Sarin causes altered time course of mRNA expression of alpha tubulin in the central nervous system of rats.
Sarin induced neurotoxicity is suspected to be one of the key factors responsible for Gulf-war syndrome. We studied the effect of a single (50 microg/kg/i.m) dose of sarin (0.5 x LD50) on the mRNA expression of alpha tubulin in the central nervous system (CNS) of rats which were sacrificed at different time points i.e. 1 and 2 hrs, as well as, 1, 3 and 7 days post-treatment. Northern data collected from CNS regions indicate differential, spatial, and temporal regulation of alpha tubulin mRNA levels. Immediate induction and persistence of alpha tubulin transcripts in sarin-treated CNS suggest that sarin-induced neurotoxicity is in part mediated by the altered expression of cytoskeletal genes which may be regulated at multiple levels.


DNA structural dynamics: longitudinal breathing as a possible mechanism for the B in equilibrium Z transition.
The transition from B-DNA to Z-DNA not only requires a change in the helix architecture from a right-handed to a left-handed form, but also requires that all of the base pairs be flipped over. A transition mechanism is proposed in which the base pairs flip over one at a time while keeping the Watson-Crick hydrogen bonds intact. The two base pairs on either side of the pair that turns over form a kind of dynamic sandwich around it, and the flip takes place in a cavity that is formed when the distance between them is increased from about 7A in the intact helix to about 14A in the transition state. Since the transition occurs in two steps (formation of the cavity, followed by the base pair flip) and since the cavity propagates down the helix after the base pair is turned over, the mechanism accounts for the cooperativity of the B in equilibrium Z transition.


EDUCATIONAL SERIES IN CONGENITAL HEART DISEASE: Cardiovascular MRI and CT in congenital heart disease.
Cardiovascular MRI and CT are useful imaging modalities complimentary to echocardiography. This review article describes the common indications and consideration for the use of MRI and CT in the management of congenital heart disease.


Acute ischemic syndromes.
The diagnosis and treatment of patients with acute manifestations of ischemic heart disease are major public health issues. This article reviews the current state of knowledge about the problem of acute ischemic syndromes, the events leading to clinical manifestations, the key elements of the diagnosis, the therapies that can affect outcome, and the organization of systems to deal with this problem in a cost-effective manner.


Psychostimulant and nootropic effect of major and trace element composition.
We studied the effect of a composition of major and trace elements including calcium chloride, sodium chloride, iron (II) sulfate, zinc sulfate, chromium (III) chloride, and potassium bromide on orientation and exploratory behavior and conditioned response of animals in the open field test and conditioned drinking response in a multiple T-maze with three junctions. The test compound exhibited psychostimulant and nootropic activities.


Expression of genes for thioredoxin 1 and thioredoxin 2 in multidrug resistance ovarian carcinoma cells SKVLB.
The expression of genes for thioredoxin isoforms Trx1 and Trx2 was studied in sensitive SKOV-3 and resistant SKVLB human ovarian carcinoma cells. The development of doxorubicin resistance was accompanied by a significant increase in the expression of TRX1 gene and less pronounced increase in TRX2 gene expression.


Cytochalasin B and the kinetics of inhibition of biological transport: a case of asymmetric binding to the glucose carrier.
Cytochalasin B inhibits glucose transport in human erythrocytes by competing with glucose for the carrier on the inner surface of the cell membrane, but there is no cytochalasin site associated with the outware-facing form of the carrier. Such asymmetry may be demonstrated by zero trans exit and entry experiments, whereas Sen-Widdas exit experiments are not easily interpretable. The orientation of the transport system appears to be reversed in certain other cell types: chich embryo fibroblasts, Novikoff hepatoma cells and HeLa cells. Here the cytochalasin site is present in the external but not internal carrier form.


Anticonvulsant Effectiveness and Neurotoxicity Profile of 4-butyl-5-[(4-chloro-2-methylphenoxy)methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (TPL-16) in Mice.
Protective (antiseizure) effects of 4-butyl-5-[(4-chloro-2-methylphenoxy)-methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (TPL-16) and acute neurotoxic effects were determined in the tonic-clonic seizure model and rotarod test in mice. The interaction profile of four classic antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) with TPL-16 was also determined in the tonic-clonic seizure model in mice. The protective effects of TPL-16 from tonic-clonic seizures (as ED50 values) and acute neurotoxic effects of TPL-16 (as TD50 values) were determined in 4 pretreatment times (15, 30, 60 and 120 min after its i.p. administration), in adult male albino Swiss mice. The interaction profile of TPL-16 with carbamazepine, phenobarbital, phenytoin and valproate in the tonic-clonic seizure model was determined with isobolographic analysis. Total concentrations of carbamazepine, phenobarbital, phenytoin and valproate were measured in the mouse brain homogenates. The candidate for novel antiepileptic drug (TPL-16) administered separately 15 min before experiments, has a beneficial profile with protective index (as ratio of TD50 and ED50 values) amounting to 5.58. The combination of TPL-16 with valproate produced synergistic interaction in the tonic-clonic seizure model in mice. The combinations of TPL-16 with carbamazepine, phenobarbital and phenytoin produced additive interaction in terms of protection from tonic-clonic seizures in mice. None of the total brain concentrations of classic AEDs were changed significantly after TPL-16 administration in mice. Synergistic interaction for TPL-16 with valproate and the additive interaction for TPL-16 with carbamazepine, phenobarbital and phenytoin in the tonic-clonic seizures in mice allows for recommending TPL-16 as the promising drug for further experimental and clinical testing.


In vitro microelectrode study of neuromuscular transmission in a case of botulism.
We performed in vitro microelectrode studies in the anconeus muscle biopsy of a 6-week-old infant intoxicated with Clostridium botulinum toxin B. The most striking abnormalities were the severe reduction of the endplate potential (EPP) quantal content and the marked variability of EPP latencies. The increased variability was often limited to a "single quantum" component of the EPP. Neither the amplitudes nor the frequencies of spontaneous miniature endplate potentials (MEEPs) were decreased. However, there was a wide range of amplitudes and frequencies of MEPPs. This unique combination of electrophysiologic findings indicates a severe presynaptic failure of neuromuscular transmission, which appears to result from an impairment of the process of synaptic vesicle release taking place after the stimulus induced influx of calcium into the motor nerve terminals.


Mediators of clinical judgment: an exploration of the effect of therapists' locus of control on clinical expectations.
In this study, written case vignettes that manipulated locus of control symptoms, class, and sex of the clients were presented to 174 Australian clinical psychologists. Therapists' expectations of success with clients presented in the vignettes were found to be primarily a function of the interaction between the therapist's and the hypothetical client's locus of control. In addition, some variance was explained by the symptoms of clients in the vignettes. Clients with mild problems were generally rated more favorably than clients with severe problems.


Rehabilitation of avulsion fracture of the tibial tuberosity following Osgood-Schlatter disease.
A sixteen-year-old boy suffered from sharp pain in the knee during a jump while playing basketball. He had a positive history of Osgood Schlatter disease. Radiographic evaluation demonstrated an avulsion fracture of the tibial tuberosity Type III according to the classification of Watson-Jones. Rehabilitation after avulsion fracture of the tibial tuberosity is an important consideration for this relatively uncommon adolescent injury. In such avulsion fractures, landing on the ground with the knee fully extended after a jump is the most likely cause. This case report reviews the rehabilitation program, and selected functional outcome measures after rehabilitation are reported. The patient returned to sporting activity after 12 months.


Scientists May Approach the Bench.
NASA science is lightening up and embracing microgravity research on the International Space Station, reports Nature in this week's lead article. Science's lead story covers a group of litigious tissue donors who are trying to recover control of their genes.


Phosphorylation of the aggregate-forming protein alpha-synuclein on serine-129 inhibits its DNA-bending properties.
Alpha-synuclein (aSyn) is a vertebrate protein, normally found within the presynaptic nerve terminal and nucleus, which is known to form somatic and neuritic aggregates in certain neurodegenerative diseases. Disease-associated aggregates of aSyn are heavily phosphorylated at serine-129 (pSyn), while normal aSyn protein is not. Within the nucleus, aSyn can directly bind DNA, but the mechanism of binding and the potential modulatory roles of phosphorylation are poorly understood. Here we demonstrate using a combination of electrophoretic mobility shift assay and atomic force microscopy approaches that both aSyn and pSyn can bind DNA within the major groove, in a DNA length-dependent manner and with little specificity for DNA sequence. Our data are consistent with a model in which multiple aSyn molecules bind a single 300 base pair (bp) DNA molecule in such a way that stabilizes the DNA in a bent conformation. We propose that serine-129 phosphorylation decreases the ability of aSyn to both bind and bend DNA, as aSyn binds 304 bp circular DNA forced into a bent shape, but pSyn does not. Two aSyn paralogs, beta- and gamma-synuclein, also interact with DNA differently than aSyn, and do not stabilize similar DNA conformations. Our work suggests that reductions in aSyn's ability to bind and bend DNA induced by serine-129 phosphorylation may be important for modulating aSyn's known roles in DNA metabolism, including the regulation of transcription and DNA repair.


A 45-year follow-up study of adolescent schizophrenia. Part I: Premorbid values of psychological and relational indicators in the context of illness course and long-term social functioning of patients.
Research on predictors of adolescent schizophrenia, especially those based on long-term follow-up studies, is rare in the literature. In our analysis, we examine the relationship between the premorbid functioning of the respondents and clinical and social indicators of the illness course. 69 patients at the average age of 16 years (time point 0), hospitalized due to schizophrenia (retrospectively re-diagnosed according to ICD-10 criteria) and re-examined 5 years later (time point 1 - personal examination of 41 individuals), were re-evaluated for clinical and social parameters 45 yearsafter their initial hospitalization (time point 2 -personal examination of 21 individuals). Premorbid indicators of mood, life drive, emotional expression, level of social withdrawal, intelligence, anxiety, development of sexual and aggressive drive, and family and extra-family relational life revealed numerous and various correlations with both the symptomatic picture and clinical course of schizophrenia as well as distant social functioning of the subjects. Variables of the greatest prognostic value were: the emotional attitude of "moving away from" people and the world, and rich relational life outside the family of origin. These variables revealed opposite correlations, especially with the severity of negative symptoms, the level of late insight and regression, the quality of professional life and GAF scores, with the correlations of rich relational lifeto be assessed as positive and the correlations of attitude of "moving away from" as negative. The harmonious development of drive as well as high intelligence also proved to be significant. The correlations of both of these variables have proved beneficial both in clinical and social terms. The so-called premorbid personality described by several indicators turns out to be an important prognostic factor in juvenile schizophrenia.


[Nazi action T4 euthanasia programme: historical research, individual life stories and the culture of remembrance].
The psychiatric patients killed under the disguise of euthanasia during World War II belong to the group of victims which are often forgotten in public remembrance. For German and Austrian psychiatry it is important to include them into the memory of the discipline as well as into European remembrance of the victims of Nazi annihilation policy. The patient files of the victims enable us to reconstruct the criterion of economic usefulness for deciding about life or death. But above all the files are the basis on which the suffering and the life histories of the patients can be told.


Corrigendum: The Aging Slopes of Brain Structures Vary by Ethnicity and Sex: Evidence From a Large Magnetic Resonance Imaging Dataset From a Single Scanner of Cognitively Healthy Elderly People in Korea.
[This corrects the article DOI: 10.3389/fnagi.2020.00233.].


Yan-Hou-Qing formula attenuates ammonia-induced acute pharyngitis in rats via inhibition of NF-κB and COX-2.
Yan Hou Qing (YHQ) is a Chinese medicinal formula designed to alleviate sore throat symptoms, but underlying mechanism of YHQ treatment for pharyngitis is poorly defined up to now. In this study, the modulation of YHQ on pharyngitis is investigated in ammonia-induced acute pharyngitis rat models. After treatment with YHQ or dexamethasone respectively for five consecutive days, all rats were sacrificed for biomolecular and histopathologic study. Protein expressions of MAPKs, NF-κB, COX-2 and 5-LOX in pharyngitis tissue were evaluated by western blot analysis and the levels of TNF-α, IL-6, prostaglandin (PG) E2, leukotrienes (LT)-B4 and LT-D4 in pharyngeal tissue were measured via ELISA assay. Evans blue (EB) dye exudation test was performed parallelly to assess the integrity of pharyngeal tissue. Compared with normal control group, EB dye exudation, and inflammatory cytokines in the model group were significantly increased, and the pharynx tissue was obviously infiltrated by inflammatory cells. YHQ treatment improved the inflammatory infiltrate in pharyngeal tissue, and reduced EB dye exudation in AP rat models. The up-regulated TNF-α and IL-6 in pharyngeal tissue of AP were significantly reduced by YHQ through inhibition of phosphorylation of p38, Erk and NF-κB. YHQ treatment also reversed the increased level of PGE2 through down-regulation of COX-2. YHQ formula attenuated the pharyngitis related symptoms via suppression of COX-2 and phosphorylation of p38, Erk and NF-κB (p65).


Evaluation of short-term face rejuvenation effects of non-ablative bipolar radiofrequency treatment performed by Med-RF© device.
Skin laxity and wrinkling are common signs of the aging process. This physiological condition of the skin is often accompanied by psychological and social concerns, especially for females, entailing considerable expenses for cosmetics and pharmaceuticals to cease or slow down its advancement. The objective of this study was to evaluate the short-term impact of a new non-ablative radiofrequency device available in the skin face cosmetic field. A randomized study was run on 62 healthy subjects with normal-age related-grade skin laxity, subdivided into two groups. Group 1 received one treatment with Modula RF device (Wavemed, San Cesareo RM, Italy) over the whole face surface. Group 2 received three monthly treatments. Clinical improvements of the exposed areas were detected by measuring skin parameters, such as total water content, elasticity, and sebum levels at baseline and 1 h after the treatment. Data showed significant effects of Med-RF treatment on skin hydration (p < 0.001), skin elasticity (p < 0.0001), and sebum (p = 0.0009). Moreover, a negative linear correlation was obtained between women's age and hydration. In conclusion, the results of this study suggest that radiofrequency significantly improves the subjective and objective judgment of patients and doctors, supported by the positive results obtained on the skin quality parameters evaluated. These results confirm that Med-RF technology represents an important tool to achieve face rejuvenation in the field of non-invasive procedures.


[Results of the Massive Open Online Course (MOOC) on cancer diagnosis and evaluation of its impact on the perception of the pathology specialty].
The Massive Open Online Course (or MOOC) "Diagnostic Strategies Cancers", was hosted in autumn 2016 on the platform "France Université Numérique" and had two levels of learners: students in the field of health and biology and the general public. Of the 5285 learners in 81 different countries, 1237 (23%) were successfully certified. This MOOC was also integrated into the teaching program of medical students of Paris Diderot University and Paris 13 University. Using anonymous questionnaires before and after MOOC, it has been shown that pathology is less known than other medical specialties. Participation in this MOOC led to a marked improvement in participants' knowledge of the place and role of the pathologist in the diagnosis of cancers. Regarding the students who have followed the MOOC as part of their university course, their comments were very positive, but it is necessary to make substantial adjustments in the amounts and contents of the campus-based courses.


ONTOGENY AND PHYLOGENETIC SYSTEMATICS.
Abstract- Dedifferentiation, paedomorphosis, and the insertion and deletion of developmental stages make it impossible to deduce the genealogical hierarchy from only ontogenetic transformation series. Like the outgroup criterion, ontogenetic character precedence is not theory-neutral and to use it to deduce genealogy requires certain assumptions. If scientists are going to use logically unbeatable theories about the world, they might as well give up natural science and take up religion (Lewontin, 1972: 181).


A dual-response fluorescent probe for discriminative sensing of hydrazine and bisulfite as well as intracellular imaging with different emission.
Bisulfite and hydrazine are harmful to the environment safety and human health. Therefore, it is of great value to develop a smart fluorescent probe with high selectivity for detection of bisulfite and hydrazine. In our report, a dual-response fluorescent probe EDBI with high selectivity, rapid response, and low detection limit for discriminative determination HSO3- and N2H4 was exploited. The probe EDBI is capable of distinctive sensing HSO3- and N2H4 based on nucleophilic addition reactions by taking advantage of ratiometric fluorescence and fluorescence "on-off" mode, respectively. The dual-responses behaviors of probe EDBI toward HSO3- and N2H4 were attribute to different reaction sites, which it has been confirmed by HRMS. More importantly, cytotoxicity experiment authenticated that probe possesses low toxicity and good penetration. The probe EDBI with excellent performance, it was successfully employed to distinguishable sense HSO3- and N2H4 in living cells by diverse channel patterns. Therefore, this simple dual-response fluorescence probe is expected to be used for real-time monitoring bisulfite and hydrazine in biological samples.


A probabilistic topic model for clinical risk stratification from electronic health records.
Risk stratification aims to provide physicians with the accurate assessment of a patient's clinical risk such that an individualized prevention or management strategy can be developed and delivered. Existing risk stratification techniques mainly focus on predicting the overall risk of an individual patient in a supervised manner, and, at the cohort level, often offer little insight beyond a flat score-based segmentation from the labeled clinical dataset. To this end, in this paper, we propose a new approach for risk stratification by exploring a large volume of electronic health records (EHRs) in an unsupervised fashion. Along this line, this paper proposes a novel probabilistic topic modeling framework called probabilistic risk stratification model (PRSM) based on Latent Dirichlet Allocation (LDA). The proposed PRSM recognizes a patient clinical state as a probabilistic combination of latent sub-profiles, and generates sub-profile-specific risk tiers of patients from their EHRs in a fully unsupervised fashion. The achieved stratification results can be easily recognized as high-, medium- and low-risk, respectively. In addition, we present an extension of PRSM, called weakly supervised PRSM (WS-PRSM) by incorporating minimum prior information into the model, in order to improve the risk stratification accuracy, and to make our models highly portable to risk stratification tasks of various diseases. We verify the effectiveness of the proposed approach on a clinical dataset containing 3463 coronary heart disease (CHD) patient instances. Both PRSM and WS-PRSM were compared with two established supervised risk stratification algorithms, i.e., logistic regression and support vector machine, and showed the effectiveness of our models in risk stratification of CHD in terms of the Area Under the receiver operating characteristic Curve (AUC) analysis. As well, in comparison with PRSM, WS-PRSM has over 2% performance gain, on the experimental dataset, demonstrating that incorporating risk scoring knowledge as prior information can improve the performance in risk stratification. Experimental results reveal that our models achieve competitive performance in risk stratification in comparison with existing supervised approaches. In addition, the unsupervised nature of our models makes them highly portable to the risk stratification tasks of various diseases. Moreover, patient sub-profiles and sub-profile-specific risk tiers generated by our models are coherent and informative, and provide significant potential to be explored for the further tasks, such as patient cohort analysis. We hypothesize that the proposed framework can readily meet the demand for risk stratification from a large volume of EHRs in an open-ended fashion.


Management of postmenopausal bleeding to prevent endometrial cancer.
The primary goal in management of postmenopausal bleeding is to insure that no malignancy is present. In this study of 3,682 climacteric women, 340 patients (9.2%) presented with postmenopausal bleeding during an 18-mth period. The pathology at curettage was reported as normal endometrium in 33.8%, atrophic endometrium in 24.7%, and hyperplasia in 39.1%. Adenocarcinoma of the endometrium was diagnosed in only 5 patients (1.5%), a reduction from 3.0% found in a previous study performed in 1972-1973. The second goal in management of postmenopausal bleeding is to identify and treat those patients with endometrial hyperplasia since this is a precancerous lesion. Cyclic progestogens were given to 105 of 133 women with hyperplasia of the endometrium for 3-6 mth and curettage repeated. The hyperplasia reverted to normal endometrium in 101 of the 105 patients (96.2%). In those 4 women with persistent hyperplasia after progestogen therapy, a hysterectomy was performed. Hysterectomy was the primary therapy for 20 women with hyperplasia because of associated findings such as leiomyomata uteri. The incidence of curettage was highest in the untreated women (23.2%), lowest in the estrogen-progestogen users (3.9%) and indicated in 14.2% of those patients receiving estrogens alone.


MEHP-induced oxidative DNA damage and apoptosis in HepG2 cells correlates with p53-mediated mitochondria-dependent signaling pathway.
In the present study, the effects of MEHP on human hepatocellular liver carcinoma HepG2 cells were investigated. The results showed that MEHP-induced oxidative DNA damage in the treatment groups (≥ 25.00 μM) at 24h after treatment and in the 100.00 μM treatment group at 36 h after treatment (p < 0.05 or p < 0.01). At 36 h after treatment, MEHP at higher concentrations (≥ 25.00 μM) resulted in a decrease in ATP level, and an increase in the protein levels of cytochrome c and Smac/DIABLO in the cytosol as well as the percentage of apoptotic cells. The activation of caspase-9 and -3 and the expression of the selected apoptosis-related proteins, p53, PUMA, NOXA, Bax and Bcl-2 were also induced. Furthermore, vitamin C, a scavenger of reactive oxygen species, attenuated MEHP-induced apoptosis. These findings indicated that MEHP induced oxidative DNA damage and apoptosis in HepG2 cells, and p53 and its downstream proteins were involved in mitochondria- and caspase-mediated apoptosis induced by MEHP.


Maintaining sagittal plane balance compromises frontal plane balance during reactive stepping in people post-stroke.
Maintaining balance in response to perturbations during walking often requires the use of corrective responses to keep the center of mass within the base of support. The relationship between the center of mass and base of support is often quantified using the margin of stability. Although people post-stroke increase the margin of stability following perturbations, control deficits may lead to asymmetries in regulation of margins of stability, which may also cause maladaptive coupling between the sagittal and frontal planes during balance-correcting responses. We assessed how paretic and non-paretic margins of stability are controlled during recovery from forward perturbations and determined how stroke-related impairments influence the coupling between the anteroposterior and mediolateral margins of stability. Twenty-one participants with post-stroke hemiparesis walked on a treadmill while receiving slip-like perturbations on both limbs at foot-strike. We assessed anteroposterior and mediolateral margins of stability before perturbations and during perturbation recovery. Participants walked with smaller anteroposterior and larger mediolateral margins of stability on the paretic versus non-paretic sides. When responding to perturbations, participants increased the anteroposterior margin of stability bilaterally by extending the base of support and reducing the excursion of the extrapolated center of mass. The anteroposterior and mediolateral margins of stability in the paretic limb negatively covaried during reactive steps such that increases in anteroposterior were associated with reductions in mediolateral margins of stability. Balance training interventions to reduce fall risk post-stroke may benefit from incorporating strategies to reduce maladaptive coupling of frontal and sagittal plane stability.


Early spinal cord pseudoatrophy in interferon-beta-treated multiple sclerosis.
Brain pseudoatrophy has been shown to play a pivotal role in the interpretation of brain atrophy measures during the first year of disease-modifying therapy in multiple sclerosis. Whether pseudoatrophy also affects the spinal cord remains unclear. The aim of this study was to analyze the extent of pseudoatrophy in the upper spinal cord during the first 2 years after therapy initiation and compare this to the brain. A total of 129 patients from a prospective longitudinal multicentric national cohort study for whom magnetic resonance imaging scans at baseline, 12 months, and 24 months were available were selected for brain and spinal cord volume quantification. Annual percentage brain volume and cord area change were calculated using SIENA (Structural Image Evaluation of Normalized Atrophy) and NeuroQLab, respectively. Linear mixed model analyses were performed to compare patients on interferon-beta therapy (n = 84) and untreated patients (n = 45). Patients treated with interferon-beta demonstrated accelerated annual percentage brain volume and cervical cord area change in the first year after treatment initiation, whereas atrophy rates stabilized to a similar and not significantly different level compared to untreated patients during the second year. These results suggest that pseudoatrophy occurs not only in the brain, but also in the spinal cord during the first year of interferon-beta treatment.


Dowsing can be interfered with by radio frequency radiation.
The soil radiation, watercourses and ores have been located for centuries by sensitive persons, dowsers. An ideomotoric explanation of the dowsing reaction, with no physical interaction, has been accepted. Our present re-analyses of some such results have shown, that there could be a physical phenomenon connecting the human reactions in field experiments, where the test subjects walked or were sitting in a slow-moving car, with the windows covered, and a dowsing rod in their hands was recorded. The correlations between the reaction points by test subjects in the moving car and the points by walking along the same path were highly significant. The correlation was not seen in all test locations. The distance between the test location and the radio tower, and the incidence angle of the transmitted radio wave, possibly had an effect on results. We hypothesize that the experiments carried out in the 20th century were interfered with by man-made radio frequency radiation, mainly FM radio and TV broadcasting, as test subjects' bodies absorbed the radio waves and unconscious hand movement reactions took place following the standing waves or intensity variations due to multipath propagation.


Downstream consequences of moral distress in COVID-19 frontline healthcare workers: Longitudinal associations with moral injury-related guilt.
To examine the longitudinal associations between dimensions of COVID-19 pandemic-related moral distress (MD) and moral injury (MI)-related guilt in a large sample of frontline COVID-19 healthcare workers (FHCWs). Data from a diverse occupational cohort of 786 COVID-19 FHCWs were collected during the initial peak of the COVID-19 pandemic in New York City and again 7 months later. Baseline MD and MI-related guilt at follow-up were assessed in three domains: family-, work-, and infection-related. Social support was evaluated as a potential moderator of associations between MD and MI-related guilt. A total of 66.8% of FHCWs reported moderate-or-greater levels of MI-related guilt, the most prevalent of which were family (59.9%) or work-related (29.4%). MD was robustly predictive of guilt in a domain-specific manner. Further, among FHCWs with high levels of work-related MD, those with greater perceptions of supervisor support were less likely to develop work-related guilt 7 months later. MD was found to be highly prevalent in FHCWs during the initial wave of the COVID-19 pandemic and was linked to the development of MI-related guilt over time. Prevention and early intervention efforts to mitigate MD and bolster supervisor support may help reduce risk for MI-related guilt in this population.


Large scale three-dimensional reconstruction of an entire Caenorhabditis elegans larva using AutoCUTS-SEM.
Large scale, high resolution three dimensional (3D) ultrastructural reconstruction of cells and tissues has become increasingly important to our understanding of complex biological systems. There have been a few partial 3D ultra-structures of Caenorhabditis elegans (C. elegans) reported, however 3D reconstruction of a whole nematode has never been achieved. Here, we independently developed a technique called automatic collector of ultrathin sections scanning electron microscopy and using this methodology, generated a 3D reconstruction of an entire C. elegans larva with 100 nm axial and 15 nm lateral resolution. Compared to the current available ATUM (automated tape-collecting ultramicrotome) technique, our work provides another alternative complete solution that can be applied to obtain large scale 3D ultrastructure of tissues. Our workflow includes an automated hardware system for high throughput serial section collection, a software package for automatic SEM imaging, and an image reconstruction program. These combined techniques can now be used together to rapidly provide access to understand the anatomy of the whole nematodes.


Tailbiter: a new amide foldamer.
Hydrogen bond directed folding of a synthetic polyamide was studied in chloroform solution, and the three-dimensional structure of the foldamer determined using 1H NMR chemical shifts.


Fetal head-down posture may explain the rapid brain evolution in humans and other primates: An interpretative review.
Evolutionary cerebrovascular consequences of upside-down postural verticality of the anthropoid fetus have been largely overlooked in the literature. This working hypothesis-based report provides a literature interpretation from an aspect that the rapid evolution of the human brain has been promoted by fetal head-down position due to maternal upright and semi-upright posture. Habitual vertical torso posture is a feature not only of humans, but also of monkeys and non-human apes that spend considerable time in a sitting position. Consequently, the head-down position of the fetus may have caused physiological craniovascular hypertension that stimulated expansion of the intracranial vessels and acted as an epigenetic physiological stress, which enhanced neurogenesis and eventually, along with other selective pressures, led to the progressive growth of the anthropoid brain and its organization. This article collaterally opens a new insight into the conundrum of high cephalopelvic proportions (i.e., the tight fit between the pelvic birth canal and fetal head) in phylogenetically distant lineages of monkeys, lesser apes, and humans. Low cephalopelvic proportions in non-human great apes could be accounted for by their energetically efficient horizontal nest-sleeping and consequently by their larger body mass compared to monkeys and lesser apes that sleep upright. One can further hypothesize that brain size varies in anthropoids according to the degree of exposure of the fetus to postural verticality. The supporting evidence for this postulation includes a finding that in fossil hominins cerebral blood flow rate increased faster than brain volume. This testable hypothesis opens a perspective for research on fetal postural cerebral hemodynamics.


The experiences of health-care providers during the COVID-19 crisis in China: a qualitative study.
In the early stages of the outbreak of coronavirus disease 2019 (COVID-19) in Hubei, China, the local health-care system was overwhelmed. Physicians and nurses who had no infectious disease expertise were recruited to provide care to patients with COVID-19. To our knowledge, no studies on their experiences of combating COVID-19 have been published. We aimed to describe the experiences of these health-care providers in the early stages of the outbreak. We did a qualitative study using an empirical phenomenological approach. Nurses and physicians were recruited from five COVID-19-designated hospitals in Hubei province using purposive and snowball sampling. They participated in semi-structured, in-depth interviews by telephone from Feb 10 to Feb 15, 2020. Interviews were transcribed verbatim and analysed using Haase's adaptation of Colaizzi's phenomenological method. We recruited nine nurses and four physicians. Three theme categories emerged from data analysis. The first was "being fully responsible for patients' wellbeing-'this is my duty'". Health-care providers volunteered and tried their best to provide care for patients. Nurses had a crucial role in providing intensive care and assisting with activities of daily living. The second category was "challenges of working on COVID-19 wards". Health-care providers were challenged by working in a totally new context, exhaustion due to heavy workloads and protective gear, the fear of becoming infected and infecting others, feeling powerless to handle patients' conditions, and managing relationships in this stressful situation. The third category was "resilience amid challenges". Health-care providers identified many sources of social support and used self-management strategies to cope with the situation. They also achieved transcendence from this unique experience. The intensive work drained health-care providers physically and emotionally. Health-care providers showed their resilience and the spirit of professional dedication to overcome difficulties. Comprehensive support should be provided to safeguard the wellbeing of health-care providers. Regular and intensive training for all health-care providers is necessary to promote preparedness and efficacy in crisis management. National Key R&D Program of China, Project of Humanities and Social Sciences of the Ministry of Education in China.


[Bone inclusion and ectopia of a superior incisor. Clinical case].
A case of inclusion and ectopia of a superior incisor resolved with the aid of a removable apparatus in reported.


A Fish-Based Index of Biotic Integrity for the Assessment of Streams Located in a Sugarcane-Dominated Landscape in Southeastern Brazil.
A multimetric, fish-based Index of Biotic Integrity (IBI) was developed and tested to assess the ecological status of streams with different riparian conditions in the Piracicaba River Basin. Nine streams with three categories of riparian zone preservation were selected: native forest (NF) with preserved forest, secondary forest (SF) with forest in an advanced state of regeneration and surrounded by sugarcane plantations, and sugarcane (SC) without riparian vegetation and surrounded by SC crops. A continuous scoring system was employed, and candidate metrics were tested for range, responsiveness, and redundancy, resulting in the selection of eight metrics to compose the index. The final IBI score was positively correlated with an Environmental Index both in the dry (Spearman's rho = 0.76; P = 0.01) and rainy seasons (Spearman's rho = 0.66; P = 0.04), suggesting that this IBI is a suitable tool for the assessment of the biological conditions of these streams. The highest IBI values were observed in the rainy season at the NF and SF sites, with significant differences between the NF and SC sites (Kruskal-Wallis test: P = 0.03). The results indicated some variability in the biological integrity at SF and SC sites, suggesting a relationship with the intensity of the management of this crop. Patterns were consistent with other studies that have shown the effects of agriculture on the environmental quality of streams, which indicate the importance of the riparian zone to the maintenance of ecosystem integrity and supports the use of the IBI for biological monitoring in similar regions.


Succination of proteins by fumarate: mechanism of inactivation of glyceraldehyde-3-phosphate dehydrogenase in diabetes.
S-(2-succinyl)cysteine (2SC) is a chemical modification of proteins formed by a Michael addition reaction between the Krebs cycle intermediate, fumarate, and thiol groups in protein--a process known as succination of protein. Succination causes irreversible inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in vitro. GAPDH was immunoprecipitated from muscle of diabetic rats, then analyzed by ultra-performance liquid chromatography-electrospray ionization-mass spectroscopy. Succination of GAPDH was increased in muscle of diabetic rats, and the extent of succination correlated strongly with the decrease in specific activity of the enzyme. We propose that 2SC is a biomarker of mitochondrial and oxidative stress in diabetes and that succination of GAPDH and other thiol proteins may provide the chemical link between glucotoxicity and the pathogenesis of diabetic complications.


Integrated Care for Older Adults Improves Perceived Quality of Care: Results of a Randomized Controlled Trial of Embrace.
All community-living older adults might benefit from integrated care, but evidence is lacking on the effectiveness of such services for perceived quality of care. To examine the impact of Embrace, a community-based integrated primary care service, on perceived quality of care. Stratified randomized controlled trial. Integrated care and support according to the "Embrace" model was provided by 15 general practitioners in the Netherlands. Based on self-reported levels of case complexity and frailty, a total of 1456 community-living older adults were stratified into non-disease-specific risk profiles ("Robust," "Frail," and "Complex care needs"), and randomized to Embrace or control groups. Embrace provides integrated, person-centered primary care and support to all older adults living in the community, with intensity of care dependent on risk profile. Primary outcome was quality of care as reported by older adults on the Patient Assessment of Integrated Elderly Care (PAIEC). Effects were assessed using mixed model techniques for the total sample and per risk profile. Professionals' perceived level of implementation of integrated care was evaluated within the Embrace condition using the Assessment of Integrated Elderly Care. Older adults in the Embrace group reported a higher level of perceived quality of care than those in the control group (B = 0.33, 95 % CI = 0.15-0.51, ES d = 0.19). The advantages of Embrace were most evident in the "Frail" and "Complex care needs" risk profiles. We found no significant advantages for the "Robust" risk profile. Participating professionals reported a significant increase in the perceived level of implementation of integrated care (ES r = 0.71). This study shows that providing a population-based integrated care service to community-living older adults improved the quality of care as perceived by older adults and participating professionals.


Impact of chitosan and polyacrylamide on formation of carbonaceous and nitrogenous disinfection by-products.
Coagulation is one of the most commonly used practices in water treatment to remove natural organic matter, which can serve as precursors for disinfection by-products (DBPs). Furthermore, some coagulant aids, particularly amine-based polymers, could foster the formation of both carbonaceous and nitrogenous DBPs (C-DBPs and N-DBPs, respectively). In this study, we evaluated the formation potentials of 11 C-DBPs and N-DBPs during chloramination when two coagulant aids, chitosan and polyacrylamide (PAM), were used under typical water treatment conditions. Our results suggest that both chitosan and PAM promote the formation of N-DBPs, while neither affects the formation of C-DBPs. We further investigated a potential method to mitigate the formation of N-DBPs. Methyl iodide (MeI), an alkylating agent, was effective at reducing the formation of N-DBPs by converting amine to quaternary ammonium groups in chitosan. 1H-NMR results confirmed that the quaternarization reaction did take place. This study reports that chitosan, a natural coagulant, and PAM contribute to the formation of toxic DBPs. More importantly, it provides a preventative strategy for curbing the formation of DBPs through chemical structural modification.


Identification of potential inhibitor targeting enoyl-acyl carrier protein reductase (InhA) in Mycobacterium tuberculosis: a computational approach.
The explosive global spreading of multidrug resistant Mycobacterium tuberculosis (Mtb) has provoked an urgent need to discover novel anti-TB agents. Enoyl-acyl carrier protein reductase from Mtb is a well-known and thoroughly studied target for anti-tuberculosis therapy. In the present analysis, virtual screening techniques performed from Drug bank database by utilizing INH-NAD adduct as query for the discovery of potent anti-TB agents. About 100 molecules sharing similar scaffold with INH-NAD adduct were analyzed for their binding effectiveness. The initial screening based on number of rotatable bonds gave 42 hit molecules. Subsequently, physiochemical properties such as toxicity, solubility, drug-likeness and drug score were analyzed for the filtered set of compounds. Final data reduction was performed by means of molecular docking and normal mode docking analysis. The result indicates that DB04362, adenosine diphosphate 5-(beta-ethyl)-4-methyl-thiazole-2-carboxylic acid could be a promising lead compound and be effective in treating sensitive as well as drug-resistant strains of Mtb. We believe that this novel scaffolds might be the good starting point for lead compounds and certainly aid the experimental designing of anti-tuberculosis drug in a short time.


The embryology of foregut malformations.
Developmental disorders in the period of the differentiation of the primitive foregut leads to atresia of the esophagus with tracheoesophageal fistula. Most authors think that this differentiation is caused by lateral foregut folds, which fuse in midline, thus forming the tracheoesophageal septum. In order to gain information about this period of development, we studied the foregut region of chick embryos by scanning electron microscopy (SEM) and light microscopy. In our study no signs of lateral folds or fusing foregut wall components, which were forming a tracheoesophageal septum, were found. Our study suggests that the development of the esophagus and trachea is the result of a simple reduction of the size of the primitive foregut. The consequence for the understanding of the embryology of the foregut malformations is discussed.


The immune restorative effect of Isoprinosine administration on the local graft-versus-host reaction of cancer patients.
The immunorestorative effect of Isoprinosine (ISO) in vivo on T-cell-induced local graft-versus-host reaction (GVHR) was analyzed in 60 cancer patients randomized into three groups: 20 patients received 1 g/day ISO orally for 7 days, 20 patients received 4 g/day ISO for 7 days, and 20 patients received no treatment for 7 days. The local GVHR was assessed before and after the 7 days of treatment (or no treatment). A significant augmentation of the local GVHR was observed among the ISO-treated patients (44.1 +/- 19.1 vs 61 +/- 37.1 for 1 g ISO, P less than 0.05; 42.1 +/- 20.1 vs 58.9 +/- 23.8 for 4 g of ISO, P less than 0.01). This was not so for patients who received no treatment (38.5 +/- 20.4 vs 38.3 +/- 21.2; P greater than 0.1). Nine patients treated with 1 g of ISO and 5 treated with 4 g of ISO/day, who were initially characterized by a negative local GVHR (less than 50 mm3), converted to a positive reaction (greater than or equal to 50 mm3) compared to none of the patients who received no treatment. Two patients treated with 1 g of ISO and 2 patients treated with 4 g, who initially had a positive GVHR, demonstrated further augmentation (greater than or equal to 50% increase) in the GVHR after 7 days of treatment. In 2 patients (one in each treated group) the ISO induced a suppression of the GVHR from positive to negative. Incubation of the patients' lymphocytes in vitro with ISO (100 micrograms/ml X 1 hr) failed to induce augmentation of the GVHR and did not correlate with the in vivo effect in the same patients. These results demonstrate an immunomodulatory effect of ISO in cancer patients and lend further support to the use of this drug as an immunomodulating therapy among cancer patients.


Influence of 13-cis and all-trans retinoic acid on rat embryonic development in vitro: correlation with isomerisation and drug transfer to the embryo.
In vitro experiments using whole rat embryo cultures show that all-trans retinoic acid (all-trans RA) administered at low concentrations (30 ng/ml culture medium) is 10 times more active than 13-cis retinoic acid (13-cis RA) and 3 times more active when administered at high concentrations (1000 ng/ml culture medium). Morphological investigation of the embryos shows that both substances directly influence embryonic development in an identical manner. Isomerisation products of the administered compounds (all-trans RA from 13-cis RA and vice versa) were detected by HPLC both in the culture medium and the embryo. Correlation of embryonic retinoid concentration with the observed effects led us to suggest that the isomerisation to all-trans RA is crucial in regard to 13-cis RA-induced abnormal embryonic development. A 100% effect can be induced in vitro with very low amounts of all-trans RA (7.2 ng/g) in the embryo.


Pentameric ellagitannin oligomers in melastomataceous plants--chemotaxonomic significance.
The pantropical plant family Melastomataceae produces characteristic hydrolyzable tannin oligomers. The latter in this family are distinguished from those in other plant families by the fact that the oligomers from dimers to tetramers are composed of two different alternating monomeric units: casuarictin and pterocaryanin C. These oligomers are metabolites that are produced by intermolecular C-O oxidative coupling between the monomers (or their desgalloyl-or des-hexahydroxydiphenoyl derivatives) forming a valoneoyl group as the link between monomers. The chemotaxonomically significant oligomerization pattern of melastomataceous plants provided helpful suggestions for determining the structures of new oligomers (nobotanins Q-T and melastoflorins A-D) isolated from Monochaetum multiflorum, which belongs to this family. Melastoflorins A-D were characterized as pentamers, which are the largest hydrolyzable tannins composed of different monomeric units.


New Approaches to Treating Challenging Subtypes of ALL in AYA Patients.
The treatment of acute lymphoblastic leukemia (ALL) in adolescent and young adult (AYA) patients has markedly improved with the adoption of pediatric-inspired protocols. However, there remain several subtypes of ALL that represent significant therapeutic challenges. Here, we review the current evidence guiding treatment of Philadelphia chromosome-positive (Ph+), Philadelphia chromosome-like (Ph-L), and early T-precursor (ETP) ALL in the AYA population. Clinical trials in Ph + ALL have demonstrated the superior efficacy of second- and third-generation tyrosine kinase inhibitors (TKIs) to induce and maintain remission. Current efforts now focus on determining the durability of these remissions and which patients will benefit from transplant. For Ph-like and ETP ALL, recent studies are investigating the addition of novel agents to standard treatment. The treatment of Ph + ALL has significantly improved with the addition of potent TKIs. However, the treatment of Ph-like and ETP ALL remains a challenge. At this time, the judicious use of allogenic transplant is the only current approach to modify this increased risk.


Multimodality, Multidirectional Resection of Craniopharyngioma: Versatility in Alternating the Principal and Auxiliary Surgical Corridors and Visualization Modalities.
Large tumors of the skull base may require multiple approaches for safe removal, as unidirectional approaches may require excessive brain retraction. Two patients underwent simultaneous, endoscopic and microscopic resection of tumors using 2 anatomic corridors. The corridor used for most of the tumor dissection was designated as "principal," whereas the secondary corridor used for assisting the main operation was designated "auxiliary." The endoscope and microscope were used interchangeably in the 2 corridors. For the first patient, the principal corridor was transventricular, and the auxiliary corridor was orbitofrontal. The endoscope was used exclusively in the latter and yielded visual information of the undersurface of the tumor, used for protection of the optic chiasm. For the second case, the corridors were reversed. Tumor resection was performed using the microscope and endoscope in alternating fashion. The endoscope, when used in the auxiliary ventricular corridor, was useful in delivering tumor components into the principal operative field. Multidirectional approaches to large tumors can be considered less invasive if the surgical corridors are combined in a way to minimize traction forces on both brain and tumor and maximize visualization and protection of critical structures. These combination approaches can be made simpler with the seamless integration of the endoscope and microscope. The choice between the principal and auxiliary corridors should alternate just as smoothly as the visual modality and must be dictated by the anatomy and minute-to-minute tactical situation during the operation.


Effects of two different types of ankle-foot orthoses on gait outcomes in patients with subacute stroke: a randomized crossover trial.
To identify whether patients in the subacute stage of stroke, with foot drop, would have better gait outcomes when using a double-adjustable AFO (DA AFO) or a posterior leaf spring AFO (PLS AFO) at baseline without practice and to determine whether one week of practice would significantly change gait outcomes with either of the AFOs. Within-subject 2 × 2 repeated measures design. Postacute and outpatient rehabilitation center. Twenty individuals with mean age of 57 years (SD: 12.0 years) with subacute stroke. Participants were measured using DA AFO and PLS AFO at baseline. Follow-up measurements were taken after one week of practice with each type of AFO in randomly assigned order. Gait endurance (6-Minute Walk Test (6MWT)), gait symmetry, and gait velocity at self-selected and fast-paced velocity measured using GAITRite gait analysis system and patient report of AFO preference. At baseline, no significant differences were found between the 2 AFOs (P > 0.05). There was no significant interaction (P > 0.05) of AFO and practice for gait endurance, symmetry, and velocity. Main effect of practice was significant for gait endurance (P < 0.001), self-selected velocity (P = 0.001), and fast-paced velocity (P < 0.001). In all, 16 participants preferred using DA AFO for walking. No difference between DA AFO and PLS AFO was found on measures of gait endurance, symmetry, and velocity at baseline or after practice. With practice over time, participants improved in gait endurance and velocity regardless of AFO type.


Effect of saliva on sperm motility and activity.
Infertile couples frequently experience sexual dysfunction during their infertility investigations, including inadequate vaginal lubrication. In a attempt to look for a lubricant that would not impair sperm motility and activity, saliva was added to normal semen from healthy male donors. Saliva induced a "shaking movement" in 12% of the total sperm population incubated with high concentrations of saliva. This phenomenon did not occur with low concentrations of saliva, but sperm motility and progression significantly decreased. The results indicate that saliva has a deleterious effect on sperm motility and activity and should not be encouraged as a vaginal lubricant for the infertile couple.


Evaluation of sepsis screen for diagnosis of neonatal septicemia.
Fifty clinically suspected cases of neonatal septicemia were studied for evaluating the role of sepsis screen. Sensitivity and specificity of C-reactive protein test, micro-ESR, gastric aspirate cytology for polymorphs and toxic granules in neutrophils were studied singly and in combinations of two and three tests. Positive blood culture was obtained in only 20% cases, thereby underlying the need for a sepsis screen in the diagnosis of neonatal septicemia, especially in areas where adequate micro-biological facilities are lacking.


Robotic versus laparoscopic left colectomy: a systematic review and meta-analysis.
This study aimed to review the new evidence to understand whether the robotic approach could find some clear indication also in left colectomy. A systematic review of studies published from 2004 to 2022 in the Web of Science, PubMed, and Scopus databases and comparing laparoscopic (LLC) and robotic left colectomy (RLC) was performed. All comparative studies evaluating robotic left colectomy (RLC) versus laparoscopic (LLC) left colectomy with at least 20 patients in the robotic arm were included. Abstract, editorials, and reviews were excluded. The Newcastle-Ottawa Scale for cohort studies was used to assess the methodological quality. The random-effect model was used to calculate pooled effect estimates. Among the 139 articles identified, 11 were eligible, with a total of 52,589 patients (RLC, n = 13,506 versus LLC, n = 39,083). The rate of conversion to open surgery was lower for robotic procedures (RR 0.5, 0.5-0.6; p < 0.001). Operative time was longer for the robotic procedures in the pooled analysis (WMD 39.1, 17.3-60.9, p = 0.002). Overall complications (RR 0.9, 0.8-0.9, p < 0.001), anastomotic leaks (RR 0.7, 0.7-0.8; p < 0.001), and superficial wound infection (RR 3.1, 2.8-3.4; p < 0.001) were less common after RLC. There were no significant differences in mortality (RR 1.1; 0.8-1.6, p = 0.124). There were no differences between RLC and LLC with regards to postoperative variables in the subgroup analysis on malignancies. Robotic left colectomy requires less conversion to open surgery than the standard laparoscopic approach. Postoperative morbidity rates seemed to be lower during RLC, but this was not confirmed in the procedures performed for malignancies.


Depression Symptom Severity and Cardiorespiratory Fitness in Healthy and Depressed Adults: A Systematic Review and Meta-Analysis.
Depression symptom severity and cardiorespiratory fitness (CRF) are significant predictors of mortality and disability. However, the relationship between the two is unclear. This meta-analysis assessed the relationship between depression symptom severity and CRF in healthy and depressed adults (aged 18 years and over). The PubMed, Cochrane Library, Google Scholar and ProQuest databases were browsed for relevant English-language studies published from January 2000 to August 2014. Studies reporting a correlation between a depression scale and maximum oxygen consumption (VO2peak), as well as studies from the data of which such a correlation could be calculated, were included in this analysis. Correlation coefficients (CCs) were converted to Fisher's z values, and the analysis was performed using a random-effects model. Then, summary effects and 95% confidence intervals (CIs) were converted back to CCs. Sixteen studies (totalling 4039 participants) were included in this analysis. A modest correlation between depression symptom severity and CRF was found (CC -0.16, 95% CI -0.21 to -0.10), appearing stronger in male participants (CC - 0.22, 95% CI -0.26 to -0.18) than in female participants (CC -0.12, 95% CI -0.19 to -0.05; p = 0.01). There was no difference in the summary effect between healthy and depressed adults (p = 0.43). Heterogeneity was moderate (I2 = 33%; p = 0.09). Depression symptom severity is inversely correlated with CRF, and this correlation is stronger in men than in women. Clinical and prognostic implications of the correlation are discussed. These findings should stimulate further research on the effects of treating one variable on the other.


Assaying sialyltransferase activity with surface plasmon resonance.
Here, we describe an activity assay for sialyltransferases based on surface plasmon resonance (SPR). Different natural and synthetic oligosaccharides serving as acceptor substrates for the sialyltransferase ST3Gal-III (EC 22.214.171.124) were immobilized or synthesized on SPR chips. The chip was then exposed to different concentrations of a reaction mixture of ST3Gal-III and CMP-Neu5Ac either by injection or by external application of the reaction mixture to the chip surface. The binding of two lectins, one that specifically recognizes the unmodified acceptor, the other the sialylated oligosaccharide, was utilized to determine the extent of enzymatic turnover. In order to obtain enzymatic activities, the SPR data were correlated to data obtained from a classical radio assay. After regeneration, that is, cleavage of the sialic acid residues by using a sialidase, the chip is available for new experiments. The technique allows the rapid determination of sialyltransferase activity with only nanomolar quantities of acceptor substrates and should be of particular value in cases in which a large variety of samples, including cell lysates, have to be screened for their enzymatic activities.


Arterial erectile dysfunction: reliability of new markers of endothelial dysfunction.
Blood endothelial progenitor cells (EPC) and microparticles (EMP) have been proposed as markers of endothelial dysfunction. Aim of this study was to evaluate a new immunophenotype of EPC and EMP in patients with arterial erectile dysfunction (AED) compared to psychogenic erectile dysfunction (PED). One hundred patients (63.2±2.6 yr) with AED were enrolled in this study. Their EPC and EMP concentrations were compared to those of 40 patients with PED (64.2±2.7 yr). EPC (CD45(neg)/CD34(pos)/ CD144(pos)) and EMP (CD45(neg)/CD144(pos)/AnnexinV(pos)) blood concentrations were evaluated by flow cytometry. Patients with AED had significantly higher blood pressure, triglycerides, homeostasis model assessment index of insulin resistance, and cavernous artery acceleration time and intima-media thickness than PED; whereas international index of erectile function 5 score, HDL-cholesterol, and cavernous artery peak systolic velocity was lower than PED. Both EPC and EMP were significantly higher in patients with AED compared to patients with PED. Patients with AED showed worse metabolic parameters, cavernous artery parameters, and higher EPC and EMP compared to patients with PED. This suggests that AED is an expression of endothelial dysfunction and that EPC and EMP may be considered predictors of endothelial dysfunction in patients with AED.


Levels of intracellular HIV-DNA in patients with suppressive antiretroviral therapy.
The objective of this study is to study factors associated with HIV-DNA levels in chronically infected patients on long-term suppressive antiretroviral therapy (ART). A cross-sectional, multicentre study of patients receiving ART for more than 3 years, HIV-RNA less than 50 copies/ml for more than 2 years and CD4 cell count more than 350 cells/μl. Factors associated with low (<150) or high (>1000), compared with intermediate (150-1000 copies/10 PBMCs) levels of HIV-DNA were investigated using multinomial logistic regression. Five hundred and twenty-two patients who initiated ART during the chronic phase were included (71% male; median peak HIV-RNA: 4.88 log10 copies/ml, CD4 cell count nadir: 222 cells/μl). Median ART duration was 13 years [interquartile range (IQR) 7-17], viral suppression was 5.7 years (IQR 3.9-8.5) and 66% of the patients never experienced ART failure. Median HIV-DNA was 323 copies/10 PBMCs (IQR, 129-717) with low, intermediate and high levels observed in 28.3, 55.4 and 16.3%, respectively. In multivariable analysis, women were more likely to achieve a low level of HIV-DNA. Each additional year with suppressed HIV-RNA increased the likelihood of low level and decreased the likelihood of high level of HIV-DNA. Peak HIV-RNA higher than 5log10 was always associated with a decreased risk of low and an increased risk of high HIV-DNA. For patients with peak HIV-RNA lower than 5log10, past ART failure was associated with high level of HIV-DNA. Chronically HIV-infected patients with long-term suppressive ART can achieve low total HIV-DNA but one over six still presented HIV-DNA above 1000 copies/10 PBMCs despite long-term viral suppression.


Modulation of L-type calcium current in rat cardiac myocytes by sulfur dioxide derivatives.
The effects of sulfur dioxide (SO(2)) derivatives (bisulfite and sulfite, 1:3M/M) on voltage-dependent L-type calcium current (I(Ca,L)) in isolated rat ventricular myocytes were studied using the whole cell patch-clamp technique. SO(2) derivatives increased I(Ca,L) in a concentration-dependent manner. SO(2) derivatives shifted both the steady-state activation and the inactivation curves of I(Ca,L) to more positive potentials, the effect on the latter being more pronounced. SO(2) derivatives markedly accelerated the recovery of I(Ca,L) from inactivation. SO(2) derivatives also significantly shortened the fast and slow time constants of inactivation. These results suggested that SO(2) inhalation might cause cardiac myocyte injury through increasing intracellular calcium via voltage-gated calcium channels.


Nuclear transformation of Chlamydomonas reinhardtii: A review.
Chlamydomonas reinhardtii is a model organism with three sequenced genomes capable of genetic transformation. C. reinhardtii has the advantages of being low cost, non-toxic, and having a post-translational modification system that ensures the recombinant proteins have the same activity as natural proteins, thus making it a great platform for application in molecular biology and other fields. In this review, we summarize the existing methods for nuclear transformation of C. reinhardtii, genes for selection, examples of foreign protein expression, and factors affecting transformation efficiency, to provide insights into effective strategies for the nuclear transformation of C. reinhardtii.


Immunotherapy for hepatoma using a dual-function vector with both immunostimulatory and pim-3-silencing effects.
Tumorigenesis is an immortalization process in which the growth of normal cells is uncontrolled and programmed cell death is suppressed. Molecular biologic and immunologic studies have revealed that the aberrant expression of some proto-oncogenes boosts proliferation and inhibits apoptosis, which is vital for tumor development. The hypofunction of the host immune system also drives the development and metastasis of malignant tumors. Pim-3, a member of the Pim family, is aberrantly expressed in several cancers. Data suggest that Pim-3 inhibits apoptosis by phosphorylating the proapoptotic BH3-only protein Bad. Here, we constructed a dual-function small hairpin RNA (shRNA) vector containing an shRNA targeting Pim-3 and a TLR7-stimulating ssRNA. Stimulation with this bi-functional vector in vitro promoted significant apoptosis of Hepa1-6 cells by regulating the expression of apoptosis-related proteins and induced secretion of type I IFNs. Most importantly, this bi-functional vector more effectively inhibited subcutaneous Hepa1-6 cell growth than did single shRNA and ssRNA treatment in vivo. Natural killer (NK), CD4(+) T, and CD8(+) T cells and macrophages were required for effective tumor suppression, and CD4(+) T cells were shown to play a helper role in the activation of NK cells, possibly by regulating the secretion of Th1 or Th2 cytokines. This ssRNA-shRNA bi-functional vector may represent a promising approach for tumor therapy.


Pathological features of Cryptosporidium andersoni-induced lesions in SCID mice.
To assess the infectivity and the istopathological features of Cryptosporidium andersoni (C. andersoni) in laboratory animals, SCID mice were orally inoculated with oocysts of C. andersoni. Starting one week after inoculation, the SCID mice began shedding oocysts, and this continued for ten weeks. Histopathologically, myriads of C. andersoni were observed on the apical surface of the epithelium in the gastric pit of the glandular stomach. There were few lesions in the gastric epithelium except C. andersoni adhesion. In the lamina propria of the affected mucosa, minimum infiltration of inflammatory cells was observed. Immunohistochemically, C. andersoni demonstrated a positive reaction to a number of primary antibodies of Cryptosporidium parvum. In the experiment described here, few increases were seen in apoptotic epithelial cells in the affected mucosas of the SCID mice, and the nuclear augmentation was not enhanced. It was hypothesized that the absence of apoptosis and cell division were due to a lack of inflammatory cell reaction in the lamina propria.


"The trauma machine expands faster than our services": Health risks for unhoused people in an early-stage gentrifying area.
While homelessness continues to be a prevalent problem throughout the United States, many urban neighborhoods are also concurrently experiencing an influx of affluent neighbors through gentrification, exposing the stark inequalities in housing access nationwide. Gentrification-induced changes in neighborhood dynamics have also been shown to affect the health of low-income and non-white groups, with high risks of trauma from displacement and exposure to violent crime and criminalization. This study addresses risk factors for health among the most vulnerable, unhoused individuals, and provides a detailed case study on the potential exposures to emotional and physical traumas for unhoused people in early-stage gentrifying areas. By conducting 17 semi-structured interviews with people who work with the unhoused community - health providers, nonprofit employees, neighborhood representatives, and developers - in Kensington, Philadelphia, we analyze how early-stage gentrification impacts the risks for negative health consequences among unhoused groups. Results show that gentrification impacts the health of unhoused people in four main areas that, all together, create what we identify as a "trauma machine" - that is compounding traumas for unhoused residents by 1) reducing and compromising spaces of safety from violent crime, 2) decreasing public services, 3) threatening the quality of healthcare, and 4) increasing the likelihood of displacement and associated trauma.


Baseline Body Surface Area and Itch Severity Define Response to Baricitinib in Patients with Moderate-to-Severe Atopic Dermatitis at Week 16.
Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by heterogeneous clinical phenotypes and high symptom burden, especially through itch. Baricitinib (BARI), an oral Janus Kinase 1/2 inhibitor, is approved in Europe, Japan, and other countries, for treatment of adults with moderate-to-severe AD who are candidates for systemic therapy. This post hoc analysis of a Phase 3 topical corticosteroid (TCS) combination therapy trial (BREEZE-AD7) aims to characterize patients who might benefit most from BARI. Classification and regression tree (CART) analysis was used to identify baseline predictors for patients treated with BARI 4-mg, who achieved ≥ 75% improvement in Eczema Area and Severity Index (EASI75), or EASI75 or Itch Numerical Rating Scale (NRS) ≥ 4-point improvement at week 16 (responders), versus non-responders. Subgroup efficacy analyses were performed based on identified predictor variables, combined with Itch NRS < 7/ ≥ 7. Missing data were imputed as non-responder. Baseline body surface area (BSA) was identified by CART as strongest variable predicting response to BARI at week 16, with a cut-off around 40% (BSA ≤ 40%). When combining BSA with itch severity, highest response rates were achieved by BARI patients with BSA ≤ 40%/Itch NRS ≥ 7 at baseline. In this subgroup, 69% and 58% of patients treated with BARI 4-mg achieved EASI75 and Itch NRS ≥ 4-point response at week 16, respectively. While these response rates were 65% and 50% for BARI 4-mg patients with baseline BSA ≤ 40%/Itch NRS < 7, they were 33% and 11% in BSA > 40%/Itch NRS < 7, and 32% and 49% in BSA > 40%/Itch NRS ≥ 7 subgroups, respectively. Using a machine learning approach, patients with moderate-to-severe AD and a BSA affecting 10-40% and Itch NRS ≥ 7 were characterized as likely to benefit most from BARI 4-mg TCS combination therapy. This was confirmed by subgroup analyses, which showed that these patients are most likely to show favorable response rates in improving AD signs and symptoms, specifically itch, after 16 weeks of treatment.


Bi-spectral index, entropy and predicted plasma propofol concentrations with target controlled infusions in Indian patients.
Many processed electroencephalographic signals are used now to help the anaesthesiologist titrate the depth of sedation. We investigated the relationship between target plasma propofol concentration and objective end-points of sedation- Bispectral Index (BIS), State Entropy (SE) and Response Entropy (RE)-at clinical end-points as assessed by Modified Observer Assessment of Alertness/sedation Scale (MOAAS) in Indian patients. Eighteen ASA 1 and 2 Indian adult patients scheduled to undergo elective surgery were included. The target control infusion (TCI) of propofol was administered using 'Diprifusor'. The level of sedation was assessed using MOAAS by the anaesthesiologist. BIS, SE, RE were recorded throughout. TCI was started at 0.5 μg/ml and increased by 0.5 μg/ml every 6 min till MOAAS scores reached 0 or there was sustained BIS value less than 30. The EC(50) and EC(95) of predicted plasma propofol concentration for loss of consciousness (assessed by loss of response to verbal command), were 2.3 and 2.8 μg/ml respectively and for loss of response to painful stimuli (trapezius squeeze) were 4.0 and 5.0 μg/ml respectively. The BIS and entropy values (EC(50) and EC(95)) for loss of consciousness and response to painful stimuli in Indian patients were estimated. The preliminary relation of target plasma propofol concentration with BIS was found to be BIS = 100.5-16.4 × (Target concentration). The target plasma propofol concentrations required to produce unconsciousness and loss of response to painful stimuli in Indian patients have been estimated. Also, the relations between target plasma concentration and objective measures of different levels of anaesthesia have been established.


Suicidal ideation and intentional self-harm in pregnancy as a neglected agenda in maternal health; an experience from rural Sri Lanka.
Suicide only present the tip of the iceberg of maternal mental health issues. Only a fraction of pregnant women with suicidal ideation proceeds to intentional self-harm (ISH) and even a smaller proportion are fatal. The purpose of the present study was to determine the prevalence of depression, suicidal ideation (present and past) and history of ISH among pregnant mothers in rural Sri Lanka. We have conducted a hospital based cross sectional study in the third largest hospital in Sri Lanka and an another tertiary care center. Pregnant women admitted to hospital at term were included as study participants. The Edinburgh Postpartum Depression Scale (EPDS), a self-administered questionnaire for demographic and clinical data and a data extraction sheet to get pregnancy related data from the pregnancy record was used. The study sample consisted of 475 pregnant women in their third trimester. For the tenth question of EPDS "the thought of harming myself has occurred to me during last seven days" was answered as "yes quite a lot" by four (0.8%), "yes sometimes" by eleven (2.3%) and hardly ever by 13 (2.7%). Two additional pregnant women reported that they had suicidal ideation during the early part of the current pregnancy period though they are not having it now. Four (0.8%) pregnant women reported having a history of ISH during the current pregnancy. History of ISH prior to this pregnancy was reported by eight women and five of them were reported to hospitals, while others were managed at home. Of the 475 pregnant females included in the study, 126 (26.5%) had an EPDS score more than nine, showing probable anxiety and depression. Pregnant women who had primary/post-primary or tertiary education compared to those who were in-between those two categories were at higher risk of high EPDS score with a OR of 1.94 (95% CI 1.1-3.3). Reported suicidal ideation prior to pregnancy was also associated with high EPDS with a OR of 6.4 (95% CI 2.3-17.5). Based on our data, we conservatively estimate around 500 pregnant women each year having suicidal ideation and, 130 ISH annually in Anuradhapura, which should be considered as a high priority for an urgent intervention.


Playground activities and gender variation in objectively measured physical activity intensity in Australian primary school children: a repeated measures study.
Recent studies have sought to address the limited time for physical activity by focusing on increasing physical activity intensity among students during non-curricula periods and specifically school break times. We objectively measured the intensity of student physical activity (PA) during recess and lunch breaks at primary schools in the Western Sydney region of New South Wales (NSW), Australia using a 12-month repeated measures observation design study. Systematic direct observation of recess and lunch breaks over a ten-week period in 2014 and 2015. 120 recess and lunch breaks across twenty schools (2014) with 839 periodic observations and across 15 schools with 587 periodic observations in 2015. Both observation periods were conducted over 10-weeks in Term 4 (September - December). The mean proportion of vigorous physical activity reported as a percentage (%VPA) across both time points was 16.6% (SD = 23.4). 36.8% (SD = 26.0) of time was spent walking and the remaining time (46.6%; SD = 30.4) was spent in sedentary activities. There was a significant decline in %VPA and increase in sedentary activity (p < 0.01) between the two time periods of measurement. In 2014, boys spent twice as much time in %VPA than girls during breaks in the school day and in 2015 this increased to nearly three times as much time in %VPA. %VPA also varied on the type of surface PA took place and the types of activities the children were allowed to undertake during breaks. Recess and lunch breaks potentially offer an opportunity for children to participate in unstructured PA during the school day. Substantial variations in the %VPA during these periods exist. Addressing playground gender participation disparities and space usability/accessibility may be a necessary first step in promoting higher PA intensities during breaks.


Glutamine synthetase in cultured whole retinas from the embryonic chick. Role of protein and RNA syntheses in 4 degrees C storage enhancement.
Glutamine synthetase (GS) activity is enhanced in cultured whole retinas when a 72 h incubation at 37 degrees C is preceded by storage at 4 degrees C for 2-24 h. This enhancement occurs even in the absence of glucocorticoids and is maximal in retinas from 11 to 14 d embryos. In comparison, cortisol-induced increases in retinal GS activity at 37 degrees C are optimal in retinas from 8 to 12 d embryos. This study, using cycloheximide (an inhibitor of protein synthesis) and cordycepin (an inhibitor of RNA synthesis), indicates that both protein and RNA synthesis are required for the 4 degrees C storage enhancement of GS activity. The necessary RNA synthesis occurs within the first 48 h following transfer to 37 degrees C and does not require concomitant protein synthesis. Uridine uptake, but not incorporation into trichloroacetic acid-precipitable material, is increased by initial 4 degrees C storage when compared with whole retina controls incubated at 37 degrees C for the total time. In contrast, both uptake and incorporation of amino acids are increased in 4 degrees C-stored retinas for as long as 72 h subsequent to transfer from 4 to 37 degrees C. This suggests that enhancement GS activity may arise from a combination of elevated general protein synthesis and specific messenger-RNA synthesis following 4 degrees C storage.


Limitations of routine neuroimaging in predicting outcomes of preterm infants.
Preterm births are increasing in number and while the rates of cerebral palsy have declined, there are increasing numbers of infants who survive with handicaps. In some studies, up to 50 % of children will have morbidity when followed up to school age. A review of current literature was conducted to determine the validity of routine cranial ultrasound scans (CUS) to predict neurodevelopmental outcomes, including motor and cognitive deficits. We also reviewed the additional benefit offered by including MRI scans in scanning protocols to enhance the reliability in predicting the neurodevelopmental sequelae of prematurity. CUS is valuable as a screening tool to determine significant brain injury when conducted regularly over the first weeks of life in preterm infants. Subtle changes on CUS are difficult to interpret and more precise information is offered by performing MRI scans. These are most often carried out at term equivalent age but earlier scans may be just as useful in predicting neurocognitive outcomes. When MRI scans are either normal or seriously abnormal, there is a very clear correlation with outcome to 2 years of age. Mild and moderate degrees of injury defined on MRI need more sophisticated scanning sequences to determine the likelihood of associated sequelae. Follow-up to school age is essential to diagnose more subtle cognitive delays. CUS provides a good screening tool to detect serious brain injury resulting in motor handicaps but MRI scans are complementary and necessary to accurately predict the outcomes of preterm infants, especially cognitive delays.


PERK in beta cell biology and insulin biogenesis.
PERK (EIF2AK3) was originally discovered as a major component of the unfolded protein response (UPR). PERK deficiency results in permanent neonatal diabetes, which was initially thought to be caused by a failure to regulate ER stress in insulin-secreting beta cells, culminating in beta cell death. However, subsequent studies found that low beta cell mass was a result of reduced cell proliferation, rather than increased apoptosis. Genetic and cellular studies of Perk-deficient beta cells showed that PERK was crucially required for ER functions including proinsulin trafficking and quality control, unrelated to the ER stress pathway. Under normal physiological conditions, changes in ER calcium levels, mediated by glucose and other insulin secretagogues, regulate PERK activity for the purpose of controlling insulin biogenesis.


What factors are predictors of emotional health in patients with full-thickness rotator cuff tears?
The importance of emotional and psychological factors in treatment of patients with rotator cuff disease has been recently emphasized. Our goal was to establish factors most predictive of poor emotional health in patients with full-thickness rotator cuff tears (FTRCTs). In 2007, we began to prospectively collect data on patients with symptomatic, atraumatic FTRCTs. All patients completed a questionnaire collecting data on demographics, symptom characteristics, comorbidities, willingness to undergo surgery, and patient-related outcomes (12-Item Short Form Health Survey, American Shoulder and Elbow Surgeons score, Western Ontario Rotator Cuff Index [WORC], Single Assessment Numeric Evaluation score, Shoulder Activity Scale). Physicians recorded physical examination and imaging data. To evaluate the predictors of lower WORC emotion scores, a linear multiple regression model was fit. Baseline data for 452 patients were used for analysis. In patients with symptomatic FTRCTs, the factors most predictive of worse WORC emotion scores were higher levels of pain (interquartile range odds ratio, -18.9; 95% confidence interval, -20.2 to -11.6; P < .0001) and lower Single Assessment Numeric Evaluation scores (rating of percentage normal that patients perceive their shoulder to be; interquartile range odds ratio, 6.2; 95% confidence interval, 2.5-9.95; P = .0012). Higher education (P = .006) and unemployment status (P = .0025) were associated with higher WORC emotion scores. Education level, employment status, pain levels, and patient perception of percentage of shoulder normalcy were most predictive of emotional health in patients with FTRCTs. Structural data, such astendon tear size, were not. Those with poor emotional health may perceive their shoulder to be worse than others and experience more pain. This may allow us to better optimize patient outcomes with nonoperative and operative treatment of rotator cuff tears.


Seasonal prevalence of anti-Japanese encephalitis virus antibody in pigs in different regions of Taiwan.
Although the endemic season of Japanese encephalitis lasts from May through October, sporadic cases occur in other months of the year. To appreciate the real situation of Japanese encephalitis virus (JEV) activity throughout the year, a survey was conducted using hemagglutination-inhibition test to detect the presence of anti-JEV antibodies in pigs' sera, which were collected from 4 regions of Taiwan between January 2000 and January 2001. Results indicate that (1) JEV-infected pigs were found throughout the year; (2) the prevalence rates of JEV in the 4 regions in descending order were 70% in Miaoli, 59% in Hualien, 52% in Pingtung, and 49% in Nantou; (3) similar to that in 1990, the peak endemic months appeared 1 month after the date of 50% seroconversion (May 21, 2000); (4) infected pigs were present during the period from December through April as a reservoir for over-wintering of JEV; and (5) there was a suggestive evidence for the occurrence of sporadic cases of JEV during the December-April period. In conclusion, JEV propagates and is active indigenously in the winter as well as other seasons of the year.


The effects of chrysomelid beetle grazing and plant competition on the growth of Rumex obtusifolius.
The interaction between grazing by Gastrophysa viridula and interspecific plant competition was investigated for Rumex obtusifolius growing in the field. During an eight-month growing season non-competing R. obtusifolius grew larger than competing plants although herbivore loads (beetle productivity per unit leaf area) were similar for competing and non-competing plants. However, grazing significantly reduced the growth of R. obtusifolius only in competing plants thus demonstrating a synergism between plant competition and invertebrate herbivory. The relevance of these findings for the distribution of plant species is discussed.


Effect of passive tilt on sympathetic and parasympathetic components of heart rate variability in normal subjects.
Decreased heart rate (HR) variability has been shown to be an independent predictor of poor outcome after acute myocardial infarction. Presumably, both reduced parasympathetic activity and increased sympathetic activity contribute to this observed HR variability response. To elucidate the physiologic contributions of the sympathetic and parasympathetic nervous systems to HR variability, the effect of passive head-up tilt (+70 degrees) was investigated on 4 indexes of HR variability in 17 healthy subjects. The standard deviation of the mean of 512 consecutive RR intervals, a traditional marker of HR variability and a purported index of cardiac parasympathetic neural tone, was compared with the mean difference of 512 consecutive RR intervals, with the maximal expiratory RR interval to minimal inspiratory RR interval ratio (respiratory RR ratio) and with the low- and high-frequency components of the power spectrum of 512 consecutive RR intervals. Passive tilt produced a nonsignificant decrease in the standard deviation of RR intervals. There was, however, a highly significant decrease in the mean difference of consecutive RR intervals and the high-frequency component of the RR-interval spectrum. Both the respiratory RR ratio and the low-frequency component of the RR-interval spectrum increased with tilt. It was concluded that the mean difference of consecutive RR intervals and the high-frequency component of the RR-interval spectrum are potentially superior indexes of "pure" parasympathetic neural tone and may be preferable for future use in cardiovascular studies of autonomic dysfunction.


Inflammatory breast cancer.
Of all malignancies in women, perhaps none is as lethal or as frustrating to the surgeon as inflammatory breast cancer. No significant progress in curing or controlling inflammatory breast cancer was made until the last decade, when investigators, noting the futility of local therapies, applied systemic therapies with some significant improvement in survival. This article outlines the epidemiology, clinical signs, differential diagnosis, pathology, and treatment of this disease.


Clinical and histopathologic examination of renal allografts treated with tacrolimus (FK506) for at least one year.
We clinically and pathologically analyzed renal allografts from 1 9 renal transplant patients treated with tacrolimus (FK506) for more than 1 year. Twenty-six renal allograft biopsy specimens from 1 9 renal transplant patients who underwent transplantations between 1991 and 1993 were evaluated. Thirteen biopsies were performed from stable functioning renal allografts with informed consent (nonepisode biopsy) and the other 13 were from dysfunctional renal allografts with a clinical indication for biopsy (episode biopsy). The main pathologic diagnoses (some overlap) were acute rejection (AR; n = 4), chronic rejection (CR; n=5), AR+CR (n =4), recurrent IgA nephropathy (n =5), normal findings (n =2), minimal-type chronic FK506 nephropathy (n = 9), and mild-type FK506 nephropathy (n = 11). Of the nonepisode biopsies, 7 and 4 biopsies showed minimal-type and mild-type chronic FK506 nephropathy, respectively. Chronic FK506 nephropathy consisted of rough and foamy tubular vacuolization (5 biopsies), arteriolopathy (angiodegeneration of the arteriolar wall; 20 biopsies), focal segmental glomerulosclerosis (4 biopsies) and the striped form of interstitial fibrosis (11 biopsies). The serum creatinine levels of patients in the mild-type chronic FK506 nephropathy group, which included 7 episode biopsies, were statistically higher than those in the minimum-type chronic FK506-nephropathy group (P< 0.001). This study demonstrates that chronic FK506 nephropathy consists primarily of arteriolopathy manifesting as insudative hyalinosis of the arteriolar wall, and suggests that mild-type chronic FK506 nephropathy is a condition which may lead to deterioration of renal allograft function.


Nonarthroplasty Options for the Athlete or Active Individual with Shoulder Osteoarthritis.
The management of glenohumeral osteoarthritis is difficult in young, active individuals. After nonoperative management fails, arthroscopic debridement with concomitant procedures (eg, loose body removal, capsular release, labral debridement, synovectomy, osteophyte resection, bursectomy, subacromial decompression, microfracture, and biceps tenotomy or tenodesis) to address potential pain generators may be an option in small, contained, unipolar lesions.


Reversibility of changes in evoked spinal response following graded spinal cord compression.
The spinal evoked response obtained in cats at a site immediately rostral to the site of a graded spinal cord compression is described. They usually show an earlier decrease in amplitude than cortical SEP's and the appearance of a particular positive potential. The degree of reversibility after decompression is variable and is not correlated with histological damage.


Does Kinesio taping in addition to exercise therapy improve the outcomes in subacromial impingement syndrome? A randomized, double-blind, controlled clinical trial.
The aim of this study was to determine the effectiveness of Kinesio taping (KT) application added to the exercise treatment of subacromial impingement syndrome (SIS). Thirty-eight (25 female, 13 male) patients with SIS were randomly divided into therapeutic KT (n=19) and sham KT (n=19) groups. All patients received the same exercise therapy in addition to therapeutic or sham KT at 3-day intervals for 12 days. The groups were compared according to pain, range of motion (ROM), muscle strength and DASH and Constant scores before treatment and at the 5th and 12th treatment days. Within group comparisons showed significant improvements in both groups at the 5th and 12th day evaluations (p<0.05). In comparisons between the groups, pain with movement and DASH scores in the therapeutic group were significantly lower at the 5th day (p<0.01). There were significant improvements in night pain, pain with movement, DASH score, shoulder external rotation muscle strength, and pain free shoulder abduction ROM in the therapeutic group at the 12th day (p<0.05). Passive shoulder flexion ROM increased more in the sham group at the 12th day (p<0.05). The addition of KT application to the exercise program appears to be more effective than the exercise program alone for the treatment of SIS.


Tumors of the Neurohypophysis: One Unit's Experience and Literature Review.
To evaluate and understand the clinical behavior and radiologic correlates of tumors originating from the posterior pituitary gland. To review the management strategy for these rare tumors and add to the limited existing literature. Retrospective review of 8 cases (5 pituicytomas, 2 spindle cell oncocytomas, and 1 granular cell tumor) managed at our institution between 2004 and 2019. The patients' clinical course, histologic features, and radiologic findings were reviewed. Their management and long-term follow-up is presented and compared with the literature. Long-term follow-up ranged from 1 to 9 years. There was 1 recurrence in a patient with spindle cell oncocytoma, and this was treated with radiotherapy. The endoscopically managed cases resulted in complete tumor excision with no recurrence. Epidemiologic data on primary tumors of the neurohypophysis is limited because of the rarity of these tumors. This study adds to the literature that these tumors behave as World Health Organization grade I tumors, although close follow-up is recommended as a few cases have shown recurrence. The endoscopic approach resulted in better gross total tumor resection rate in this series.


Hepatitis E virus in donor plasma collected in Japan.
Human hepatitis E virus (HEV) is prevalent worldwide. Iatrogenic HEV has recently been identified based on the reports of transfusion-transmitted cases. The detection rate of HEV-RNA and seroprevalence of HEV-IgG/IgM have been regionally evaluated in Japan, and donor plasma collected in Hokkaido is currently screened by nucleic acid amplification testing. However, the detection rate of HEV-RNA in blood donors in Japan outside of Hokkaido has not been reported. A total of 620 140 qualified donor plasma samples from Japanese regions excluding Hokkaido were tested for HEV-RNA (pools of 50 or 500) between 2004 and 2014. HEV-RNA-positive plasma bags were identified, and the HEV viral load, genotype and anti-HEV immunoglobulin (Ig)G/IgM were evaluated. The detection rate of HEV-RNA (pools of 50) was 1/15 075 and higher in eastern than in western Japan. All 36 HEV-RNA-positive samples were genotype 3 with viral load ranging from <1·69 to 7·22 log10 copies/ml. Our detection rate of HEV-RNA in donor populations in Japan outside Hokkaido (1/15 075 donations) is generally lower than reported in Europe and lower than previously reported for Hokkaido (1/8173 donations). As methods varied, we cannot exclude that these differences are reflective of differing RNA detection limits. In contrast to Hokkaido where genotype 4 has been reported among blood donations, all our positive donations were genotype 3, which is less pathogenic.


Contemporary developments in the utilization of metal-ceramic restorations: a review.
Numerous porcelain systems and techniques are currently available for utilization in full-coverage anterior crown restorations. Significant improvements have been made in the placement of margins and the reduction of the metal framework in order to enhance the optical effects (e.g., illumination, warmth, and vitality) of these porcelain systems. This article presents several recent developments in the fabrication of metal-ceramic crown restorations, and demonstrates the use of these principles in the aesthetic oral rehabilitation.


Insights into the degradation process of phenol during in-situ thermal desorption: The overlooked oxidation of hydroxyl radicals from oxygenation of reduced Fe-bearing clay minerals.
In-situ thermal desorption (ISTD) has attracted increasing attention owing to the efficient removal of organic contaminants from contaminated sites. However, it is poorly understood that whether and to what extent contamination degradation occurs upon oxygenation of reduced Fe-bearing clay minerals (RFC) in the subsurface during ISTD. In this study, we evaluated the mechanism of contaminant degradation upon oxygenation of reduced clay minerals during the ISTD. Reduced nontronite (rNAu-2) and montmorillonite (rSWy-3) were selected as RFC models. Results showed that thermal treatment during ISTD could significantly enhance phenol degradation, which increased from 25.8 % at 10 °C to 74.4 % at 70 °C in rNAu-2 and from 17.7 % at 10 °C to 49.8 % at 70 °C in rSWy-3. Correspondingly, the cumulative •OH at steady-state ([•OH]ss) increased by 3.7 and 1.5 times, respectively. The acceleration of Fe(II) oxidation with increasing temperature could be mainly responsible for [•OH]ss generation, which degrades phenol. Moreover, thermal treatment improved the fast oxidation of trioctahedral entities Fe(II)Fe(II)Fe(II) (TOF) and the slow oxidation of dioctahedral entities Fe(II)Fe(II) (DTF1), AlFe(II) (DAF1), and Fe(II)Fe(III) (DTF2). Our study suggests that the overlooked degradation progress of phenol by oxygenation of RFC during ISTD, and it could be favorable for contaminant degradation during remediation.


Calcitonin depresses amphetamine-induced locomotor activity.
Synthetic salmon calcitonin (sCT), given subcutaneously (6.4 micrograms/kg) or intracerebroventricularly (ICV, 30-600 ng), depressed amphetamine-induced locomotor activity in rats by more than 50%. ICV injection of sCT, either three hours or immediately before intraperitoneal amphetamine (1-3 mg/kg), significantly reduced the amphetamine-induced activity. In the absence of amphetamine, sCT had no effect on locomotor activity during the first 100 minutes after treatment. These results show sCT can act centrally to modify drug-induced behavior and may be related to reports of calcitonin receptors and calcitonin-like peptides in the brain.