neoplasia and should be offered colonoscopy. The impact of endoscopic resection on the course of polyposis syndromes such as familial adenomatous polyposis (FAP) needs further study.


Raman spectroscopic evidence of tissue restructuring in heat-induced tissue fusion.
Heat-induced tissue fusion via radio-frequency (RF) energy has gained wide acceptance clinically and here we present the first optical-Raman-spectroscopy study on tissue fusion samples in vitro. This study provides direct insights into tissue constituent and structural changes on the molecular level, exposing spectroscopic evidence for the loss of distinct collagen fibre rich tissue layers as well as the denaturing and restructuring of collagen crosslinks post RF fusion. These findings open the door for more advanced optical feedback-control methods and characterization during heat-induced tissue fusion, which will lead to new clinical applications of this promising technology.


Effects of furrow irrigation on the growth, production, and water use efficiency of direct sowing rice.
Rice farming is the major crop production in Asia and is predicted to increase significantly in the near future in order to meet the demands for the increasing human population. Traditional irrigation methods used in rice farming often result in great water loss. New water-saving methods are urgently needed to reduce water consumption. Three field and pot experiments were conducted to evaluate the furrow irrigation (FI) system to improve water use efficiency (WUE) and production of direct sowing rice in southern China. Compared to the conventional irrigation (CI) system (continuous flooding irrigation), for every square hectometer of rice field, the FI system reduced water use by 3130 m3, or 48.1%, and increased grain production by 13.9% for an early cultivar. For a late cultivar, the FI system reduced water use by 2655 m3, or 40.6%, and an increase of grain production by 12.1%. The improved WUE in the FI system is attributed to (1) a significant reduction of irrigation rate, seepage, evaporation, and evapotranspiration; (2) a significant reduction in the reduced materials, such as ferrous ion (Fe2+), and therefore an increase in the vitality of the root system, evident by the increases in the number of white roots by 32.62%, and decreases in the number of black roots by 20.04% and yellow roots by 12.58%; the use of the FI system may also reduce humidity of the rice field and enhance gas transport in the soil and light penetration, which led to reduced rice diseases and increased leaf vitality; and (3) increases in tiller and effective spikes by 11.53% and the weight per thousand grains by 1.0 g. These findings suggest that the shallow FI system is a promising means for rice farming in areas with increasing water shortages.


What Does Venous Thromboembolism Mean in the National Surgical Quality Improvement Program?
Venous thromboembolism (VTE) affects an estimated 350,000 to 600,000 individuals and causes approximately 100,000 deaths annually in the United States. Postoperative VTE is a core measure reported by The American College of Surgeons' National Surgical Quality Improvement Program (NSQIP). The objective of this research was to assess the validity of VTE events reported by NSQIP. This is a retrospective analysis using NSQIP data from January 2006 through December 2018 and the electronic health record system data from five adult hospitals in the Johns Hopkins Health System. We included patients aged 18 years and older with a VTE event identified in our NSQIP data set. The main outcome measure was the proportion of valid VTE events, defined as concordant between the NSQIP data set and medical chart review for clinical documentation. Of 474 patients identified in our NSQIP database with a VTE, 26 (5.5%) did not meet the strict NSQIP definition of VTE. Nine had a preoperative history of DVT and no new postoperative event, seven had a negative workup for VTE, six had a peripheral arterial thrombus, two did not receive or refused therapy, one had an aortic thrombus, and one had a venous thrombosis in a surgical flap. We identified a considerable number of surgical patients misclassified as having a VTE in NSQIP, when did not truly. This highlights the need to improve definition specificity and standardize processes involved in data extraction, validation, and reporting to provide unbiased data for use in quality improvement.


[Splenosis and pelvic pain. A report of a case and literature review].
Initially described by Buchbinder and Lipkoff in 1929, esplenosis is the transplant of the splenic heterotopy weave in the abdominal cavity. It is observed after the splenic traumatic rupture and appendectomy. It occurs also during the embryonic development. The most frequent places where it takes place are: the intrathoraxic cavity, intraperitoneal, retroperitoneo, and brain. Although the presence of this ectopic splenic weave is symptomatic, this pathology can be evident by pain in the pelvis or it can be confused with other pathologies such as hemangiomas of intestine, and endometriosis including metastasis carcinoma. It is impossible to predict which patients will develop the splenosis after the splenic trauma. The time of rupture or damage of the splectonomy and the amount of blood in the peritoneal cavity are not related with the number of implants. The symptoms are the clue. When the splenosis is diagnosed incidentally in a symptomatic patient, the complete surgery removal is not indicated. However this surgery is recommended when the abdominal pain or the diagnosis is uncertain. In this paper a case with a secondary pelvic pain, probably due to a tubaric abortion, agreeing with secondary splenosis and a traumatic splenic rupture, is reported.


Narrowband and tunable anomalous transmission filters for spectral monitoring in the extreme ultraviolet wavelength region.
We present the first experimental demonstration of a novel type of narrowband and wavelength-tunable multilayer transmission filter for the extreme ultraviolet (EUV) region. The operating principle of the filter is based on spatially overlapping the nodes of a standing wave field with the absorbing layers within the multilayer structure. For a wavelength with a matching node pattern, this increases the transmission as compared to neighboring wavelengths where anti-nodes overlap with the absorbing layers. Using Ni/Si multilayers where Ni provides strong absorption, we demonstrate the proper working of such anomalous transmission filter. The demonstration is carried out at the example of 13.5 nm wavelength and at normal incidence, providing a 0.27 nm-wide transmission peak. We also demonstrate wavelength tunability by operating the same Ni/Si filter at different wavelengths by varying the angle of incidence. As the multilayer filter is directly deposited on the active area of an EUV-sensitive photodiode, this provides an extremely compact device for easy spectral monitoring in the EUV. The transmission spectrum of the filter is modeled and found to be in good agreement with the experimental data. The agreement proves that such filters and compact monitoring devices can be straightforwardly designed and fabricated, as desired, also for other EUV wavelengths, bandwidths and angles of incidence, thereby showing a high potential for applications.


Mortality after hospitalization for heart failure in blacks compared to whites.
Heart failure (HF) disproportionately affects black compared to white Americans, and overall mortality from HF is greater among blacks. Paradoxically, mortality rates after a hospitalization for HF are lower in black than in white patients. These racial differences might reflect hospital, physician, and patient factors and could have implications for comparative hospital profiles. We identified published studies reporting the posthospitalization mortality for black and white patients with a discharge diagnosis of HF and conducted random-effects meta-analyses with the outcome of all-cause mortality. We included 29 cohorts of hospitalized black and white patients with HF. The unadjusted mean mortality rate after HF hospitalization for black and white patients, respectively, was 6% and 9% for in-hospital, 6% and 10% for 30-day, 10% and 15% for 60- to 180-day, 28% and 34% for 1-year, and 41% and 47% for >1-year follow-up, respectively. The unadjusted combined odds ratios for mortality in black versus white patients ranged from 0.48 for in-hospital (95% confidence interval [CI] 0.45 to 0.51) to 0.77 after >1 year follow-up (95% CI 0.75 to 0.79). In meta-analyses using adjusted data, the combined odds ratio was 0.68 for short-term mortality (95% CI 0.63 to 0.74), and the combined hazard ratio was 0.84 for long-term mortality (95% CI 0.77 to 0.91). In conclusion, mortality after hospitalization for HF was 32% lower during short-term follow-up and 16% lower during long-term follow-up for black than for white patients. The mortality differences imply unmeasured differences by race in clinical severity of illness at hospital admission and might lead to biased hospital mortality profiles.


Presence of Five Chemotherapeutic Drugs in Breast Milk as a Guide for the Safe Use of Chemotherapy During Breastfeeding: Results From a Case Series.
Little is known about infant's safety of chemotherapy during breastfeeding where evidence is limited to a few case reports. This lack of knowledge has led to a general tendency to advise against breastfeeding during cytotoxic therapy despite the overwhelming benefits that breastfeeding offers to both the mothers and their children. In this case series, the presence of five chemotherapies in breast milk was determined. The aim was to obtain insight into the presence of these drugs in breast milk to inform and help clinicians in making informed decisions for women who want to breastfeed. Three patients collected 24-hour samples of breast milk every day for 1, 2, or 3 weeks after chemotherapy, 210 in total. After determination of drug concentrations, the infant daily dose, relative daily infant dose (RID%) and cumulative RID were calculated. Cumulative RIDs in patients varied from 10% to values lower than 1%. Rich data allowed us to design a table which gives predictions on the amount of days that breast milk has to be discarded to reach cumulative RIDs below 5, 1, and 0.1% for each compound. For cyclophosphamide, paclitaxel, and carboplatin, cumulative RIDs below 1 or 0.1% are reached if breast milk is discarded for 1-3 days after administration. This might suggest that breastfeeding in between cycles is an option. However, other pharmacological parameters should also be taken into consideration. For doxorubicin, also the levels of the active metabolite doxorubicinol need quantification. Similarly, breastfeeding during treatment with cisplatin might give substantial exposure and we advise caution.


A β-glucuronidase (GUS) based cell death assay.
We have developed a novel transient plant expression system that simultaneously expresses the reporter gene, β-glucuronidase (GUS), with putative positive or negative regulators of cell death. In this system, N. benthamiana leaves are co-infiltrated with a 35S driven expression cassette containing the gene to be analyzed, and the GUS vector pCAMBIA 2301 using Agrobacterium strain LBA4404 as a vehicle. Because live cells are required for GUS expression to occur, loss of GUS activity is expected when this marker gene is co-expressed with positive regulators of cell death. Equally, increased GUS activity is observed when anti-apoptotic genes are used compared to the vector control. As shown below, we have successfully used this system in our lab to analyze both pro- and anti-death players. These include the plant anti-apoptotic Bcl-2 Associated athanoGene (BAG) family, as well as, known mammalian inducers of cell death, such as BAX. Additionally, we have used this system to analyze the death function of specific truncations within proteins, which could provide clues on the possible post-translational modification/activation of these proteins. Here, we present a rapid and sensitive plant based method, as an initial step in investigating the death function of specific genes.


The use of breast milk iodine concentration in the first week of lactation as a biomarker of iodine status in breast-feeding women.
Breast milk iodine concentration (BMIC) is a promising indicator of iodine status in lactating women. However, there are limited data on its usefulness to reflect maternal iodine deficiency. Therefore, the aim of our study was to assess iodine concentration in breast milk and urine samples in exclusively breast-feeding women. Eligible pregnant women undergoing routine antenatal care in a large hospital in Shaanxi Province, China, were followed up from the third trimester of pregnancy until the first week of lactation. Urine samples (20 ml) were collected during pregnancy and lactation. Iodine concentration in samples was measured based on Sandell-Kolthoff reaction. Breast milk samples (5 ml) were provided during lactation. A receiver operating curve (ROC) was constructed to determine the diagnostic performance of BMIC. An iodine-specific FFQ was completed twice during pregnancy and lactation. A total of 200 women completed the study. The overall median BMIC was 89 μg/l, indicating iodine sufficiency (i.e. BMIC reference range between 60 and 465 μg/l). Women reported similar median urinary iodine concentration (UIC) during pregnancy and lactation (112 and 113 μg/l, respectively), but their iodine status differed - mild-to-moderate iodine deficiency during pregnancy and iodine sufficiency during lactation. The ROC for BMIC using UIC as a reference standard was 0·755 (95 % CI: 0·644, 0·866). In conclusion, this study demonstrated that women were iodine sufficient in the first week of lactation as assessed by UIC, which was consistent with BMIC. These findings suggested that BMIC is a useful biomarker to assess iodine status in lactating women.


Myelin-associated glycoprotein inhibits neurite/axon growth and causes growth cone collapse.
We have previously shown that myelin-associated glycoprotein (MAG) inhibits neurite growth from a neuronal cell line. In this study we show that 60% of axonal growth cones of postnatal day 1 hippocampal neurons collapsed when they encountered polystyrene beads coated with recombinant MAG (rMAG). Such collapse was not observed with denatured rMAG. Neurite growth from rat embryonic hippocampal and neonatal cerebellar neurons was also inhibited about 80% on tissue culture substrates coated with rMAG. To investigate further the inhibitory activity of MAG in myelin, we purified myelin from MAG-deficient mice and separated octylglucoside extracts of myelin by diethylaminoethyl (DEAE) ion-exchange chromatography. Although there was no significant difference in neurite growth on myelin purified from MAG-/- and MAG+/+ mice, differences were observed in the fractionated material. The major inhibitory peak that is associated with MAG in normal mice was significantly reduced in MAG-deficient mice. These results suggest that although MAG contributes significantly to axon growth inhibition associated with myelin, its lack in MAG-deficient mice is masked by other non-MAG inhibitors. Axon regeneration in these mice was also examined after thoracic lesions of the corticospinal tracts. A very small number of anterogradely labeled axons extended up to 13.2 mm past the lesion in MAG-/- mice. Although there is some enhancement of axon generation, the poor growth after spinal cord injury in MAG-/- mice may be due to the presence of other non-MAG inhibitors. The in vitro studies, however, provide the first evidence that MAG modulates growth cone behavior and inhibits neurite growth by causing growth cone collapse.


ISI values and interhemispheric differences in patients with ischemic cerebrovascular disease; correlations with clinical and angiographic findings.
Xenon 133 inhalation CBF studies of one hundred patients with ischemic cerebrovascular disease in the territory of the carotid artery were compared in an attempt to gain more insight into the collateral capacity, especially in those with a stenosis or occlusion of one of the major arteries. Asymmetry of the ISI values for the two hemispheres was expressed as a ratio. High ratios (greater ISI asymmetries) were found for patients with an occlusion of the internal carotid or middle cerebral artery, especially--but not exclusively--those with the more severe clinical symptoms. It also appeared that even when the patient is in a good clinical condition, an elevated ratio reflects insufficiency of the collateral supply to the affected side. The ISI values for individual patients seem to be less useful, partly due to the variable age dependency of this flow parameter.


Serum Albumin as a Biomarker of Pulmonary Sarcoidosis Chronicity.
The duration of sarcoidosis is associated with a higher risk of irreversible pulmonary fibrosis. Sarcoidosis shows diverse clinical presentations, which may lead to a delayed diagnosis due to lack of a specific diagnostic test. Biomarkers of sarcoidosis duration have not been previously explored. A retrospective study was conducted to investigate independent biomarkers of pulmonary sarcoidosis duration. A total of 108 cases with pulmonary sarcoidosis (mean age 53.4 years; 76.9% females; average duration of sarcoidosis 12 years) were included in the study. We found significant correlation between the duration of sarcoidosis and serum albumin levels (r=-0.414, p=0.0001), sedimentation rate (r=0.375, p=0.001), pulmonary artery systolic pressure (r= 0.468, p=0.003), diffusion capacity (r=-0.334, p=0.002), and age (r=0.492, p=0.0001). A multivariate linear regression analysis revealed that serum albumin levels (β=-5.242, 95% confidence interval [CI] -8.372 to -2.112, p=0.001) and age (β=0.367, 95% CI 0.164 to 0.570, p=0.001) were independent correlates of sarcoidosis duration. A receiver operating characteristics curve analysis for prediction of sarcoidosis of a >10 years duration gave an area under curve (AUC) of 0.722 (95% CI 0.620-0.824, p<0.0001) for serum albumin and an AUC of 0.665 (95% CI 0.561-0.768, p<0.004) for age. An albumin level <2.4 gm/dL yielded a 90.5% sensitivity and 98.2% specificity for predicting sarcoidosis of >10 years duration. In comparison, the patient age of 51.5 years yielded a 70.2% sensitivity and 50% specificity for predicting patients with sarcoidosis for >10 years. The serum albumin level may be a biomarker of pulmonary sarcoidosis duration and chronicity of disease. Further investigations are required to confirm its predictive ability.


Musical hallucinations in patients with Lyme disease.
Musical hallucinations are poorly understood auditory hallucinations that occur in patients with otologic or neurologic diseases. We report the first cases of musical hallucinations in two patients with neurologic Lyme disease. Both subjects were women with clinical and laboratory evidence of chronic Lyme disease, progressive neurologic dysfunction, and abnormal magnetic resonance imaging of the brain. There was no evidence of hearing loss in either case. Musical hallucinations had a sudden onset and took the form of patriotic or operatic music. The auditory hallucinations disappeared with intravenous (i.v.) antibiotic therapy in both patients, but the hallucinations recurred when i.v. antibiotic therapy was discontinued in one case. Response to therapy was accompanied by an increase in the CD57 lymphocyte subset in one patient, whereas recurrent hallucinations were associated with persistently low CD57 levels in the other case. We conclude that musical hallucinations may be associated with neurologic Lyme disease. These auditory hallucinations appear to respond to i.v. antibiotic therapy. Patients with musical hallucinations of unknown cause should be tested for infection with the Lyme disease spirochete.


Influence of indoor climate on the sick building syndrome in an office environment. The Danish Indoor Climate Study Group.
The influence of indoor climate factors on symptoms of the sick building syndrome was investigated in Greater Copenhagen, Denmark. Altogether, 2369 office workers in 14 buildings, where indoor climate measurements were made, filled out a questionnaire. Multivariate logistic regression analyses of the multifactorial effects on the prevalence of work-related mucosal irritation and work-related general symptoms among the office workers showed that the concentration of macromolecular organic floor dust, the floor covering, the number of workplaces in the office, the age of the building, the type of ventilation, and two easily recognizable factors, the shelf factor and the fleece factor, were associated with the prevalence of symptoms.


Inhibition of transcription blocks cell cycle progression of NIH3T3 fibroblasts specifically in G1.
We have analysed the role of RNA polymerase II-dependent transcription in cell cycle progression. Time-lapse video recording and cytogenetic analysis were used to determine the sensitivity of NIH3T3 cells to the RNA polymerase II inhibitor alpha-amanitin at different stages of the cell cycle. Our results show that alpha-amanitin blocks cells specifically in G1, irrespective of the concentration within the range of 3 to 30 micrograms/ml. This indicates that transcription in G1 is required to overcome a restriction point located in this phase of the cell cycle. In agreement with this conclusion is the requirement for an uninhibited protein synthesis during G1 progression. In addition, the insensitivity of S-phase cells to RNA polymerase II inhibition suggests that the transcription of genes thought to be normally induced during S/G2 is not required for the completion of an ongoing cell cycle. S/G2 progression was however clearly dependent on protein synthesis. This suggests that cells exposed to alpha-amanitin are able to complete their cell cycle because sufficiently high levels of mRNA are present in S/G2 due to basal level transcription, or are left from preceding cell cycles. It is therefore unlikely that transcriptional regulation in S or G2 plays a crucial role in the control of cell cycle progression in NIH3T3 cells.


Facilitators, Barriers, and Outcomes of Self-Initiated HIV Testing: An Integrative Literature Review.
HIV testing is an essential tool for identifying people at risk for HIV infection and linking those who are infected to care. Despite the recommendation for routine HIV testing for people who are vulnerable to HIV infection, healthcare professionals experience difficulties initiating discussions related to sexual health and recommending HIV testing. Healthcare professionals not offering HIV testing is a frequently reported reason for delays in testing. Self-initiated HIV testing is understudied and vital to improving HIV testing rates, treatment, and the process of HIV prevention. The main aim of this integrative literature review is to identify facilitators, barriers, and outcomes of self-initiated HIV testing. A search of PubMed, CINAHL, PsycINFO, EBSCO host, and Google Scholar, revealed 31 studies that met the inclusion criteria. Self-initiated HIV testing is voluntarily requested and completed by individuals either using self-testing kits or in a setting that provides HIV testing. Perception of susceptibility to HIV infection, privacy, access to HIV testing sites or self-testing kits, and knowledge related to HIV infection and testing, were some of the salient facilitators and barriers to self-initiated HIV testing. Findings from our review indicate several benefits to self-initiated HIV testing, including early identification of acute HIV infection, increased likelihood for the uptake of HIV prevention interventions, and a reduction in sexual risk behaviors. Nursing initiatives geared toward promoting self-initiated HIV testing will lead to prompt diagnoses and linkages to treatment which will further improve nursing care and a variety of health outcomes.


A COVID-19 risk score combining chest CT radiomics and clinical characteristics to differentiate COVID-19 pneumonia from other viral pneumonias.
With the continued transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout the world, identification of highly suspected COVID-19 patients remains an urgent priority. In this study, we developed and validated COVID-19 risk scores to identify patients with COVID-19. In this study, for patient-wise analysis, three signatures, including the risk score using radiomic features only, the risk score using clinical factors only, and the risk score combining radiomic features and clinical variables, show an excellent performance in differentiating COVID-19 from other viral-induced pneumonias in the validation set. For lesion-wise analysis, the risk score using three radiomic features only also achieved an excellent AUC value. In contrast, the performance of 130 radiologists based on the chest CT images alone without the clinical characteristics included was moderate as compared to the risk scores developed. The risk scores depicting the correlation of CT radiomics and clinical factors with COVID-19 could be used to accurately identify patients with COVID-19, which would have clinically translatable diagnostic and therapeutic implications from a precision medicine perspective.


High serum erythropoietin level is associated with smaller infarct size in patients with acute myocardial infarction who undergo successful primary percutaneous coronary intervention.
We investigated whether a higher serum erythropoietin (EPO) level in patients with acute myocardial infarction (MI) subjected to successful primary percutaneous coronary intervention (PCI) can predict a smaller infarct size determined by creatine kinase (CK) release. Erythropoietin has been shown to protect cardiomyocytes from ischemia-reperfusion injury in rodents. We prospectively studied 101 patients with first MI who received successful primary PCI within 12 h from the onset of MI. Blood samples were collected to examine the serum EPO level after the primary PCI and within 24 h from the onset of MI. The peak CK level and cumulative CK release were significantly lower in the above-median EPO group than in the below-median EPO group. Thrombolysis In Myocardial Infarction (TIMI) grades and collateral grades before PCI, infarct-related coronary arteries, time to the successful reperfusion from the onset of MI, and serum creatinine levels were similar in the two EPO groups. A stepwise multiple regression analysis revealed that the absolute serum EPO level (mU/ml) as well as TIMI grades after PCI and preinfarction angina was an independent predictor for the cumulative CK release. These data suggest that a high endogenous EPO level can predict a smaller infarct size in patients with acute MI subjected to successful primary PCI. This might be attributed to the potentially protective effect of endogenous EPO against ischemia-reperfusion injury in humans.


Cloning of a Streptococcus mutans glucosyltransferase gene coding for insoluble glucan synthesis.
The gtfB gene coding for a glucosyltransferase (GTF) activity of Streptococcus mutans GS-5 was isolated on a 15.4-kilobase DNA fragment by using a lambda L47.1 gene library. The activity was catalyzed by gene products of 150 and 145 kilodaltons which reacted with antibodies directed against both soluble and insoluble glucan-synthesizing GTFs. The enzyme present in crude Escherichia coli extracts synthesized both soluble and insoluble glucans. The enzyme was partially purified from lysates of the lambda DS-76 clone and synthesized both types of glucans in a primer-independent fashion. In addition, the purified enzyme exhibited a pI of approximately 5.0. Southern blot analysis indicated that the cloned GTF gene represented a contiguous nucleotide sequence on the strain GS-5 chromosome. Furthermore, evidence for the existence of a distinct gene sharing partial homology with gtfB was also obtained. The gtfB gene was subcloned into plasmid pACYC184 into E. coli and exhibited GTF activity when carried on GS-5 inserts as small as 5 kilobases. The approximate location of the GTF promoter and the direction of gene transcription were also determined. The cloned enzyme was not secreted through the cytoplasmic membrane of E. coli, since most of the activity was found in the cytoplasm and, in lesser amounts, associated with the cytoplasmic membrane. The gtfB gene was insertionally inactivated by introducing a gene fragment coding for erythromycin resistance into the GTF coding region. After transformation of strain GS-5 with the altered gene, transformants defective in insoluble glucan synthesis were identified. These results indicate that the gtfB gene codes for a GTF involved in insoluble glucan synthesis in strain GS-5.


Triage tool for suspected COVID-19 patients in the emergency room: AIFELL score.
Clinical prediction scores support the assessment of patients in the emergency setting to determine the need for further diagnostic and therapeutic steps. During the current COVID-19 pandemic, physicians in emergency rooms (ER) of many hospitals have a considerably higher patient load and need to decide within a short time frame whom to hospitalize. Based on our clinical experiences in dealing with COVID-19 patients at the University Hospital in Zurich, we created a triage score with the acronym "AIFELL" consisting of clinical, radiological and laboratory findings. The score was then evaluated in a retrospective analysis of 122 consecutive patients with suspected COVID-19 from March until mid-April 2020. Descriptive statistics, Student's t-test, ANOVA and Scheffe's post-hoc analysis confirmed the diagnostic power of the score. The results suggest that the AIFELL score has potential as a triage tool in the ER setting intended to select probable COVID-19 cases for hospitalization in spontaneously presenting or referred patients with acute respiratory symptoms.


Glr, a glutamate racemase, supplies D-glutamate to both peptidoglycan synthesis and poly-gamma-glutamate production in gamma-PGA-producing Bacillus subtilis.
Poly-gamma-glutamate (gamma-PGA)-producing Bacillus subtilis contains two glutamate racemase genes, glr and yrpC, as does gamma-PGA-nonproducing B. subtilis strain 168. glr and yrpC on the chromosome of gamma-PGA-producing strain r22 were separately disrupted by means of gene replacement with an erythromycin resistance determinant. yrpC-disruption caused no effects on growth or gamma-PGA-production, whereas glr was disrupted only when an exogenous glr copy was present on a plasmid. In addition, the D-glutamate content of gamma-PGA produced by the yrpC-disruptant was the same as that produced by the parental strain r22. Glr in strain r22 is therefore responsible for the supply of D-glutamate to the synthesis of both peptidoglycan and gamma-PGA. Consistent with this idea, glr was transcribed actively during the exponential growth phase for peptidoglycan synthesis and continuously at a low, but distinct, level during the stationary phase for gamma-PGA production, whereas yrpC was transcribed at a very low level throughout growth. Phylogenetic analysis of glutamate racemases from eubacteria showed that YrpC is distinct from other glutamate racemases.


Successful treatment of refractory cutaneous infection caused by Mycobacterium marinum with a combined regimen containing amikacin.
The incidence of Mycobacterium marinum infection has been increasing. First-line antituberculous drugs and other common antibiotics are effective for most cutaneous M. marinum infections; however, treatment failure still occurs in some rare cases. We report a case of a 70-year-old man with refractory cutaneous infection caused by M. marinum. Reasons for delayed diagnosis and related factors of the refractory infection are also discussed. Samples of lesional skin were inoculated on Löwenstein-Jensen medium for acid-fast bacilli. Species of mycobacterium were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. We then carried out genotyping by using mycobacterial interspersed repetitive units and sequencing of heat shock protein 65 (hsp65) and 16S rDNA genes. Tissue cultures for acid-fast bacilli were positive. PCR-RFLP analysis and sequencing of hsp65 and 16S rDNA genes confirmed the isolated organisms to be M. marinum. Systemic therapy with rifampicin, clarithromycin, and amikacin empirically over 6 months led to complete resolution of skin lesions leaving only some residual scars. Key diagnostic elements for M. marinum infections include a high index of suspicion raised by chronic lesions, poor response to conventional treatments, and a history of fish-related exposure. Strong clinical suggestion of M. marinum infection warrants initial empirical treatment. The duration of therapy is usually several months or even longer, especially for elderly patients. Amikacin can be considered in multidrug therapy for treatment of some refractory M. marinum infections.


Chest radiographic findings in pediatric patients with intraluminal pulmonary vein stenosis.
Early recognition of pulmonary vein stenosis (PVS) is crucial for optimizing clinical outcomes. Our goal was to characterize radiographic patterns specific to pediatric patients with PVS to facilitate early detection. Pediatric patients with multivessel (≥2) intraluminal PVS were identified from a single-center registry. Initial chest radiographs were reviewed. Radiographic findings were summarized using frequencies and percentages for categorical data, and medians and ranges for continuous data. Interrater agreement was assessed using kappa statistics. Chest radiographs of 41 PVS patients were evaluated; median age at presentation 5.2 (0.5-102.6) months. Underlying congenital heart disease was present in 31 (76%), lung disease in four (10%), and neither in six (15%). Common heart diseases were hypoplastic left heart syndrome (five, 12%), totally anomalous pulmonary venous connection (nine, 22%), and heterotaxy (five, 12%). PVS was bilateral in 22 (54%), right-sided in six (14%), and left-sided in 13 (32%). All chest radiographs were abnormal. Increased interstitial opacity was present in all patients, reticular opacity in 35 (85%), and ground-glass opacity in 29 (71%). Consolidation (one, 2%), pleural effusions (four, 10%), and nodular opacities (0) were unusual. Distributional heterogeneity was common (17, 42%). Interrater agreement was generally high (kappa >0.84) except for lobe location. Findings were similar among patients with isolated PVS, PVS with congenital heart disease, and PVS with lung disease. Diagnosis of PVS should be considered in infants with increased interstitial opacity, reticular opacity, and ground-glass opacity on chest radiography, especially if findings are heterogeneous.


Cardiac adaptation to endurance exercise in rats.
Endurance exercise is widely assumed to improve cardiac function in humans. This project has determined cardiac function following endurance exercise for 6 (n = 30) or 12 (n = 25) weeks in male Wistar rats (8 weeks old). The exercise protocol was 30 min/day at 0.8 km/h for 5 days/week with an endurance test on the 6th day by running at 1.2 km/h until exhaustion. Exercise endurance increased by 318% after 6 weeks and 609% after 12 weeks. Heart weight/kg body weight increased by 10.2% after 6 weeks and 24.1% after 12 weeks. Echocardiography after 12 weeks showed increases in left ventricular internal diameter in diastole (6.39 +/- 0.32 to 7.90 +/- 0.17 mm), systolic volume (49 +/- 7 to 83 +/- 11 miccrol) and cardiac output (75 +/- 3 to 107 +/- 8 ml/min) but not left wall thickness in diastole (1.74 +/- 0.07 to 1.80 +/- 0.06 mm). Isolated Langendorff hearts from trained rats displayed decreased left ventricular myocardial stiffness (22 +/- 1.1 to 19.1 +/- 0.3) and reduced purine efflux during pacing-induced workload increases. 31P-NMR spectroscopy in isolated hearts from trained rats showed decreased PCr and PCr/ATP ratios with increased creatine, AMP and ADP concentrations. Thus, this endurance exercise protocol resulted in physiological hypertrophy while maintaining or improving cardiac function.


Host cell gene expression during human immunodeficiency virus type 1 latency and reactivation and effects of targeting genes that are differentially expressed in viral latency.
The existence of reservoirs of cells latently infected with human immunodeficiency virus (HIV) is a major obstacle to the elimination of HIV infection. We studied the changes in cellular gene expression that accompany the reactivation and completion of the lytic viral cycle in cell lines chronically infected with HIV-1. We found that several genes exhibited altered expression in the chronically infected cells compared to the uninfected parental cells prior to induction into lytic replication. A number of gene classes showed increased expression in the chronically infected cells, notably including genes encoding proteasomes, histone deacetylases, and many transcription factors. Following induction of the lytic replication cycle, we observed ordered, time-dependent changes in the cellular gene expression pattern. Approximately 1,740 genes, many of which fall into 385 known pathways, were differentially expressed (P < 0.001), indicating that completion of the HIV replication cycle is associated with distinct, temporally ordered changes in host cell gene expression. Maximum changes were observed in the early and intermediate phases of the lytic replication cycle. Since the changes in gene expression in chronically infected cells suggested that cells latently infected with HIV have a different gene expression profile than corresponding uninfected cells, we studied the expression profiles of three different chronically infected cell lines to determine whether they showed similar changes in common cellular genes and pathways. Thirty-two genes showed significant differential expression in all cell lines studied compared to their uninfected parental cell lines. Notable among them were cdc42 and lyn, which were downregulated and are required for HIV Nef binding and viral replication. Other genes previously unrelated to HIV latency or pathogenesis were also differentially expressed. To determine the effects of targeting products of the genes that were differentially expressed in latently infected cells, we treated the latently infected cells with a proteasome inhibitor, clastolactacystin-beta-lactone (CLBL), and an Egr1 activator, resveratrol. We found that treatment with CLBL and resveratrol stimulated lytic viral replication, suggesting that treatment of cells with agents that target cellular genes differentially expressed in latently infected cells can stimulate lytic replication. These findings may offer new insights into the interaction of the latently infected host cell and HIV and suggest therapeutic approaches for inhibiting HIV infection and for manipulating cells latently infected with HIV so as to trigger lytic replication.


How effective is penetrating corneal transplantation? Factors influencing long-term outcome in multivariate analysis.
In a large patient cohort, we investigated long-term corneal graft outcome, risk factors for graft failure, and whether corneal graft survival had improved over time. Records of 10,952 full-thickness corneal grafts with associated archival follow-up were examined within a prospectively-maintained, national database of 13,831 records, with follow-up extending for up to 18 years. Kaplan-Meier survival analysis was used to indicate variables of interest for Cox proportional hazards regression analysis. A model clustered by individual patient to control for inter-eye or inter-graft dependence was constructed to identify variables best predicting penetrating corneal graft failure. Probability of corneal graft survival was 0.86 at 1 year, 0.73 at 5 years, 0.62 at 10 years, and 0.55 at 15 years. Graft survival did not improve over a 15-year timeframe. Variables predicting graft failure in multivariate analysis included transplant centre, donor age, preoperative diagnosis, number of previous ipsilateral grafts, lens status, history of corneal neovascularisation, ocular inflammation or raised intraocular pressure in the grafted eye, requirement for anterior vitrectomy, graft size, early suture removal, postoperative events including graft neovascularisation, rise in intraocular pressure, and rejection episodes, type of treatment for raised intraocular pressure, and arrangements for recipient follow-up. A further 11 variables showing a significant influence on graft survival in univariate analysis were not included in the final Cox model. The long-term results of corneal transplantation are no better than for other forms of transplantation and have shown no measurable improvement over the past 15 years.


Assessing the need for Clinical Breast Examination (CBE) training: the Oregon experience.
Despite the widely held perception that CBE training has high priority among the continuing medical education (CME) needs of breast health care providers, there is actually little published information to support this notion. The authors conducted a statewide needs assessment mail survey of providers regarding a number of potential CME needs, including CBE training. Of the 4,179 surveys from the single mailing, 1,427 were returned (34% response rate). Six categories of provider types responded; 51% were physicians and 23% were nurse practitioners. Fifty-nine percent of the respondents were female; 96% felt that routine CBE was an important or very important part of providing breast care. Although 79% of all respondents performed CBE at least weekly and 41% performed more than ten CBEs/week, 80% were interested in receiving some form of CME regarding CBE, and 79% of those who performed CBE at least weekly were interested in receiving skill-based CBE training. Despite the respondent bias inherent in survey studies, it can be concluded that there is indeed a CME need for CBE training, even among providers who perform CBE frequently. Based on these findings the authors are implementing a statewide CME program of CBE training.


Relapse versus reinfection with Clostridium difficile.
Relapse of Clostridium difficile-associated diarrhoea occurs in 15-20% of patients; however, whether relapse is due to an endogenous source of the organism or reinfection from the environment remains unclear. Restriction enzyme analysis (REA) of chromosomal DNA was used to type multiple isolates from ten patients who had experienced apparent relapses. More than half the relapses were due to infection with a new strain of C. difficile. The remaining patients were infected with the same strain, but whether this strain was acquired from the environment or from endogenous sources could not be determined. Relapses with a different strain of C. difficile could occur if an individual harboured more than one strain in their gastrointestinal tract. To investigate this possibility ten other patients were assessed for carriage of multiple strains. Ten colonies from a primary culture plate from each patient were typed by REA and tested for their ability to produce cytotoxin. All isolates from the same patient were identical by both methods, indicating that multiple carriage of strains may be a rare event.


Fossil spiders.
Over the last three decades, the fossil record of spiders has increased from being previously biased towards Tertiary ambers and a few dubious earlier records, to one which reveals a much greater diversity in the Mesozoic, with many of the modern families present in that era, and with clearer evidence of the evolutionary history of the group. We here record the history of palaeoarachnology and the major breakthroughs which form the basis of studies on fossil spiders. Understanding the preservation and taphonomic history of spider fossils is crucial to interpretation of fossil spider morphology. We also review the more recent descriptions of fossil spiders and the effect these discoveries have had on the phylogenetic tree of spiders. We discuss some features of the evolutionary history of spiders and present ideas for future work.


Real-Time Impedance Monitoring During Electroporation Processes in Vegetal Tissue Using a High-Performance Generator.
Classical application of electroporation is carried out by using fixed protocols that do not clearly assure the complete ablation of the desired tissue. Nowadays, new methods that pursue the control of the treatment by studying the change in impedance during the applied pulses as a function of the electric field are being developed. These types of control seek to carry out the treatment in the fastest way, decreasing undesired effects and treatment time while ensuring the proper tumour ablation. The objective of this research is to determine the state of the treatment by continuously monitoring the impedance by using a novel versatile high-voltage generator and sensor system. To study the impedance dynamics in real time, the use of pulses of reduced voltage, below the threshold of reversible electroporation, is tested to characterise the state-of-the-treatment without interfering with it. With this purpose, a generator that provides both low voltage for sense tissue changes and high voltage for irreversible electroporation (IRE) was developed. In conclusion, the characterisation of the effects of electroporation in vegetal tissue, combined with the real-time monitoring of the state-of-the-treatment, will enable the provision of safer and more effective treatments.


Disease knowledge, perceived risk, and health behavior engagement among adolescents and adults with congenital heart disease.
Survivors of congenital heart disease (CHD) are at risk for life-threatening complications as they age. This study aimed to examine the association of knowledge of future health risks, perceived risk, and health behaviors among adolescents and adults with CHD. CHD survivors (N = 200, ages 15-39; 23% simple, 44% moderate, 33% complex lesions) completed measures of risk knowledge accuracy and perceived risk for developing complications, and reported physical activity and saturated fat intake. CHD survivors reported poor risk knowledge and consuming high-fat diets. Adolescents reported more physical activity than young adults. Greater risk knowledge was associated with lower fat intake, and participants who exercised more expected fewer future complications, and this difference remained statistically significant when accounting for education and age. CHD survivors, regardless of age, have poor risk knowledge and diets. Survivors may benefit from emphasis on future health risks and health behaviors from both pediatric and adult providers.


Distinct GluN1 and GluN2 Structural Determinants for Subunit-Selective Positive Allosteric Modulation of N-Methyl-d-aspartate Receptors.
N-Methyl-d-aspartate receptors (NMDARs) are ionotropic ligand-gated glutamate receptors that mediate fast excitatory synaptic transmission in the central nervous system (CNS). Several neurological disorders may involve NMDAR hypofunction, which has driven therapeutic interest in positive allosteric modulators (PAMs) of NMDAR function. Here we describe modest changes to the tetrahydroisoquinoline scaffold of GluN2C/GluN2D-selective PAMs that expands activity to include GluN2A- and GluN2B-containing recombinant and synaptic NMDARs. These new analogues are distinct from GluN2C/GluN2D-selective compounds like (+)-(3-chlorophenyl)(6,7-dimethoxy-1-((4-methoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone (CIQ) by virtue of their subunit selectivity, molecular determinants of action, and allosteric regulation of agonist potency. The (S)-enantiomers of two analogues (EU1180-55, EU1180-154) showed activity at NMDARs containing all subunits (GluN2A, GluN2B, GluN2C, GluN2D), whereas the (R)-enantiomers were primarily active at GluN2C- and GluN2D-containing NMDARs. Determination of the actions of enantiomers on triheteromeric receptors confirms their unique pharmacology, with greater activity of (S) enantiomers at GluN2A/GluN2D and GluN2B/GluN2D subunit combinations than (R) enantiomers. Evaluation of the (S)-EU1180-55 and EU1180-154 response of chimeric kainate/NMDA receptors revealed structural determinants of action within the pore-forming region and associated linkers. Scanning mutagenesis identified structural determinants within the GluN1 pre-M1 and M1 regions that alter the activity of (S)-EU1180-55 but not (R)-EU1180-55. By contrast, mutations in pre-M1 and M1 regions of GluN2D perturb the actions of only the (R)-EU1180-55 but not the (S) enantiomer. Molecular modeling supports the idea that the (S) and (R) enantiomers interact distinctly with GluN1 and GluN2 pre-M1 regions, suggesting that two distinct sites exist for these NMDAR PAMs, each of which has different functional effects.


Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay.
The RBD (receptor binding domain) of the SARS-CoV-2 virus S (spike) protein mediates viral cell attachment and serves as a promising target for therapeutics development. Mutations on the S-RBD may alter its affinity to the cell receptor and affect the potency of vaccines and antibodies. Here we used an in silico approach to predict how mutations on RBD affect its binding affinity to hACE2 (human angiotensin-converting enzyme2). The effect of all single point mutations on the interface was predicted. SPR assay results show that 6 out of 9 selected mutations can strengthen binding affinity. Our prediction has reasonable agreement with the previous deep mutational scan results and recently reported mutants. Our work demonstrated the in silico method as a powerful tool to forecast more powerful virus mutants, which will significantly benefit the development of broadly neutralizing vaccine and antibody.