ATP sensing in living plant cells reveals tissue gradients and stress dynamics of energy physiology.
Growth and development of plants is ultimately driven by light energy captured through photosynthesis. ATP acts as universal cellular energy cofactor fuelling all life processes, including gene expression, metabolism, and transport. Despite a mechanistic understanding of ATP biochemistry, ATP dynamics in the living plant have been largely elusive. Here, we establish MgATP2- measurement in living plants using the fluorescent protein biosensor ATeam1.03-nD/nA. We generate Arabidopsis sensor lines and investigate the sensor in vitro under conditions appropriate for the plant cytosol. We establish an assay for ATP fluxes in isolated mitochondria, and demonstrate that the sensor responds rapidly and reliably to MgATP2- changes in planta. A MgATP2- map of the Arabidopsis seedling highlights different MgATP2- concentrations between tissues and within individual cell types, such as root hairs. Progression of hypoxia reveals substantial plasticity of ATP homeostasis in seedlings, demonstrating that ATP dynamics can be monitored in the living plant.


Single-session manualized ego state therapy (EST) for combat stress injury, PTSD, and ASD, Part 2: the procedure.
An abbreviated description of our single-session 5- to 6-hour procedure is provided. In contrast to trauma reframing approaches, such as cognitive processing therapy (CPT) or traditional psychoanalytic interventions, our manualized procedure rapidly demystifies subconscious processes, making them accessible and understandable by the patient. The therapist's supportive ego strength is integrated into the intense repeated emotional and physiological releases of the traumatized ego states. The abreactive component of this 5-phase procedure exhausts the bound-up psychological and physiological reactions but also serves to quickly overcome the trauma and to restructure the personality. The patient becomes empowered to release the trauma memories and to emerge with the ability to be adaptive, assertive, giving, strong, and able to express anger appropriately yet be caring with family/friends.


Restoration of peroxisomal catalase import in a model of human cellular aging.
Peroxisomes play an important role in human cellular metabolism by housing enzymes involved in a number of essential biochemical pathways. Many of these enzymes are oxidases that transfer hydrogen atoms to molecular oxygen forming hydrogen peroxide. The organelle also contains catalase, which readily decomposes the hydrogen peroxide, a potentially damaging oxidant. Previous work has demonstrated that aging compromises peroxisomal protein import with catalase being particularly affected. The resultant imbalance in the relative ratio of oxidases to catalase was seen as a potential contributor to cellular oxidative stress and aging. Here we report that altering the peroxisomal targeting signal of catalase to the more effective serine-lysine-leucine (SKL) sequence results in a catalase molecule that more strongly interacts with its receptor and is more efficiently imported in both in vitro and in vivo assays. Furthermore, catalase-SKL monomers expressed in cells interact with endogenous catalase subunits resulting in altered trafficking of the latter molecules. A dramatic reduction in cellular hydrogen peroxide levels accompanies this increased peroxisomal import of catalase. Finally, we show that catalase-SKL stably expressed in cells by retroviral-mediated transduction repolarizes mitochondria and reduces the number of senescent cells in a population. These results demonstrate the utility of a catalase-SKL therapy for the restoration of a normal oxidative state in aging cells.


Telephone health care: it's more than just a phone call.
Telephone care is a flourishing subspecialty of nursing requiring adaptations of bedside nursing skills and expertise in communication and telephone competencies. Telephone health care is more than "just answering the phone," even for the most experienced nurse. Knowledge of the unique skills, techniques, protocols, and legal considerations is essential in performing safe and accurate telephone triage.


Transparent and robust siloxane-based hybrid lamella film as a water vapor barrier coating.
Water vapor barriers are important in various application fields, such as food packaging and sealants in electronic devices. Polymer/clay composites are well-studied water vapor barrier materials, but their transparency and mechanical strength degrade with increasing clay loading. Herein, we demonstrate films with good water vapor barrier properties, high transparency, and mechanical/thermal stability. Water vapor barrier films were prepared by the solution crystallization of siloxane hybrid lamellae. The films consist of highly crystallized organic/inorganic hybrid lamellae, which provide high transparency, hardness, and thermal stability and inhibit the permeation of water vapor. The water permeability of a 6 μm thick hybrid film is comparable to that of a 200 μm thick silicon rubber film.


[Efforts of Lung Cancer Oncologists in the"With COVID-19"Era].
After the identification of the new coronavirus disease(COVID-19)in December 2019, it has spread rapidly around the world. The COVID-19 pandemic has forced medical systems to limit their services, promote telehealth, prolong visits to clinics, and postpone scheduled surgical operations. The mortality rate of COVID-19 in patients with lung cancer appears to be significantly higher than that of patients with other cancers. Medical care offered to patients with lung cancer should take into account the risk of COVID-19 associated with visits to clinics and treatments. This review outlines the efforts of lung cancer oncologists in the"With COVID-19"era based on the current evidence and statements from domestic and foreign academic societies and organizations.


Polymorphisms in DNA repair genes, medical exposure to ionizing radiation, and breast cancer risk.
An epidemiologic study was conducted to determine whether polymorphisms in DNA repair genes modify the association between breast cancer risk and exposure to ionizing radiation. Self-reported exposure to ionizing radiation from medical sources was evaluated as part of a population-based, case-control study of breast cancer in African-American (894 cases and 788 controls) and White (1,417 cases and 1,234 controls) women. Genotyping was conducted for polymorphisms in four genes involved in repair of radiation-induced DNA damage, the double-strand break repair pathway: X-ray cross-complementing group 3 (XRCC3) codon 241 Thr/Met, Nijmegen breakage syndrome 1 (NBS1) codon 185 Glu/Gln, X-ray cross-complementing group 2 (XRCC2) codon 188 Arg/His, and breast cancer susceptibility gene 2 (BRCH2) codon 372 Asn/His. Allele and genotype frequencies were not significantly different in cases compared with controls for all four genetic polymorphisms, and odds ratios for breast cancer were close to the null. Combining women with two, three, and four variant genotypes, a positive association was observed between breast cancer and number of lifetime mammograms (P(trend) < 0.0001). No association was observed among women with zero or one variant genotype (P = 0.86). Odds ratios for radiation treatments to the chest and number of lifetime chest X-rays were slightly elevated but not statistically significant among women with two to four variant genotypes. The study has several limitations, including inability to distinguish between diagnostic and screening mammograms or reliably classify prediagnostic mammograms and chest X-rays in cases. Prospective studies are needed to address whether common polymorphisms in DNA repair genes modify the effects of low-dose radiation exposure from medical sources.


A Cross-Sectional Analysis of American Insurance Coverage of Prominauris Otoplasty.
Prominent ears affect up to 5% of the population and can lead to social and psychological concerns at a critical time of social development. It can be addressed with an otoplasty, which is often considered a cosmetic procedure. The authors assessed insurance coverage of all indications of otoplasty and their medical necessity criteria. A cross-sectional analysis was conducted of 58 insurance policies for otoplasty. The insurance companies were selected based on their state enrolment and market share. A web-based search and telephone interviews were utilized to identify the policies. Medically necessary criteria were then abstracted from the publicly available policies. Of the 58 insurance policies assessed, 25 (43%) provide coverage of otoplasty. There were 2 indications for coverage: hearing loss (n = 20, 80%) and normal approximation (n = 14, 56%), which would encompass prominent ears. Normal approximation was a covered indication for significantly fewer insurers than hearing loss (56% versus 80%, P = 0.0013). Of all the otoplasty policies which covered normal approximation, 21% (n = 3) addressed protruding ears as an etiology. Prominent ears were not included in any policies which covered hearing loss. All policies inclusive of prominent ears required a protrusion of >20 mm from the temporal surface of the head (n = 3, 100%). There is a great discrepancy in insurance coverage of otoplasty. A greater proportion of policies cover hearing loss compared to normal approximation. The authors encourage plastic surgeons to advocate for the necessity and coverage of normal approximation by insurers.


Gluteal V-Y advancement fasciocutaneous flap for treatment of chronic pilonidal sinus disease.
Although pilonidal disease is quite common, controversy still exists about the treatment. The procedure should cure the patient, and allow speedy resumption of normal activities by reducing pain and disability. This retrospective study was conducted to evaluate our experience with the V-Y fasciocutaneous advancement flap and to review current publications about flap surgery for the treatment of sacrococcygeal pilonidal sinus. We describe the application of the fasciocutaneous V-Y advancement flap for reconstruction of defects after radical excision of recurrent pilonidal sinus in 11 cases. Primary and uneventful wound healing was achieved in all patients but two who developed minor wound breakdown. Large defects after excision can easily be closed using the V-Y advancement flap. This type of flap closure in selected cases offers tension-free, recurrence-free, and reliable skin coverage while flattening the natal cleft that predisposes to recurrences. Reliable flap closure reduces hospital stay, costs, as well as disability and time spent off work.


[The evaluation of lung function by using forced oscillation technique for children with asthma].
Lung function measurements are useful objective indices to monitor asthma control in children. Recently, a new forced oscillation technique machine called MostGraph (Chest Co. Ltd., Tokyo, Japan) has been developed to diagnose and monitor asthma. We assessed the utility of MostGraph in asthmatic children. We evaluated 66 well controlled asthmatic children (11±3 yrs). For each subject, we measured respiratory function using MostGraph and spirometry and assessed the relationship between the two indices. MostGraph measurements were significantly correlated with age and body height. R5 was remarkably associated with FEV1% by analyzing partial correlation that excluded the factor of height. In addition, R5-R20 and Fres were significantly related to FEV1% and MMF. Furthermore, R5-R20 and Fres were significantly associated with MMF through multiple regression analyses for MostGraph parameters, the height and spirometory parameters. We classified asthmatic children into two groups with 70% of V25 cut point. Group with V25 below 70% had higher scores for R5-R20, Fres and ALX, compared to group with V25 above 70%. MostGraph could be effectively used for the R5-R20 and Fres lung function measurements to assess asthma control in children. The results also suggested that R5-R20 and Fres might be parameters of small airway dysfunction.


Fragments of bovine serum albumin produced by limited proteolysis. Isolation and characterization of tryptic fragments.
Several fragments of bovine serum albumin have been isolated following limited tryptic hydrolysis and their positions then determined in the bovine serum albumin sequence published by J. R. Brown ((1975), Fed. Proc., Fed. Am. Soc. Exp. Biol. 34, 591). When bovine serum albumin was coupled to palmityl-aminoethylamino-agarose and digested with trypsin, two fragments were obtained: (a) peptide 115-184, containing the highly aromatic disulfide loop 3 of Brown's model, and (b) a larger fragment, residues 377-581, containing disulfide loops 7-9. This fragment constitutes the third of the three domains of the albumin molecule. From bovine serum albumin digested in solution, peptide 115-184 was again obtained, as well as (c) a 39,000-dalton fragment identified as residues 198-581, loops 4-9 of the second and third domains, but with a long, tryptophan-containing segment 204-238 missing from loop 4. The ability to isolate these fragments without cleaving disulfide bridges is partial confirmation of the proposed model of bovine serum albumin as a series of nine independent loops.


Thiophenol-mediated hydrogen atom abstraction: an efficient tin-free procedure for the preparation of cyclopentane derivatives.
[reaction: see text] An efficient procedure for running a cascade reaction involving 1,5-abstraction of a hydrogen atom followed by a radical cyclization is reported. Alkenyl radicals are generated from easily available terminal alkynes and thiophenol. This procedure eliminates the need of using the toxic tributyltin hydride and gives a greater amount of radical translocation products.


Improving productive performance, immunity, and health status of growing rabbits by using honey bee venom (Apis mellifera).
To investigate the effect of bee venom (BV) as a natural growth promotor on growing rabbits as an alternative to antibiotics, sixty 35-day-old Californian male rabbits with an average body weight of 584 ± 9 gm were randomly divided into five equal groups as follows: The 2nd group received drinking water supplied with 10 mg Oxytetracycline (OXT), while the 3rd, 4th, and 5th groups received 2, 4 and 8 mg bee venom (BV)/kg body weight/day in drinking water, and the first group was served as a control group. The growth performance features were positively impacted by adding BV (p ≤ 0.01) compared to the control, whereas LBW and BWG increased and FI reduced. Significantly improved carcass characteristics (p ≤ 0.01) as a result of the BV supplementation. Blood characteristics showed a significant reduction (p ≤ 0.01) in liver enzyme activities and Cholesterol, Triglycerides, and Low-density lipoproteins Cholesterol (LDL) as affected by BV treatment; inversely, total protein and globulin were significantly increased (p ≤ 0.01). Similarly, BV had a positive effect (p ≤ 0.01) on anti-oxidant status (Total anti-oxidant capacity (TAC), Glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT)). In contrast, the lipid peroxidation biomarker (Malondialdehyde (MDA)) was significantly decreased. The immunoglobulin (IgG and IgM) was significantly increased (p ≤ 0.01) by BV treatment. There was a positive effect of low BV levels on decreasing both cecum TBC and pathogenic bacterial count (Salmonella spp., E.coli spp., Proteus spp., and Clostridia spp.) that was significant (p ≤ 0.01). In conclusion, BV can be a natural growth promoter to enhance growth performance traits, immunological and anti-oxidative responses, and reduce pathogenic bacteria in the hindgut of growing rabbits.


Structure of Fungal α Mating Pheromone in Membrane Mimetics Suggests a Possible Role for Regulation at the Water-Membrane Interface.
Fusarium oxysporum is a highly destructive plant pathogen and an emerging pathogen of humans. Like other ascomycete fungi, F. oxysporum secretes α-pheromone, a small peptide that functions both as a chemoattractant and as a quorum-sensing signal. Three of the ten amino acid residues of α-pheromone are tryptophan, an amino acid whose sidechain has high affinity for lipid bilayers, suggesting a possible interaction with biological membranes. Here we tested the effect of different lipid environments on α-pheromone structure and function. Using spectroscopic and calorimetric approaches, we show that this peptide interacts with negatively charged model phospholipid vesicles. Fluorescence emission spectroscopy and nuclear magnetic resonance (NMR) measurements revealed a key role of the positively charged groups and Trp residues. Furthermore, NMR-based calculation of the 3D structure in the presence of micelles, formed by lipid surfactants, suggests that α-pheromone can establish an intramolecular disulfide bond between the two cysteine residues during interaction with membranes, but not in the absence of lipid mimetics. Remarkably, this oxidized version of α-pheromone lacks biological activity as a chemoattractant and quorum-sensing molecule. These results suggest the presence of a previously unidentified redox regulated control of α-pheromone activity at the surface of the plasma membrane that could influence the interaction with its cognate G-protein coupled receptor.


Remembering 1500 pictures: the right hemisphere remembers better than the left.
We hypothesized that the right hemisphere would be superior to the left hemisphere in remembering having seen a specific picture before, given its superiority in perceptually encoding specific aspects of visual form. A large set of pictures (N=1500) of animals, human faces, artifacts, landscapes, and art paintings were shown for 2s in central vision, or tachistoscopically (for 100ms) in each half visual field, to normal participants who were then tested 1-6 days later for their recognition. Images that were presented initially to the right hemisphere were better recognized than those presented to the left hemisphere. These results, obtained with participants with intact brains, large number of stimuli, and long retention delays, are consistent with previously described hemispheric differences in the memory of split-brain patients.


Disease and intolerability documentation in electronic patient records.
Documentation of diseases and intolerabilities in electronic patient records (EPRs) in pharmacies is needed to produce an alert in case a contraindicated medicine is prescribed. Limited research is available concerning EPRs in pharmacies. To study the prevalence and quality of documentation of diseases and intolerabilities in EPRs in a sample of Dutch community pharmacies. Each participating pharmacy (N = 79) collected data on one day in May 2003 for each patient enrolled into the study (N = 687) concerning demographics, drug use, and documentation of diseases and intolerabilities. In 57.4% of the EPRs, at least one disease and, in 7.9%, at least one intolerability was documented. Higher age, number of drugs used, and chronic disease score were associated with any documentation of a disease/intolerability in the EPR. The highest sensitivity scores (completeness) were found for diabetes (84.7%), asthma/chronic obstructive pulmonary disease (strict definition: 75.9%), and hypothyroidism (75.0%). Rather low values were found for prostatic hyperplasia (55.6%) and heart failure (29.4%). The positive predictive value (reliability) was high for hypothyroidism (100%) and diabetes (87.1%). In a selection of Dutch pharmacies, at least one documented disease and/or intolerability was found in the EPR of almost 60% of the patients. Certain diseases were documented to a relatively high degree; others had poorer levels of documentation. For optimal surveillance of drug-disease interactions in pharmacies, the frequency and quality of disease and intolerability documentation need further improvement.


Costs of Care for Operative and Non-Operative Management of Emergency General Surgery Conditions.
Many emergency general surgery (EGS) conditions can be managed operatively or non-operatively, with outcomes that vary by diagnosis. We hypothesized that operative management would lead to higher in-hospital costs but to cost savings over time. Emergency general surgery conditions account for $28 billion in healthcare costs in the US annually. Compared to scheduled surgery, patients who undergo emergency surgery are at increased risk of complications, readmissions, and death, with accompanying costs of care that are up to 50% higher than elective surgery. Our prior work demonstrated that operative management had variable impacts on clinical outcomes depending on EGS condition. This was a nationwide, retrospective study using fee-for-service Medicare claims data. We included patients ≥ 65.5 years of age with a principal diagnosis for an EGS condition, 7/1/2015-6/30/2018. EGS conditions were categorized as: colorectal, general abdominal, hepatopancreaticobiliary, intestinal obstruction, and upper gastrointestinal. We used near-far matching with a preference-based instrumental variable to adjust for confounding and selection bias. Outcomes included Medicare payments for the index hospitalization and at 30, 90, and 180 days. Of 507,677 patients, 30.6% received an operation. For hepatopancreaticobiliary conditions, costs for operative management were initially higher but became equivalent at 90 and 180 days. For all others, operative management was associated with higher inpatient costs which persisted, though narrowed, over time. Out-of-pocket costs were nearly equivalent for operative and non-operative management. Compared to non-operative management, costs were higher or equivalent for operative management of EGS conditions through 180 days, which could impact decision-making for clinicians, patients, and health systems in situations where clinical outcomes are similar.


[Tetanus. Apropos a case].
The authors report a case of tetanus in a 19 months infant who has only received BCG. After a four days period during which two laryngeal spasms occurred, the infant presents a generalized tetanus. The outcome was favorable with specific serotherapy myorelaxants and assisted ventilation of four weeks duration.


Generating 3D molecules conditional on receptor binding sites with deep generative models.
The goal of structure-based drug discovery is to find small molecules that bind to a given target protein. Deep learning has been used to generate drug-like molecules with certain cheminformatic properties, but has not yet been applied to generating 3D molecules predicted to bind to proteins by sampling the conditional distribution of protein-ligand binding interactions. In this work, we describe for the first time a deep learning system for generating 3D molecular structures conditioned on a receptor binding site. We approach the problem using a conditional variational autoencoder trained on an atomic density grid representation of cross-docked protein-ligand structures. We apply atom fitting and bond inference procedures to construct valid molecular conformations from generated atomic densities. We evaluate the properties of the generated molecules and demonstrate that they change significantly when conditioned on mutated receptors. We also explore the latent space learned by our generative model using sampling and interpolation techniques. This work opens the door for end-to-end prediction of stable bioactive molecules from protein structures with deep learning.


Are all antidepressants the same? The consumer has a point.
Although a large variety of antidepressants agents (AD) with different mechanisms of action are available, no significant differences in efficacy and safety have been shown. However, there have been few attempts to incorporate data on subjective experiences under different AD. We conducted a qualitative and quantitative analysis of the posts from the website www.askapatient.com from different AD. We reviewed a random sample of 1000 posts. After applying the inclusion and exclusion criteria, we included a final sample of 450 posts, 50 on each of the most used AD: sertraline, citalopram, paroxetine, escitalopram, fluoxetine, venlafaxine, duloxetine, mirtazapine, and bupropion. Bupropion, citalopram, and venlafaxine had the higher overall satisfaction ratings. Sertraline, paroxetine, and fluoxetine had high reports of emotional blunting, while bupropion very few. Overall satisfaction with AD treatment was inversely associated with the presence of the following side-effects: suicidality, irritability, emotional blunting, cognitive disturbances, and withdrawal symptoms. After adjusting for confounders, only emotional blunting was shown to be more frequently reported by users of serotonergic agents, as compared to non-serotoninergic agents. This research points out that the subjective experience of patients under treatment should be taken into consideration when selecting an AD as differences between agents were evident. In contrast to the more frequent treatment decisions, users might prefer receiving a non-serotoninergic agent over a serotonergic one due to their lower propensity to produce emotional blunting.


Border control: selectivity of chloroplast protein import and regulation at the TOC-complex.
Plants have evolved complex and sophisticated molecular mechanisms to regulate their development and adapt to their surrounding environment. Particularly the development of their specific organelles, chloroplasts and other plastid-types, is finely tuned in accordance with the metabolic needs of the cell. The normal development and functioning of plastids require import of particular subsets of nuclear encoded proteins. Most preproteins contain a cleavable sequence at their N terminal (transit peptide) serving as a signal for targeting to the organelle and recognition by the translocation machinery TOC-TIC (translocon of outer membrane complex-translocon of inner membrane complex) spanning the dual membrane envelope. The plastid proteome needs constant remodeling in response to developmental and environmental factors. Therefore selective regulation of preprotein import plays a crucial role in plant development. In this review we describe the diversity of transit peptides and TOC receptor complexes, and summarize the current knowledge and potential directions for future research concerning regulation of the different Toc isoforms.


Endometrial fluid collection in women with PCOS undergoing ovarian stimulation for IVF. A report of four cases.
The presence of endometrial fluid collections' developing during ovarian-stimulation was previously reported to occur in women with hydrosalpinx. We report on the occurrence of endometrial fluid collections in four women with polycystic ovary syndrome (PCOS) undergoing ovarian stimulation for in vitro fertilization. Four women developed endometrial fluid collections during ovarian stimulation. These fluid collections were noted as early as day 5 of stimulation. The reproductive outcome when fluid collections were noted on the day of human chorionic gonadotropin (hCG) or of embryo transfer (ET) was poor. One of three women with fluid collection on the day of hCG conceived but had a missed abortion. One patient with fluid on the day of ET failed to conceive. Three of four patients who underwent repeat cycles conceived when no fluid collections were seen on day of hCG or ET. Abnormal endometrial milieu could be an underlying defect in some women with PCOS and chronic anovulation who fail to conceive with ovulation-induction agents. This is the first report of endometrial fluid collections in patients with PCOS in the absence of hydrosalpinx. Continuous monitoring of the endometrial lining during ovulation induction is mandatory to rule out any abnormality in endometrial development. Cryopreserving all embryos may be considering in cycles with fluid collections noted on the day hCG or ET.


[The algorithms of acute phase treatment for patients with Kawasaki disease].
Approximately one decade has passed when the original version of "Guidelines for Medi cal Treatment of Acute Kawasaki Disease" was published. Since then, many clinical stud ies have investigated and new evidences regarding diagnosis and acute phase treatment have been piled up. Based upon the background, Research Committee of the Japanese Society of Pediatric Cardiology and Cardiac Surgery revised the guideline in December 2012. The revised guideline proposed new therapeutic algorithm for acute Kawasaki disease patients. The present review overviews the revised guideline especially focused on the algorithm, and explains how to treat acute phase Kawasaki disease patients.


Detection of HEV antigen as a novel marker for the diagnosis of hepatitis E.
Infection with hepatitis E virus (HEV) may be diagnosed by the presence of HEV RNA or anti-HEV antibodies. An enzyme immunoassay (EIA) was developed for the detection of antigen. Twenty-four monoclonal antibodies (mAbs) were produced. An indirect sandwich EIA was developed to detect HEV antigen using a combination of three mAbs as coating antibodies. Approximately 44.6% (33/74), 28.6% (50/175), and none (0/27) of sera positive for anti-HEV IgM alone, both anti-HEV IgM and IgG, and anti-HEV IgG alone also were positive for HEV antigen using this EIA. Forty-two HEV antibody-positive sera were tested for HEV RNA and antigen in parallel and the concordance was 81.0% (34/42). All PCR products were found to belong to HEV genotype 4. In order to evaluate the temporal relationship between HEV antigen positivity and HEV RNA, anti-HEV IgG and IgM, and ALT concentrations, macaques were infected with HEV genotypes 1 and 4 and serial samples were collected. The results showed that the antigen EIA can detect the capsid proteins of both genotypes. HEV antigen was detectable prior to ALT elevation and the appearance of anti-HEV antibodies in the infected monkeys and lasted for several weeks in all cases. HEV antigen became detectable in the serum at almost the same time as HEV RNA in feces but persisted for 4 weeks less than HEV RNA. This assay should be valuable for the diagnosis of acute hepatitis E, particularly in the window period prior to seroconversion to anti-HEV.


Vascular Smooth Muscle Cells Stimulate Platelets and Facilitate Thrombus Formation through Platelet CLEC-2: Implications in Atherothrombosis.
The platelet receptor CLEC-2 is involved in thrombosis/hemostasis, but its ligand, podoplanin, is expressed only in advanced atherosclerotic lesions. We investigated CLEC-2 ligands in vessel walls. Recombinant CLEC-2 bound to early atherosclerotic lesions and normal arterial walls, co-localizing with vascular smooth muscle cells (VSMCs). Flow cytometry and immunocytochemistry showed that recombinant CLEC-2, but not an anti-podoplanin antibody, bound to VSMCs, suggesting that CLEC-2 ligands other than podoplanin are present in VSMCs. VSMCs stimulated platelet granule release and supported thrombus formation under flow, dependent on CLEC-2. The time to occlusion in a FeCl3-induced animal thrombosis model was significantly prolonged in the absence of CLEC-2. Because the internal elastic lamina was lacerated in our FeCl3-induced model, we assume that the interaction between CLEC-2 and its ligands in VSMCs induces thrombus formation. Protein arrays and Biacore analysis were used to identify S100A13 as a CLEC-2 ligand in VSMCs. However, S100A13 is not responsible for the above-described VSMC-induced platelet activation, because S100A13 is not expressed on the surface of normal VSMCs. S100A13 was released upon oxidative stress and expressed in the luminal area of atherosclerotic lesions. Suspended S100A13 did not activate platelets, but immobilized S100A13 significantly increased thrombus formation on collagen-coated surfaces. Taken together, we proposed that VSMCs stimulate platelets through CLEC-2, possibly leading to thrombus formation after plaque erosion and stent implantation, where VSMCs are exposed to blood flow. Furthermore, we identified S100A13 as one of the ligands on VSMCs.


Radiology medical student education: an outcome-based survey of PGY-1 residents.
Postgraduate year (PGY)-1 residents are frequently required to order imaging studies and make preliminary interpretations on them. This study determines whether PGY-1 residents feel their radiology education in medical school sufficiently trained them for the clinical responsibilities of internship. This multicenter, institutional review board-approved survey asked PGY-1 trainees three categories of questions: 1) extent of medical school training for ordering and interpreting imaging studies, 2) confidence levels in ordering appropriate imaging studies and making common/emergent diagnoses, and 3) rating the importance of radiologic interpretation by interns. Respondents also submitted ideas for medical school teaching topics deemed most useful for interns. A total of 175 questionnaires were returned with good representation across specialties. Although 63.7% of interns were frequently asked to independently preview radiology studies, 12.6% received no formal radiology training in medical school. Participants rated chest radiographs as the most important study for interns to competently interpret (93.4% reporting very or extremely important). However, only 60.2% of interns reported high confidence in recognizing common/emergent pulmonary findings, and 56.3% for evaluating line and tube position. With regard to ordering imaging studies, 81.0% had never used or never heard of the American College of Radiology Appropriateness Criteria®. Only 33.1% had high confidence in knowing when to order oral/intravenous contrast. Similar low percentages had high confidence identifying and premedicating contrast allergies (36.4%) and knowing risk factors of nephrogenic systemic fibrosis (13.2%). PGY-1 residents feel that medical school curriculum emphasizing interpretation of chest radiographs and ordering appropriate imaging studies would better prepare students for the responsibilities of internship.


Determination of propagation model matrix in generalized cross-correlation based inverse model for broadband acoustic source localization.
The generalized cross-correlation (GCC) based inverse model is a promising time domain localization technique for a broadband acoustic source. Its performance is affected by the temporal width threshold of the propagation model matrix. The appropriate threshold should vary with focus distance, array geometry, and array size, but there is still a lack of uniform and effective methods to determine it. To solve this issue and perfect the technique, a method is proposed based on the cumulative probability of all differences of time delay estimation between the focus point and the microphone pair. Further, an alternative propagation model matrix is derived, which circumvents the threshold. Both proposed methods are effective under different simulation and experimental configurations, with strong stability and adaptability to focus distance, array geometry, and array size. The GCC based inverse model with either proposed method not only enjoys satisfactory source localization performance, including narrow mainlobes, few spurious sources, and highlighted source positions, but also can correctly estimate the sound level, which is comparable to that with the preset appropriate temporal width threshold. In terms of the computational time, the inverse model with the latter proposed method outperforms that with the former one.


DG-RAR for the treatment of symptomatic grade III and grade IV haemorrhoids: a 12-month multi-centre, prospective observational study.
Ultrasound-guided techniques represent a new treatment option in the treatment of haemorrhoids. Doppler-guided haemorrhoidal artery ligation (DG-HAL) proved efficacious in early haemorrhoidal disease, but lacks efficacy for stages III/IV. For these patients, haemorrhoidal artery ligation (HAL) has been combined with a running suture to reduce prolapsing haemorrhoidal tissue (recto-anal repair (RAR)). A prospective observational study was conducted in 184 patients with grade III (58 %) or grade IV (42 %) haemorrhoids in seven coloproctological centres. Primary endpoints were the recurrence of symptoms and need of further treatment (medical or surgical). Post-operative complications were seen in 8 % of patients. After a follow-up of 3 months, 91 % of patients were free of symptoms and 91 % of patients were satisfied with the result. After a follow-up of 12 months, 89 % of patients were free of symptoms and 88 % were satisfied with the result. Nineteen per cent of patients received further medical or surgical treatment. Doppler-guided recto-anal repair (DG-RAR) proves to be an effective treatment option for the treatment of advanced haemorrhoidal disease that shows equal results to other established treatment options.


Dopamine D4 receptor gene and religious affiliation correlate with dictator game altruism in males and not females: evidence for gender-sensitive gene × culture interaction.
On a large sample of 2288 Han Chinese undergraduates, we investigated how religion and DRD4 are related to human altruistic giving behavior as measured with the Andreoni-Miller Dictator Game. This game enables us to clearly specify (non-)selfishness, efficiency, and fairness motives for sharing. Participants were further classified into religious categories (Christian, Buddhist-Tao, and No Religion) based on self-reports, and genotyped for the dopamine D4 receptor (DRD4) gene exon III VNTR. Our analysis revealed a significant interaction between religion and DRD4 correlated with giving behavior solely among males: Whereas no significant association between religion and sharing decisions was observed in the majority 4R/4R genotype group, a significant difference in giving behavior between Christian and non-Christian males was seen in the non-4R/4R group, with Christian men being overall more altruistic (less selfish and fairer) than non-Christian men. These results support the vantage sensitivity hypothesis regarding DRD4 that the non-4R/4R "susceptibility" genotype is more responsive to a positive environment provided by some religions.


HPV Knowledge and Attitudes Among American Indian and Alaska Native Health and STEM Conference Attendees.
American Indian and Alaska Native women had approximately twice the incidence of cervical cancer as white women. Preventive measures for cervical cancer rely on screening and HPV vaccination. However, vaccine series completion and catch-up vaccinations for eligible adults are low across all racial/ethnic groups. Therefore, the aim of this study was to identify gaps in knowledge and evaluate the attitudes toward HPV and the vaccine among AIANs with various levels of training in the STEM and health-related fields. A survey was used to collect data from audience members at two national conferences geared towards American Indian and Alaska Natives in health and STEM fields in September 2017. A vignette study was administered via a live electronic poll to test knowledge (true/false questions), attitudes, and to collect demographic information. Respondents self-identified as primarily American Indian and Alaska Native (74%), pursuing or completed a graduate degree (67%), and female (85%). Most respondents (86%) were aware of HPV-associated cancer in men. However, most (48-90%) answered incorrectly to detailed true/false statements about HPV and available vaccines. After educational information was provided, opinions collected via vignettes highlighted mainly positive attitudes toward vaccination; specifically, that vaccines are safe and all eligible community members should be vaccinated (75% and 84%, respectively). We observed that our respondents with higher educational attainment still lacked accurate knowledge pertaining to HPV and the vaccine. Overall, continued education about HPV and the vaccine is needed across all levels of education including American Indian and Alaska Native community members and health professionals.


Different Degree Centrality Changes in the Brain after Acupuncture on Contralateral or Ipsilateral Acupoint in Patients with Chronic Shoulder Pain: A Resting-State fMRI Study.
Chronic shoulder pain (CSP) is the third most common musculoskeletal problem. For maximum treatment effectiveness, most acupuncturists usually choose acupoint in the nonpainful side, to alleviate pain or improve shoulder function. This method is named opposite needling, which means acupuncture points on the right side are selected for diseases on the left side and vice versa. However, the underlying neural mechanisms related to treatment are currently unclear. The purpose of this study was to determine whether different mechanisms were observed with contralateral and ipsilateral acupuncture at Tiaokou (ST 38) in patients with unilateral CSP. Twenty-four patients were randomized to the contralateral acupuncture group (contra-group) and the ipsilateral acupuncture group (ipsi-group). The patients received one acupuncture treatment session at ST 38 on the nonpainful or painful sides, respectively. Before and after acupuncture treatment, they underwent functional magnetic resonance scanning. The treatment-related changes in degree centrality (DC) maps were compared between the two groups. We found alleviated pain and improved shoulder function in both groups, but better shoulder functional improvement was observed in the contra-group. Increased DC in the anterior/paracingulate cortex and decreased DC in bilateral postcentral gyri were found in the contra-group, while decreased DC in the bilateral cerebellum and right thalamus was observed in the ipsi-group. Furthermore, the DC value in the bilateral anterior/paracingulate cortex was positively correlated with the treatment-related change in the Constant-Murley score. The current study reveals different changes of DC patterns after acupuncture at contralateral or ipsilateral ST 38 in patients with CSP. Our findings support the hypothesis of acupoint specificity and provide the evidence for acupuncturists to select acupoints for CSP.


Immobilization of Multivalent Titanium Cations on Magnetic Composite Microspheres for Highly Efficient DNA Extraction and Amplification.
Magnetic-assisted DNA testing technology has attracted much attention in genetics, clinical diagnostics, environmental microbiology, and molecular biology. However, achieving satisfying DNA adsorption and desorption efficiency in real samples is still a big challenge. In this paper, a new kind of high-quality magnetic composite microsphere of MM@PGMA-PA-Ti4+ was designed and prepared for DNA extraction and detection based on the strong interaction of Ti4+ and phosphate groups. By taking the advantages of high magnetic susceptibility and high Ti4+ content, the MM@PGMA-PA-Ti4+ microspheres possessed remarkable extraction capacity for mimic biological samples (salmon sperm specimens) with saturated loadings up to 533.0 mg/g. When the DNA feeding amount was 100 μg and the MM@PGMA-PA-Ti4+ dosage was 1 mg, the adsorption and desorption efficiencies were 80 and 90%, respectively. The kinetic and equilibrium extraction data were found to fit well with the pseudo-second-order model and Freundlich isotherm model. Furthermore, the MM@PGMA-PA-Ti4+ microspheres were successfully employed for DNA extraction from mouse epithelial-like fibroblasts. The extraction ability (84 ± 4 μg/mg) and DNA purity were superior to the comparative commercial spin kits, as evaluated by electrophoresis assays and qPCR analysis. The experimental results suggest that the MM@PGMA-PA-Ti4+ microspheres possess great potential as an adsorbent for DNA purification from complex biological samples.


Texture analysis of parasitological liver fibrosis images.
Liver fibrosis accurate staging is vital to define the state of the Schistosomiasis disease for further treatment. The present work analyzed the microscopic liver images to identify and to differentiate between healthy, cellular, fibrocellular, and fibrous liver pathologies by proposing a fast, robust, and highly discriminative method based on texture analysis. The multiclass classification based on the "one-versus- all" method that built a voting rule approach to classify the liver images based on the liver state. Specifically, quantitative parameters, such as the anisotropy and laminarity are proposed based on the relative orientation of the pixel pairs in a global and local coherence of gradient vectors approach. Analysis of the tissue texture data using both gradient vector and gradient angle co-occurrence matrix approaches facilitated more definitive identification of the abnormal tissue. The experimental results established that the local anisotropy based texture measures are appropriated for the microtexture analysis in order to discriminate between pathologies. Macrotexture description using the global features provided only integral anisotropy coefficient that has a confidence level similar to those provided by the local feature.


[The new narcotic drug law and its effects on the panorama change of the drug scene of the Aachen border district].
The situation in the region of Aix la Chapelle with its borders towards The Netherlands and Belgium has presented us with increasing problems in drug and narcotic delinquency during recent years. Because of the revised law on narcotic drugs in 1982 and recent decisions by the German Federal Supreme Court, forensic toxicologists are expected not only to define drugs qualitatively as well as quantitatively, but also to provide expertise on problems of effective doses, pharmacokinetics, toxicity and tolerance development with various narcotic drugs. Based on our own experience in this special forensic field, as well as on the data compiled by investigation authorities, our analytical findings are presented with regard to toxicological interpretation and the legal consequences.


Korean Solar Salt Ameliorates Colon Carcinogenesis in an AOM/DSS-Induced C57BL/6 Mouse Model.
The effects of Korean solar salt on an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon cancer C57BL/6 mouse model were studied. Korean solar salt samples (SS-S, solar salt from S salt field; SS-Yb, solar salt from Yb salt field), nine-time-baked bamboo salt (BS-9x, made from SS-Yb), purified salt (PS), and SS-G (solar salt from Guérande, France) were orally administered at a concentration of 1% during AOM/DSS colon cancer induction, and compared for their protective effects during colon carcinogenesis in C57BL/6 mice. SS-S and SS-Yb suppressed colon length shortening and tumor counts in mouse colons. Histological evaluation by hematoxylin and eosin staining also revealed suppression of tumorigenesis by SS-S. Conversely, PS and SS-G did not show a similar suppressive efficacy as Korean solar salt. SS-S and SS-Yb promoted colon mRNA expression of an apoptosis-related factor and cell-cycle-related gene and suppressed pro-inflammatory factor. SS-Yb baked into BS-9x further promoted these anti-carcinogenic efficacies. Taken together, the results indicate that Korean solar salt, especially SS-S and SS-Yb, exhibited anti-cancer activity by modulating apoptosis- and inflammation-related gene expression during colon carcinogenesis in mice, and bamboo salt baked from SS-Yb showed enhanced anti-cancer functionality.


Escherichia coli O 157:H7-associated hemolytic-uremic syndrome after ingestion of contaminated hamburgers.
We conducted a retrospective analysis of 37 children with Escherichia coli O157:H7-associated hemolytic-uremic syndrome. The infection was traced to contaminated hamburgers at a fast-food restaurant chain. Within 5 days of the first confirmed case, the Washington State Department of Health identified the source and interrupted transmission of infection. Ninety-five percent of the children initially had severe hemorrhagic colitis. Nineteen patients (51%) had significant extrarenal abnormalities, including pancreatitis, colonic necrosis, glucose intolerance, coma, stroke, seizures, myocardial dysfunction, pericardial effusions, adult respiratory disease syndrome, and pleural effusions. Three deaths occurred, each in children with severe multisystem disease. At follow-up two children have significant impairment of renal function (glomerular filtration rate < 80 ml/min/per 1.73 Hm2); both of these children have a normal serum creatinine concentration. Hemolytic-uremic syndrome is the most common cause of acute renal failure in children, and this experience emphasizes the systemic nature of this disease. Clinicians should anticipate that multisystem involvement may occur in these patients, necessitating acute intervention or chronic follow-up. This outbreak of Hemolytic-uremic syndrome also highlights the microbiologic hazards of inadequately prepared food and emphasizes the importance of public health intervention in controlling Hemolytic-uremic syndrome.


Correlation of cag-A serological status with histological parameters of chronic gastritis among dyspeptic patients in south western Nigeria.
The aim of this study was to determine the sero-prevalence of Cag-A strains of Helicobacter pylori in both dyspeptic and non-dyspeptic individuals and also correlate the serological status of Gag-A strain of H. pylori with the various graded histological variables of chronic gastritis in the dyspeptic patients. Using helicobacter p120 Cag-A enzyme linked immunosorbent assay, Cag-A serology test was carried out on 65 dyspeptic patients and 65 age and sex matched non-dyspeptic controls. The gastric biopsies of the patients were also histologically examined to ascertain the presence, nature and degree of the following histological variables of gastritis: colonisation by H. pylori; inflammation, intestinal metaplasia and mucosal atrophy. The CagA serological status was then correlated with the graded variables. A prevalence of 46.2% and 58.8% seropositivity for Cag-A strain of H. pylori was found among dyspeptic patients and control individuals respectively. Cag-A seropositive patients accounted for nine(81.8%) of the 11 cases with moderate to severe activity and 75% of both cases with mucosal atrophy and cases with intestinal metaplasia. Infection with Cag-A positive Helicobacter pylori was equally prevalent among both dyspeptic patients and control subjects studied. CagA seropositivity, however, appeared to be associated with higher inflammatory activity in the mucosa of patients with chronic gastritis and may be associated with intestinal metaplasia and mucosal atrophy in H. pylori-induced chronic gastritis.


Boundary displacement measurements using multi-energy soft x-rays.
The Multi-Energy Soft X-ray (ME-SXR) system on NSTX provides radial profiles of soft X-ray emission, measured through a set of filters with varying thickness, which have been used to reconstruct the electron temperature on fast time scales (∼10 kHz). In addition to this functionality, here we show that the ME-SXR system can be used to measure the boundary displacement of the NSTX plasma with a few mm spatial resolution during magnetohydrodyamic (MHD) activity. Boundary displacement measurements can serve to inform theoretical predictions of neoclassical toroidal viscosity, and will be used to investigate other edge phenomena on NSTX-U. For example, boundary measurements using filtered SXR measurements can provide information on pedestal steepness and dynamic evolution leading up to and during edge localized modes (ELMs). Future applications include an assessment of a simplified, filtered SXR edge detection system as well as its suitability for real-time non-magnetic boundary feedback for ELMs, MHD, and equilibrium position control.


Chitinase-resistant hydrophilic symbiotic factors secreted by Frankia activate both Ca(2+) spiking and NIN gene expression in the actinorhizal plant Casuarina glauca.
Although it is now well-established that decorated lipo-chitooligosaccharide Nod factors are the key rhizobial signals which initiate infection/nodulation in host legume species, the identity of the equivalent microbial signaling molecules in the Frankia/actinorhizal association remains elusive. With the objective of identifying Frankia symbiotic factors we present a novel approach based on both molecular and cellular pre-infection reporters expressed in the model actinorhizal species Casuarina glauca. By introducing the nuclear-localized cameleon Nup-YC2.1 into Casuarina glauca we show that cell-free culture supernatants of the compatible Frankia CcI3 strain are able to elicit sustained high frequency Ca(2+) spiking in host root hairs. Furthermore, an excellent correlation exists between the triggering of nuclear Ca(2+) spiking and the transcriptional activation of the ProCgNIN:GFP reporter as a function of the Frankia strain tested. These two pre-infection symbiotic responses have been used in combination to show that the signal molecules present in the Frankia CcI3 supernatant are hydrophilic, of low molecular weight and resistant to chitinase degradation. In conclusion, the biologically active symbiotic signals secreted by Frankia appear to be chemically distinct from the currently known chitin-based rhizobial/arbuscular mycorrhizal signaling molecules. Convenient bioassays in Casuarina glauca are now available for their full characterization.


Dopamine and its metabolites in human tears.
Dopamine is known to stimulate ion transport in the corneal epithelium. Since epithelium is in contact with tears, we searched for dopamine and its metabolites in tears. Twenty normal subjects participated in this study. Twenty microliters of tears were collected in capillary tubes after trigeminal stimulation and immediately analyzed using high-performance liquid chromatography with electrochemical detection. Dopamine and two of its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were identified and measured. The mean concentration of dopamine was 8.9 +/- 5.1 ng/ml; DOPAC, 2.2 +/- 1.6 ng/ml; and HVA, 0.55 +/- 0.4 ng/ml. These results permit us to suggest that dopamine is deaminated by monoamine oxidase, then methylated by catechol-O-methyltransferase and that catabolism occurs in the lacrimal gland and perhaps in corneal epithelium. Finally, part of the dopamine involved in ion transport may come from tears.


Symptom Experience and Perceived Health Status of People With Long COVID in Thailand.
Despite the World Health Organization declaring COVID-19 no longer a public health emergency, reports of long COVID persist globally, raising concerns about its impact on individuals. This retrospective study aimed to explore the symptom experiences of individuals with long COVID-19 and examine the relationship between those experiences and perceived negative health status in Thailand. The study focused on individuals with moderate to severe COVID-19 infections. Between July 3, 2022 and December 1, 2022, we conducted telephone interviews with 86 individuals who tested positive for SARS-CoV-2 and received outpatient care in Bangkok. The COVID-19 Yorkshire Rehabilitation Screening was utilized to measure symptom occurrence, duration, severity, and health status on an 11-point numerical rating scale from 0 (none or excellent) to 10 (the worst). A Spearman rank correlation was used to analyze the relationships between long COVID symptoms and negative perception of health status. Among the participants, 75.6% had long COVID, with a median of three symptoms lasting for a median duration of 5.6 months. Difficulties in performing daily activities were most common, reported by 50.8% of participants. The majority (80.0%) experienced itching, headache, cognition, muscle pain, continence, and sleeping problem for 6 months. Loss of taste was the most severe symptom, with a mean severity rating of 8.8. There were significant positive relations between a negative perception of health status and multiple symptoms, symptom severity, functional disability, and additional symptoms. Individuals with moderate to severe COVID-19 infection who experienced long COVID had poorer perceived health status. To effectively manage and improve the health status of individuals with long COVID, nurses should provide follow-up care, assess not only the occurrence of symptoms but also their duration and severity, and evaluate performance outcomes.


Contribution of NADH dehydrogenase subunit I and cytochrome C oxidase subunit I sequences toward identifying a case of human coenuriasis in France.
Coenuriasis is a parasitic disease induced by larval taeniid tapeworms that is rarely observed in humans. In December 2005, a case was diagnosed in Nancy, France, after surgical excision of a cyst on a 24-yr-old woman returning from the Côte d'Ivoire. Morphological and epidemiological criteria suggested that the infection was due to Taenia serialis. Molecular analysis of NADH dehydrogenase subunit I (NDI) and cytochrome c oxidase subunit I (COI) sequences was also in favor of T. serialis identification, but the absence of available genetic data on T. brauni and T. glomeratus and the small number of published sequences for T. serialis and T. multiceps must be considered with caution. The NDI partial sequences presented more variations within species of Taenia than the COI sequences, which make them more useful targets for species identification and analysis of intraspecific polymorphisms. The present study points to the usefulness of molecular biology tools to help make up for the shortcomings of the commonplace parasitological diagnosis for coenuriasis.


A clinical audit to assess the efficacy of the Coolsense® Pain Numbing Applicator for intravenous cannulation in children.
The Coolsense® device is a topical applicator that is used to anaesthetise the skin before a painful procedure. It is a handheld device with a temperature-controlled head that acts on application, without chemicals, to cool and anaesthetise the site of injection. This prospective observational audit of 100 children and adolescents aged six to 18 years studied the analgesic efficacy and patient and carer satisfaction rating of the device during intravenous cannulation and complications arising from its use. The audit demonstrated effective skin analgesia for intravenous cannulation in children and adolescents. Ninety-four percent of patients rated the pain during cannulation as less than or equal to three on a numerical pain rating scale of zero to ten. Patient and carer satisfaction with the device and cannulation success rates were high; 66% of patients and 82% of carers 'really liked' the device and 28% of patients and 12% of carers 'liked' it. Ninety-five percent of patients were cannulated on the first attempt. The incidence of complications using the device was low. The Coolsense device appears to be a useful tool that provides effective analgesia for intravenous cannulation in children with minimal complications. Comparative studies with topical local anaesthesia creams are warranted.


MANAGING THYROID TUMORS DIAGNOSED AS NON-INVASIVE FOLLICULAR TUMOR WITH PAPILLARY LIKE NUCLEAR FEATURES (NIFTP).
This commentary summarizes the history and reclassification of noninvasive follicular thyroid tumor with papillary like nuclei (NIFTP). The salient histopathologic features, which are based on immunohistochemical and molecular profiles and serve as inclusion and exclusion criteria are reviewed. The authors also provide their own point of view regarding the practical issues and possible concerns that may be raised by both clinicians and patients based on the diagnosis of NIFTP.


Regulatory T cells in skin.
Foxp3+ CD4+ regulatory T (Treg) cells are a subset of immune cells that function to regulate tissue inflammation. Skin is one of the largest organs and is home to a large proportion of the body's Treg cells. However, relative to other tissues (such as the spleen and gastrointestinal tract) the function of Treg cells in skin is less well defined. Here, we review our understanding of how Treg cells migrate to skin and the cellular and molecular pathways required for their maintenance in this tissue. In addition, we outline what is known about the specialized functions of Treg cells in skin. Namely, the orchestration of stem cell-mediated hair follicle regeneration, augmentation of wound healing, and promoting adaptive immune tolerance to skin commensal microbes. A comprehensive understanding of the biology of skin Treg cells may lead to novel therapeutic approaches that preferentially target these cells to treat cutaneous autoimmunity, skin cancers and disorders of skin regeneration.


Disease spread in age structured populations with maternal age effects.
Fundamental ecological processes, such as extrinsic mortality, determine population age structure. This influences disease spread when individuals of different ages differ in susceptibility or when maternal age determines offspring susceptibility. We show that Daphnia magna offspring born to young mothers are more susceptible than those born to older mothers, and consider this alongside previous observations that susceptibility declines with age in this system. We used a susceptible-infected compartmental model to investigate how age-specific susceptibility and maternal age effects on offspring susceptibility interact with demographic factors affecting disease spread. Our results show a scenario where an increase in extrinsic mortality drives an increase in transmission potential. Thus, we identify a realistic context in which age effects and maternal effects produce conditions favouring disease transmission.


The role of geriatricians and family practitioners in the treatment of overactive bladder and incontinence.
Although the prevalence of overactive bladder (OAB) and that of its symptoms (urinary urge incontinence, urgency, and frequency) increase with age, these conditions are not necessarily normal consequences of aging. Patients who present with urinary symptoms should be evaluated and treated, whether they are living on their own or in a residential, assisted-care, or long-term-care environment. Effective treatment for OAB and urinary incontinence (UI) is available and improves quality of life for the elderly. The primary care physician and geriatrician can accomplish a basic evaluation for UI using a systematic approach, as detailed in the following pages.


Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus.
Acute diarrhoea is a serious cause of infant morbidity and mortality, and the development of preventive measures remains an important goal. Bifidobacteria (which constitute the predominant intestinal flora of breastfed infants), as well as other lactic-acid-producing organisms such as Streptococcus thermophilus, are thought to have a protective effect against acute diarrhoeal disease. However, their efficacy has not been assessed in controlled trials. In a double-blind, placebo-controlled trial, infants aged 5-24 months who were admitted to a chronic medical care hospital were randomised to receive a standard infant formula or the same formula supplemented with Bifidobacterium bifidum and S thermophilus. Patients were evaluated daily for occurrence of diarrhoea, and faecal samples, obtained weekly, were analysed for rotavirus antigen by enzyme immunoassay. Faecal samples were also obtained during an episode of diarrhoea for virological and bacteriological analyses. 55 subjects were evaluated for a total of 4447 patient-days during 17 months. 8 (31%) of the 26 patients who received the control formula and 2 (7%) of 29 who received the supplemented formula developed diarrhoea during the course of the study (p = 0.035, Fisher's exact test, two-tailed). 10 (39%) of the subjects who received the control formula and 3 (10%) of those who received the supplemented formula shed rotavirus at some time during the study (p = 0.025). The supplementation of infant formula with B bifidum and S thermophilus can reduce the incidence of acute diarrhoea and rotavirus shedding in infants admitted to hospital.


Anomalies in the influenza virus genome database: new biology or laboratory errors?
A search of the influenza virus genome database reveals anomalies associated with a nonnegligible number of submitted sequences. There are many pairs of viral segments that are very close to each other in nucleotide sequence but relatively far apart in reported time of isolation, resulting in an abnormally low evolutionary rate. Also, some sequences show clear evidence of apparent homologous recombination, a process normally assumed to be extremely rare or nonexistent in this virus. These findings may point to surprising new biology but are perhaps more readily explained by stock contamination or other errors in the sequencing laboratories.


Gabapentin Inhibits Protein Kinase C Epsilon Translocation in Cultured Sensory Neurons with Additive Effects When Coapplied with Paracetamol (Acetaminophen).
Gabapentin is a well-established anticonvulsant drug which is also effective for the treatment of neuropathic pain. Although the exact mechanism leading to relief of allodynia and hyperalgesia caused by neuropathy is not known, the blocking effect of gabapentin on voltage-dependent calcium channels has been proposed to be involved. In order to further evaluate its analgesic mechanisms, we tested the efficacy of gabapentin on protein kinase C epsilon (PKCε) translocation in cultured peripheral neurons isolated from rat dorsal root ganglia (DRGs). We found that gabapentin significantly reduced PKCε translocation induced by the pronociceptive peptides bradykinin and prokineticin 2, involved in both inflammatory and chronic pain. We recently showed that paracetamol (acetaminophen), a very commonly used analgesic drug, also produces inhibition of PKCε. We tested the effect of the combined use of paracetamol and gabapentin, and we found that the inhibition of translocation adds up. Our study provides a novel mechanism of action for gabapentin in sensory neurons and suggests a mechanism of action for the combined use of paracetamol and gabapentin, which has recently been shown to be effective, with a cumulative behavior, in the control of postoperative pain in human patients.


Pannexin 2 protein expression is not restricted to the CNS.
Pannexins (Panx) are proteins homologous to the invertebrate gap junction proteins called innexins (Inx) and are traditionally described as transmembrane channels connecting the intracellular and extracellular compartments. Three distinct Panx paralogs (Panx1, Panx2 and Panx3) have been identified in vertebrates but previous reports on Panx expression and functionality focused primarily on Panx1 and Panx3 proteins. Several gene expression studies reported that Panx2 transcript is largely restricted to the central nervous system (CNS) hence suggesting that Panx2 might serve an important role in the CNS. However, the lack of suitable antibodies prevented the creation of a comprehensive map of Panx2 protein expression and Panx2 protein localization profile is currently mostly inferred from the distribution of its transcript. In this study, we characterized novel commercial monoclonal antibodies and surveyed Panx2 expression and distribution at the mRNA and protein level by real-time qPCR, Western blotting and immunofluorescence. Panx2 protein levels were readily detected in every tissue examined, even when transcriptional analysis predicted very low Panx2 protein expression. Furthermore, our results indicate that Panx2 transcriptional activity is a poor predictor of Panx2 protein abundance and does not correlate with Panx2 protein levels. Despite showing disproportionately high transcript levels, the CNS expressed less Panx2 protein than any other tissues analyzed. Additionally, we showed that Panx2 protein does not localize at the plasma membrane like other gap junction proteins but remains confined within cytoplasmic compartments. Overall, our results demonstrate that the endogenous expression of Panx2 protein is not restricted to the CNS and is more ubiquitous than initially predicted.


Assessment of urinary volatile compounds and proteins in the female goat Capra hircus: A pilot study to reveal potential indicators of oestrus.
Urine samples of female goats in pro-oestrus, oestrus and post-oestrus phases were analysed for finding oestrus-specific volatile compounds using gas chromatograph-mass spectrometry (GC-MS), and proteins using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). Fourteen urinary volatile were identified covering all three phases among which four compounds, 1-Tetradecanol, n-Pentadecanol, 3-Methylene tridecane and 2-Ethyl-1-dodecene, were unique to oestrus. Also, oestrus urine contained a 25 kDa protein, which was totally absent in pro-oestrus urine, and less-expressed in post-oestrus urine. This protein revealed to be complement C3 fragment. This pilot study, for the first time, reveals the difference in urinary volatile compounds and proteins in the female goat during the different phases of oestrous cycle. The four unique volatile compounds and a 25 kDa protein that appeared as oestrus-specific in this study warrant further investigation to consider them as urinary biomarkers of oestrus in goats.


Adipose tissue protects against sepsis-induced muscle weakness in mice: from lipolysis to ketones.
ICU-acquired weakness is a debilitating consequence of prolonged critical illness that is associated with poor outcome. Recently, premorbid obesity has been shown to protect against such illness-induced muscle wasting and weakness. Here, we hypothesized that this protection was due to increased lipid and ketone availability. In a centrally catheterized, fluid-resuscitated, antibiotic-treated mouse model of prolonged sepsis, we compared markers of lipolysis and fatty acid oxidation in lean and obese septic mice (n = 117). Next, we compared markers of muscle wasting and weakness in septic obese wild-type and adipose tissue-specific ATGL knockout (AAKO) mice (n = 73), in lean septic mice receiving either intravenous infusion of lipids or standard parenteral nutrition (PN) (n = 70), and in lean septic mice receiving standard PN supplemented with either the ketone body 3-hydroxybutyrate or isocaloric glucose (n = 49). Obese septic mice had more pronounced lipolysis (p ≤ 0.05), peripheral fatty acid oxidation (p ≤ 0.05), and ketogenesis (p ≤ 0.05) than lean mice. Blocking lipolysis in obese septic mice caused severely reduced muscle mass (32% loss vs. 15% in wild-type, p < 0.001) and specific maximal muscle force (59% loss vs. 0% in wild-type; p < 0.001). In contrast, intravenous infusion of lipids in lean septic mice maintained specific maximal muscle force up to healthy control levels (p = 0.6), whereas this was reduced with 28% in septic mice receiving standard PN (p = 0.006). Muscle mass was evenly reduced with 29% in both lean septic groups (p < 0.001). Lipid administration enhanced fatty acid oxidation (p ≤ 0.05) and ketogenesis (p < 0.001), but caused unfavorable liver steatosis (p = 0.01) and a deranged lipid profile (p ≤ 0.01). Supplementation of standard PN with 3-hydroxybutyrate also attenuated specific maximal muscle force up to healthy control levels (p = 0.1), but loss of muscle mass could not be prevented (25% loss in both septic groups; p < 0.001). Importantly, this intervention improved muscle regeneration markers (p ≤ 0.05) without the unfavorable side effects seen with lipid infusion. Obesity-induced muscle protection during sepsis is partly mediated by elevated mobilization and metabolism of endogenous fatty acids. Furthermore, increased availability of ketone bodies, either through ketogenesis or through parenteral infusion, appears to protect against sepsis-induced muscle weakness also in the lean.


Alcohol: the lubricant to suicidality.
Suicide is a major public health problem in the United States as well as around the world. The significant role that alcohol plays in suicidality is well known and accepted in the scientific community. The use of alcohol does not necessarily lead to suicide, but through its action and effects, alcohol is an important proximal risk factor for suicidal behavior. There is very little data showing how and why alcohol exerts such tremendous influence and "lubricates the gears" to propel the act of committing suicide. This article will elucidate the complex relationship between alcohol and suicide and how alcohol use can lead to suicide. The article also describes how alcohol affects brain neurophysiology in regards to suicidal behavior.


The impact of hospitalization on potentially inappropriate prescribing in an acute medical geriatric division.
Screening Tool of Older Person's Prescriptions (STOPP) and the Screening Tool to Alert doctors to Right Treatment (START) have been increasingly used to evaluate potentially inappropriate prescriptions (PIPs) and potentially prescription omissions (PPOs). The impact of hospitalization on PIPs/PPOs has not been investigated in depth. To compare the prevalence of PIPs/PPOs in elderly patients on hospital admission and discharge and to identify associated risk factors. An acute medical geriatric division of the Tel Aviv Medical Center (Israel). This retrospective cross-sectional study included patients admitted from 12/2011 to 12/2012 aged ≥65 years. Data from patients' records included demographic details, diagnoses and medications at admission and discharge. STOPP/START criteria were applied to each patient's record. Prevalence of PIPs/PPOs on hospital admission and discharge. Three hundred patients were included (mean ± SD age 81.9 ± 7.2 years). Admission PIPs prevalence was 39.3 % (118 patients, 172 PIPs) and it increased to 46.0 % (138 patients, 209 PIPs) at discharge (P = 0.009). Admission PPOs prevalence was 41.0 % (123 patients, 153 PPOs) and it decreased to 28.3 % (85 patients, 99 PPOs) at discharge (P < 0.001). Having at least one PIP/PPO at discharge but not at admission was associated with length of hospital stay (OR 1.02, 95 % CI 1.001-1.03). History of falls increased the risk of being a "new PIP patient" (OR 2.25, 95 % CI 1.03-4.9), whereas diabetes increased the risk of being a "new PPO patient" (OR 3.86, 95 % CI 1.2-12.5). Hospitalization in a geriatric division resulted in an increase in PIPs and a decrease in PPOs. Strategies to reduce PIPs need to be implemented, especially for patients with longer hospital stay and a history of falls.


Elevated body temperature independently contributes to increased length of stay in neurologic intensive care unit patients.
Elevated temperature results in worse outcome in experimental models of cerebral ischemia and brain trauma. In critically ill neurologic and neurosurgical patients, elevated body temperature is common and is associated with neurologic deterioration and poor outcome. We sought to determine whether, after controlling for age, severity of illness, and complications, elevated body temperature remained an important predictor of intensive care unit (ICU) and hospital length of stay, mortality rate, and hospital disposition in a large cohort of patients emergently admitted to a neurologic ICU. Prospectively collected data (demographics, diagnosis, Acute Physiology and Chronic Health Evaluation II score, Glasgow Coma Scale score, daily maximum temperature, complications, disposition) were retrospectively reviewed. A 20-bed neurology/neurosurgery ICU in a tertiary care academic, level I trauma, referral center. From 6,759 admissions, those admitted after an elective procedure with length of stay < or = 1 day, those <18 yrs old, and those with incomplete data were excluded, leaving 4,295 patients for this analysis. First, a hierarchical multiple regression analysis was performed to determine whether elevated body temperature was an independent predictor of length of stay. Second, a path analysis was performed to define the relationships among elevated body temperature, complications, and length of stay. Finally, a matched, weighted sample was developed to quantify the difference in length of stay. None. We measured ICU and hospital length of stay, mortality rate, and discharge disposition. The presence of elevated body temperature was associated with a dose-dependent longer ICU and hospital length of stay, higher mortality rate, and worse hospital disposition. The most important predictor of ICU length of stay was the number of complications (beta =.681) followed by elevated body temperature (beta =.143). In the matched, weighted population, the presence of elevated body temperature was associated with 3.2 additional ICU days and 4.3 additional hospital days. In a large cohort of neurologic ICU patients, after we controlled for severity of illness, diagnosis, age, and complications, elevated body temperature was independently associated with a longer ICU and hospital length of stay, higher mortality rate, and worse outcome.


Comparison of 3T and 7T ASL techniques for concurrent functional perfusion and BOLD studies.
Arterial spin labeling (ASL) is the primary non-invasive MRI approach to measure baseline cerebral blood flow (CBF) in healthy subjects and patients. ASL also allows concurrent functional BOLD signal and CBF measurements, but the latter typically suffer from low contrast-to-noise (CNR) ratio. Ultra-high-field imaging significantly boosts BOLD signal CNR. However, it is contested whether also CBF CNR benefits from increasing magnetic field strength, especially given that technical challenges related to field inhomogeneities and power deposition constraints exist. Recently, we presented an optimized PASL technique that utilizes tr-FOCI inversion pulses and dielectric pads to overcome the temporal resolution limitations of previous 7T ASL implementations (Ivanov et al., in press; 2017). The primary goal of this study was to compare its performance to that of 3T ASL approaches - both pulsed ASL (PASL) and pseudo-continuous (pCASL) - concerning functional studies using simultaneous CBF and BOLD signal acquisition. To this aim, we investigated a wide range of parameters that can influence CBF and BOLD signal sensitivities: spatial resolution, labeling scheme, parallel imaging and echo time. We found that 7T ASL is superior in terms of CBF and BOLD temporal signal-to-noise ratio (SNR) and activation volume compared to all 3T ASL variants, in particular at high spatial resolution. Our results show that the advantages of 7T for ASL stem from increased image SNR, especially when parallel imaging is used. The gray matter baseline CBF was in good agreement for all 3T ASL variants, but a significantly lower value was obtained at 7T. The labeling scheme utilized was also found to significantly influence the measured perfusion territories CBF. In conclusion, a single-echo accelerated 7T PASL is recommended for high spatial and temporal resolution CBF and BOLD imaging, while a 3T dual-echo pCASL approach without parallel imaging may be preferred for low (i.e., 3mm isotropic and lower) resolution functional perfusion and BOLD applications.


Detection of Iliopsoas Hematoma by Retrospective Radiography in Veno-Venous Extracorporeal Membrane Oxygenation for a COVID-19 Patient.
In coronavirus disease 2019 (COVID-19), veno-venous extracorporeal membrane oxygenation (VV-ECMO) is used to manage respiratory distress. This study's key clinical question was whether COVID-19 could be complicated by hemorrhagic and thrombotic events, such as iliopsoas hematoma (IPH), during the management of ECMO and the method to quickly and effectively detect IPH. A 52-year-old man with fever and dyspnea was diagnosed with COVID-19 pneumonia. He warranted VV-ECMO management on day 9, which was successfully tapered off on day 18. On day 20, computed tomography revealed a unilateral iliopsoas hematoma that was successfully managed with conservative care. However, a retrospective review of abdominal radiography performed on day 14 revealed a positive left psoas sign. When managing severe COVID-19 patients with VV-ECMO, cautious anticoagulative care and abdominal X-ray findings are warranted when considering the diagnosis of iliopsoas hematoma, including circulatory instability, anemia, and pain associated with limb movement.


Alcohol consumption and body weight change in postmenopausal women: results from the Women's Health Initiative.
To determine whether alcohol consumption is associated with incident overweight or obesity in normal-weight, postmenopausal women. Prospective cohort study considering baseline alcohol consumption and subsequent weight change over 7 years. 15,920 normal-weight (body mass index (BMI): 18.5 to <25 kg m(-2)), postmenopausal women enrolled in the Women's Health Initiative Clinical Trial. Body weight change, and incident overweight and obesity (BMI, 25.0 to <30 and ≥ 30 kg m(-2)) over 7 years. One-third of the 13,822 women included in the analytical cohort reported no alcohol consumption. BMI differed little between abstainers (22.8±1.58 kg m(-2)) and alcohol consumers in the upper quintile (22.7±1.53 kg m(-2)). Among normal-weight women, the risk of becoming overweight or obese over a 7-year follow-up period was 35% or 88% lower, respectively, for women in the upper quintile of alcohol intake relative to abstainers (hazard ratio (HR), 0.65; 95% confidence interval (CI), 0.58-0.73; or HR, 0.12; 95% CI, 0.05-0.25, respectively). Risk for overweight and obesity was not significantly modified by age. Wine consumption showed the greatest protective association for risk of overweight (HR, 0.75; 95% CI, 0.68-0.84), followed by liquor (HR, 0.85; 95% CI, 0.78-0.93) and beer (HR, 0.90; 95% CI, 0.82-1.00). Postmenopausal women of normal weight who report moderate alcohol intake have a reduced risk of becoming overweight or obese over time. Perhaps, weight control measures in this population should target behaviors other than reduction in alcohol for those of normal BMI consuming moderate amounts.


Linoleic Acid: A Nutritional Quandary.
Over the course of the twentieth century, there was a 20-fold increase in consumption of vegetable oils resulting both from their increased availability and from recommendations to consume these oils as an aid to lower blood cholesterol levels. This dietary change markedly increased the consumption of linoleic acid to current levels of approximately 6% of total dietary energy. While considerable research has focused on the effects of dietary linoleic acid on cardiovascular health, questions about optimum dietary levels remain. For example, meta-analyses disagree about the role of dietary linoleic acid in atherosclerosis, and recent publications indicate that linoleic acid's reduction of blood cholesterol levels does not predict its effect on the development of atherosclerosis. Further, there are also detrimental effects of elevated dietary linoleic acid on human health related to its role in inflammation and its activity as a promoter of cancer in animals. Current data do not allow determination of the level of dietary linoleic acid needed for optimum health. Studies of the effects of a wide range of linoleic acid consumption may help determine dietary recommendations that are optimal for human health.


The charnockite geotherm.
Charnockite, a hypersthene-bearing granite, and other associated rocks of the charnockite series have a global distribution. These rocks, according to evidence from mineral-chemical and experimental phase equilibrium relations, formed or recrystallized at temperatures between 800 degrees and 900 degrees C and at relatively shallow depths of 6 to 12 kilometers. This evidence indicates the existence of geothermal gradients of 70 degrees to 100 degrees C per kilometer probably at various times, the latest being around 1300 x 10(6) years ago.


Overfatness, stunting and physical inactivity are determinants of plasminogen activator inhibitor-1activity, fibrinogen and thrombin-antithrombin complex in African adolescents.
We examined fibrinogen, thrombin-antithrombin complex, factor VIIIc and plasminogen activator inhibitor-1 activity in African children in order to determine haemostatic profile patterning and to identify possible subdivisions at high risk for cardiovascular disease. In a cross-sectional analysis, a convenience sample of 117 girls and 78 boys (15.6 +/- 1.35 years) in a South African township was investigated within the Physical Activity in Youth study. Haemostatic variables were investigated in the total group and subdivisions for physical activity levels, maturity (Tanner staging), sex, fat percentage and height for age. Overfatness (53.6%) coexisted with stunting (17.5%). Plasminogen activator inhibitor-1 activity differed significantly between the sexes after adjustments for fat percentage and physical activity levels. Sex explained 10% and muscle mass 1% of the variance in plasminogen activator inhibitor-1 activity. Fibrinogen was significantly higher in girls than in boys (before adjustment for fat percentage), in overfat than in lean children and in stunted than in the nonstunted children (even after adjustment for fat percentage). C-reactive protein, sex and height for age were predictors of fibrinogen. Thrombin-antithrombin complex was significantly higher in girls than in boys, but after separate adjustment for physical activity and fat percentage there were no significant differences. Fitness and muscle mass explained the variance in thrombin-antithrombin complex the best. No significant differences were seen between the groups for C-reactive protein and factor VIIIc. Overfatness, stunting and inactivity negatively influenced plasminogen activator inhibitor-1 activity, fibrinogen and thrombin-antithrombin complex possibly increased the risk for cardiovascular disease. These factors are modifiable through behavioural changes and optimal nutritional status throughout the early life.


Exploiting conserved structure for faster annotation of non-coding RNAs without loss of accuracy.
Non-coding RNAs (ncRNAs)-functional RNA molecules not coding for proteins-are grouped into hundreds of families of homologs. To find new members of an ncRNA gene family in a large genome database, covariance models (CMs) are a useful statistical tool, as they use both sequence and RNA secondary structure information. Unfortunately, CM searches are slow. Previously, we introduced 'rigorous filters', which provably sacrifice none of CMs' accuracy, although often scanning much faster. A rigorous filter, using a profile hidden Markov model (HMM), is built based on the CM, and filters the genome database, eliminating sequences that provably could not be annotated as homologs. The CM is run only on the remainder. Some biologically important ncRNA families could not be scanned efficiently with this technique, largely due to the significance of conserved secondary structure relative to primary sequence in identifying these families. Current heuristic filters are also expected to perform poorly on such families. By augmenting profile HMMs with limited secondary structure information, we obtain rigorous filters that accelerate CM searches for virtually all known ncRNA families from the Rfam Database and tRNA models in tRNAscan-SE. These filters scan an 8 gigabase database in weeks instead of years, and uncover homologs missed by heuristic techniques to speed CM searches. Software in development; contact the authors.


Reproducibility of proximal probe pH parameters in 24-hour ambulatory esophageal pH monitoring.
To assess the reproducibility and reliability of the proximal pH probe in detecting acid reflux into the proximal esophagus. Using dual probe ambulatory esophageal pH monitoring, we studied 32 subjects (11 healthy control subjects, 10 patients with distal esophageal acid reflux, and 11 patients with both distal and proximal esophageal acid exposure) on two separate days within a 20-day period. The distal pH probe was placed 5 cm above the manometrically determined lower esophageal sphincter, and the proximal probe was positioned immediately distal to the upper esophageal sphincter. Patients were categorized on the basis of the esophageal pH data obtained during the first study. Reflux parameters assessed were the percentages of time in which pH was <4 in the total, upright, and supine positions. To be considered reproducible, all three of the above parameters had to remain in the same category as the first day's results. Intrasubject reproducibility of the proximal probe was 91-100% in healthy subjects, 70-90% in patients with distal esophageal acid reflux, and 45-73% in patients with proximal esophageal acid reflux. The proximal probe reproducibility for the overall diagnosis of gastroesophageal reflux disease was 91% in healthy subjects, 70% in patients with distal esophageal acid reflux, and only 55% in those with proximal esophageal acid reflux. Statistical analysis demonstrated only a fair index of concordance (kappa = 0.40) for the proximal probe. The proximal pH probe has excellent specificity (91%) but poorer sensitivity and reproducibility (55%) for identifying abnormal amounts of proximal esophageal acid reflux. Therefore, a negative test result does not exclude proximal reflux with microaspiration as a cause of atypical reflux symptoms.


Transesophageal Echocardiographic Diagnosis and Management of Circumflex Artery Injury Following Mitral Valve Repair.
A 16-year-old woman with severe mitral regurgitation as a result of rheumatic heart disease underwent mitral valve repair with posterior mitral annuloplasty. ST elevation was observed in leads II, III and aVF after weaning from cardiopulmonary bypass. On transesophageal echocardiography, the stenosis of the circumflex artery was suggested by a modified midesophageal long axis. Since the patient was hemodynamically unstable, an emergency coronary angiography could not be considered. An urgent cardiopulmonary bypass was re-instituted; the first two sutures in the P1 region of the posterior mitral annulus were translocated more superficially. Transesophageal echocardiography revealed good opening of the circumflex artery and improvement in regional wall motion abnormality following the corrected procedure.


Silica Exposure and Effect on Peak Expiratory Flow: Slate Pencil Workers' Study.
Peak expiratory flow (PEF) is a spirometric test that detects obstructive changes in the respiratory tract; has good correlation with the FEV1; and is much less expensive, simpler, and easier to perform under field conditions than FEV1. Chronic silicosis is also known to have obstructive features in advanced stages. Thus, this study was performed to assess the effect of silica exposure on PEF and the factors related to it. The present study was carried out among 193 slate pencil cutting workers of Multanpura village of Madhya Pradesh, India. An interview technique was used to record demographic characteristics and occupational history on a predesigned form, which included a questionnaire regarding occupational history and silica-related respiratory morbidities. This was followed by a complete medical examination and measurement of PEF using a spirometer. The mean age was 43.35 ± 11.31 y, and the mean duration of exposure was 18.72 ± 9.33 y. In the present study, PEF was found to be significantly reduced in those age ≥40 y, those who were female, those having duration of exposure >10 y, and those having respiratory morbidity, whereas the reduction in PEF was statistically nonsignificant for smokers. Higher age, female sex, higher duration of exposure, and respiratory morbidity were found to be important correlates of PEF.


Crystal structures of two cyanobacterial response regulators in apo- and phosphorylated form reveal a novel dimerization motif of phytochrome-associated response regulators.
The structures of two response regulators (RRs) from the cyanobacterium Calothrix PCC7601, RcpA and RcpB, were solved to 1.9- and 1.75-A resolution, respectively. RcpA was found in phosphorylated and RcpB in nonphosphorylated form. Both RRs are members of phytochrome-associated, light-sensing two-component signal transduction pathways, based on histidine kinase-mediated receptor autophosphorylation and phosphorelay to a RR. Despite the overall folding similarity to CheY-type RRs ((beta/alpha)(5)-motif), RcpA and RcpB form homodimers, irrespective of their phosphorylation state, giving insight into a signal transduction putatively different from that of other known RRs. Dimerization is accomplished by a C-terminal extension of the RR polypeptide chain, and the surface formed by H4, beta 5, and H5, which constitute a hydrophobic contact area with distinct interactions between residues of either subunit. Sequence alignments reveal that the identified dimerization motif is archetypal for phytochrome-associated RRs, making them a novel subgroup of CheY-type RRs. The protein structures of RcpA and RcpB are compared to the recently presented protein structure of Rcp1 from Synechocystis.


Cryopreservation-induced nonattachment of human hepatocytes: role of adhesion molecules.
Good quality cryopreserved human hepatocytes are becoming an important source for clinical hepatocyte transplantation. However, the process of cryopreservation leads to both structural and functional impairment of hepatocytes. The aim of this study was to investigate the mechanisms of cryopreservation-induced nonattachment in human hepatocytes. Hepatocytes were cryopreserved after isolation from unused donor liver tissue. Cell attachment to collagen-coated plates was measured. A cDNA gene array system for 96 cell adhesion-related molecules was used to determine mRNA expression in fresh and cryopreserved hepatocytes. Two cell adhesion molecule proteins were investigated further: beta1-integrin, a cell-matrix adhesion molecule, and E-cadherin, a cell-cell adhesion molecule. Attachment efficiency was significantly decreased after cryopreservation of human hepatocytes. Twenty-two genes were downregulated after cryopreservation including integrins, cadherins, catenins, and matrix metalloproteinases (MMPs). Beta1-Integrin gene and protein expression were significantly decreased in cultured cryopreserved hepatocytes compared to fresh hepatocytes. There was a significant correlation between loss of beta1-integrin and attachment in cryopreserved cells. Degradation of E-cadherin was increased in cryopreserved hepatocytes. The process of cryopreservation leads to downregulation of cell adhesion molecules at the gene and the cellular level. New cryopreservation protocols are needed to prevent these effects on cell attachment.


Endoluminal resection of gastric intestinal stromal tumors (GIST).
Endoluminal surgery, the combination of flexible endoscopy and percutaneous transgastric laparoscopy, has expanded the role of minimally invasive surgery in treating foregut diseases. This imaginative technique blends the skills of endoscopist and laparoscopist. The stomach is well-suited for this technique as it is an expandable, large volume organ readily accessible to a flexible endoscope, and the relative ease of placing endoscopically or laparoscopically-guided percutaneous, transgastric ports provides access for laparoscopic instrumentation. The resection of gastric stromal tumors provides one of the few opportunities to integrate flexible endoscopy and laparoscopy. Proper training in the appropriate indications to utilize endoluminal techniques and familiarity with the multiple modifications from the original intragastric techniques described nearly a decade ago will allow surgeons to approach small, predominately endoluminal gastric stromal tumors with low malignant potential located in the cardia, along the posterior gastric wall, near the gastroesophageal junction or proximal to the pylorus.


Dental implant replacement of the mandibular first molar tooth in a dog.
A new dental implant system was used to replace the mandibular right first molar tooth in an eleven-month-old male/intact, utility trained German shepherd dog. The permanent mandibular right first molar tooth had been extracted as treatment for an extensive carious lesion when the dog was 9-months of age. There were no complications associated with placement of the dental implant. However, peri-implant osteomyelitis occurred secondary to a traumatic oral wound 6-months following implant placement. The 17-month post-operative examination indicated that the implant system used in this case could be maintained in a working dog that uses extreme bite forces. However, periodontal inflammation and vertical bone loss exposing the implant fixtures were noted during oral examination. Further clinical applications are required to determine if the periodontal inflammation and vertical bone loss noted in this case were complications associated with the implant, maturity of bone at the time of implant fixture placement, general biting/chewing forces placed on carnassial teeth, or the oral trauma that occurred 6-months following implant placement.


Sertraline in social phobia.
Eleven consecutive SCID-diagnosed generalized social phobias without major depression, other prominent anxiety disorders, substance abuse, alcoholism or organic mental disorder, were treated, open label, with sertraline up to 200 mg daily for 12 weeks. There were seven completers. Of these, five showed substantial improvement, after being on sertraline 100 mg daily for two weeks (following no response to sertraline 50 mg daily for four weeks). There were few side effects among the completers. The four dropouts complained of side effects and loss of interest in continuing treatment. Final average dose for completers who responded was 170 mg daily.