Dual acting and pan-PPAR activators as potential anti-diabetic therapies.
The thiazolidinedione PPAR-γ activator drugs rosiglitazone and pioglitazone suppress insulin resistance in type 2 diabetic patients. They lock lipids into adipose tissue triglyceride stores, thereby preventing lipid metabolites from causing insulin resistance in liver and skeletal muscle and β-cell failure. They also reduce the secretion of inflammatory cytokines such as TNFα and increase the plasma level of adiponectin, which increases insulin sensitivity in liver and skeletal muscle. However, they have only a modest effect on dyslipidaemia, and they increase fat mass and plasma volume. Fibrate PPAR-α activator drugs decrease plasma triglycerides and increase HDL-cholesterol levels. PPAR-δ activators increase the capacity for fat oxidation in skeletal muscle.Clinical experience with bezafibrate, which activates PPAR-δ and -α, and studies on the PPAR-α/δ activator tetradecylthioacetic acid, the PPAR-δ activator GW501516, and combinations of the PPAR-α activator fenofibrate with rosiglitazone or pioglitazone have encouraged attempts to develop single molecules that activate two or all three PPARs. Most effort has focussed on dual PPAR-α/γ activators. These reduce both hyperglycaemia and dyslipidaemia, but their development has been terminated by issues such as increased weight gain, oedema, plasma creatinine and myocardial infarction or stroke. In addition, the FDA has stated that many PPAR ligands submitted to it have caused increased numbers of tumours in carcinogenicity studies.Rather than aiming for full potent agonists, it may be best to identify subtype-selective partial agonists or compounds that selectively activate PPAR signalling pathways and use these in combination. Nutrients or modified lipids that are low-affinity agonists may also have potential.


Quantifying climate variation and associated regional air pollution in southern India using Google Earth Engine.
Climate change and regional air pollution have had significant proportional coherence and are collectively hazardous for the regional ecosystem. To conduct this present investigation, we obtained high-resolution remotely sensed datasets from 2001 to 2022. To estimate climate variation, we utilized Climate Hazard Group InfraRed Precipitation with Station Data Version 2.0 (CHIRPS) and Moderate Imaging Spectroradiometer (MODIS) Land Surface Temperature (LST). Additionally, we used Sentinel-5P datasets to collect spatio-temporal information for regional CO (Carbon Monoxide), NO2 (Nitrogen Dioxide), SO2 (Sulfur Dioxide), and UV Aerosol index for Coimbatore city. Numerous non-parametric and descriptive statistical applications were then employed to check the spatial integrity of satellite data products and spatio-temporal trends using Google Earth Engine algorithms. The study reveals most of the southern parts of Coimbatore city witnessed increased LST (0.10 °C/year) together with decreased rainfall (21.5 mm/year). Moreover, regional concentration of air pollutants exhibits spatio-temporal variability at annual and seasonal scales, where maximum engrossment is occupied by CO during the pre-monsoon and monsoon season. However, other pollutants are also dominant in the northern parts of the city, whereas NO2 and absorbing Aerosol during pre-monsoon season experienced significant increase throughout the years. Understanding the fluctuations in air pollution levels across different weather situations might help in developing targeted pollution reduction methods.


[Topical therapy of the scalp].
Various hair-related diseases, systemic dermatoses as well as parasitic diseases are treated via topical application of active substances. The density of hair follicles and the consequential special conditions for diffusion require specific galenic concepts that can vary considerably depending on the respective therapeutic purpose. Both the physicochemical properties of the active ingredient and the nature of the application area must be considered when choosing an appropriate galenic base. Highly relevant here are hairiness, scarring, hyperkeratosis and exoserosis. Low-viscosity bases and foams are often preferred because of their good spreadability. Packages with nozzle tip or comb-shaped dispensers are user-friendly and can significantly enhance patient adherence to topical treatment.


The Optimal Ileal Pouch: Physiologic Parameters Significantly Correlate with Overall Pouch Function.
Ileal pouch function is affected by several patient factors and pouch physiology. The significance of pouch physiology on optimal pouch function has not been well characterized. The purpose of this study was to examine specific post-ileal pouch anal anastomosis (IPAA) physiologic parameters to determine impact on pouch function and quality of life. Patients undergoing proctocolectomy with IPAA for ulcerative colitis were examined. Post-IPAA compliance, pouch anal pressure gradient (PAPG), and function were assessed 6-8 months postoperatively. Compliance was calculated as change in volume divided by change in pressure. PAPG was calculated as the difference between anal pressure and intra-pouch pressure at a fixed volume. Pouch function evaluation included stool frequency and episodes of incontinence. Quality of life was evaluated using the Rockwood Fecal Incontinence Quality of Life Scale. A total of 125 patients were investigated. Post-IPAA resting anal pressure averaged 58.1 ± 15 mmHg. Mean volume and intra-pouch pressure at evacuation were 245 mL and 33.9 mmHg, respectively. Compliance averaged 11.2 mmHg/mL with a mean PAPG of - 29.3 mmHg. Compliance and PAPG correlated with 24-h (p = 0.003, p = 0.004) and nighttime stool frequency (p = 0.04, p = 0.03). Daytime continence was impacted by compliance (p = 0.04), PAPG (p = 0.02), and resting anal pressure (p = 0.02). This unique evaluation reveals a significant correlation between IPAA physiologic properties and function. Optimal function and quality of life depend in part on maintaining optimal pouch compliance and pressure differentials between the pouch and anal canal, defined by the pouch anal pressure gradient.


1,25-dihydroxyvitamin D3 impairs NF-κB activation in human naïve B cells.
1α,25-dihydroxyvitamin D(3) (calcitriol), the bioactive metabolite of vitamin D, modulates the activation and inhibits IgE production of anti-CD40 and IL-4 stimulated human peripheral B cells. Engagement of CD40 results in NF-κB p50 activation, which is essential for the class switch to IgE. Herein, we investigated by which mechanism calcitriol modulates NF-κB mediated activation of human naïve B cells. Naïve B cells were predominantly targeted by calcitriol in comparison with memory B cells as shown by pronounced induction of the VDR target gene cyp24a1. Vitamin D receptor activation resulted in a strongly reduced p105/p50 protein and mRNA expression in human naïve B cells. This effect is mediated by impaired nuclear translocation of p65 and consequently reduced binding of p65 to its binding site in the p105 promoter. Our data indicate that the vitamin D receptor reduces NF-κB activation by interference with NF-κB p65 and p105. Thus, the vitamin D receptor inhibits costimulatory signal transduction in naïve B cells, namely by reducing CD40 signaling.


Calcium involvement in luteinizing hormone-releasing hormone release from the bovine infundibulum.
Bovine infundibular (stalk median eminence) explants were incubated in vitro to test the hypothesis that calcium (Ca) is involved in the release of luteinizing hormone-releasing hormone (LHRH) from LHRH neuron terminals in cattle. Right and left infundibular halves from individual heifers and/or steers were randomly assigned to either control or treated (EGTA [a Ca chelator] or verapamil [an L-type Ca channel antagonist]) groups. Each half was incubated in 600 microliters of Krebs-Ringer bicarbonate medium (KRB) in the presence or absence of a treatment agent for 180 min. At 30-min intervals, 500-microliters samples were removed from each incubated and replaced with fresh media. Spontaneous (basal) and depolarization-induced (60 mM potassium) LHRH release was evaluated by radioimmunoassay of the LHRH content in the media incubated from 91 to 120 and 121 to 150 min of culture, respectively. The effect of treatment on depolarization-induced LHRH release was analyzed by comparing the differences between spontaneous and depolarization-induced LHRH release in control and treated groups. Spontaneous LHRH release was not different between control and 1.25 mM EGTA- or 100 microM verapamil-treated halves from steers. In contrast, steer infundibular halves incubated with EGTA (replacing Ca in KRB and chelating any Ca in the media) released less LHRH during depolarization than did control halves. In addition, verapamil-treated (to block Ca uptake by the terminal) infundibular halves from steers or heifers released less LHRH in response to depolarization than did control halves.(ABSTRACT TRUNCATED AT 250 WORDS)


Stabilization of systems with interval time-varying delay based on delay decomposing approach.
The paper considers the stabilization for systems with interval time-varying delay. By decomposing the delay interval into multiple equidistant subintervals and considering the triple integral terms, a novel Lyapunov-krasovskii functional(LKF) is defined. Then extended integral inequality and convex combination approach are used to estimate the derivative of the constructed functional, and as a result, the new stability criterion with less conservatism and decision variables is obtained. On this basis, the state feedback controller is designed, by using linearization method, the existence condition of controller is obtained in terms of linear matrix inequalities(LMIs), and the specific form of controller is also given, moreover, by selecting the appropriate parameter value, the stabilization time of the system can be reduced. Numerical examples are given to illustrate the effectiveness of the proposed method.


Role of Bibersteinia trehalosi, respiratory syncytial virus, and parainfluenza-3 virus in bighorn sheep pneumonia.
Pneumonic bighorn sheep (BHS) have been found to be culture- and/or sero-positive for Bibersteinia trehalosi, respiratory syncytial virus (RSV), and parainfluenza-3 virus (PI-3). The objective of this study was to determine whether these pathogens can cause fatal pneumonia in BHS. In the first study, two groups of four BHS each were intra-tracheally administered with leukotoxin-positive (Group I) or leukotoxin-negative (Group II) B. trehalosi. All four animals in Group I developed severe pneumonia, and two of them died within 3 days. The other two animals showed severe pneumonic lesions on euthanasia and necropsy. Animals in Group II neither died nor showed gross pneumonic lesions on necropsy, suggesting that leukotoxin-positive, but not leukotoxin-negative, B. trehalosi can cause fatal pneumonia in BHS. In the second study, two other groups of four BHS (Groups III and IV) were intra-nasally administered with a mixture of RSV and PI-3. Four days later, RSV/PI-3-inoculated Group IV and another group of four BHS (Group V, positive control) were intra-nasally administered with Mannheimia haemolytica, the pathogen that consistently causes fatal pneumonia in BHS. All four animals in group III developed pneumonia, but did not die during the study period. However all four animals in Group IV, and three animals in Group V developed severe pneumonia and died within two days of M. haemolytica inoculation. The fourth animal in Group V showed severe pneumonic lesions on euthanasia and necropsy. These findings suggest that RSV/PI-3 can cause non-fatal pneumonia, but are not necessary predisposing agents for M. haemolytica-caused pneumonia of BHS.


In-silico study of seaweed secondary metabolites as AXL kinase inhibitors.
AXL kinase is an attractive cancer target for drug design and it is involved in different cancers. A set of molecule databases with 1072 secondary metabolites from seaweeds were screened against the AXL kinase active site and eight molecules were shortlisted for further studies. From the docking analysis of the complexes, four molecules GA011, BE005, BC010, and BC005 are showing prominent binging. From the 100 ns of molecular dynamics simulations and ligand-bound complex MM-PBSA free energy analysis, two molecules BC010 (ΔG = -135.38 kJ/mol) and BE005 (ΔG = -141.72 kJ/mol) are showing molecule stability in the active site also showing very strong binding free energies. It suggests these molecules could be the potent molecules for AXL kinase.


Clinical and pathological studies in cattle with hepatic disease.
In cattle with hepatic lipidosis, hepatic abscessation, leptospirosis, biliary calculi or fasciolosis, the progression of the disease was studied by serial measurements of serum total bile acid concentrations, plasma glutamate dehydrogenase, gamma-glutamyltransferase, 5'-nucleotidase and leucine aminopeptidase activities Terminalia avicennioides and by liver biopsy. Regardless of the cause of the hepatic disease, weight loss, anorexia, dullness and depression were consistent features. Signs of hepatic encephalopathy, such as blindness, head pressing, excitability, ataxia and weakness were less common and, together with pyrexia and jaundice, were grave prognostic signs. Plasma ammonia concentrations were significantly elevated compared to clinically normal cattle, but such changes were not always accompanied by a decline in plasma urea concentrations. In normal, healthy cattle, the plasma ammonia:urea concentration ratio is 9:1 and the plasma ammonia:glucose concentration is 11:1. In hepatic disease, a plasma ammonia:glucose ratio > 40:1 or plasma ammonia:urea ratio > 30:1, particularly with a rising total ketone body concentration and a declining glucose concentration, carried a guarded prognosis. The study suggested that other factors, such as hypokalaemia, alkalosis, short-chain volatile fatty acids, and false and true neuro-transmitters, may be important in the pathogenesis of hepatic coma in cattle.


Left alien hand sign and mirror writing after left anterior cerebral artery infarction.
A 43-year-old, right-handed man was admitted complaining of peculiar movements of his left hand. Computed tomography scan and magnetic resonance imaging showed an infarct area in the territory of the left anterior cerebral artery. The abnormal movements of the left hand were diagnosed as so-called alien hand sign. This patient also exhibited mirror writing with his left hand. The clinical manifestations and neuroradiological findings of this case are described in detail, and the possible mechanisms of these extremely rare combinations of alien hand sign and mirror writing are discussed.


Treatment of Classic Hairy Cell Leukemia: Targeting Minimal Residual Disease beyond Cladribine.
Classic hairy cell leukemia (HCL) is a rare indolent B-cell lymphoproliferative disorder characterized by profound pancytopenia and frequent infectious complications due to progressive infiltration of the bone marrow and spleen. Lacking effective treatment options, affected patients were confronted with a dismal survival prognosis of less than 5 years when the disease was first described in 1958. Tremendous therapeutic advances were accomplished with the introduction of purine analogues such as cladribine in the 1990s, facilitating a near-normal life expectancy in most HCL patients. Nevertheless, nearly all patients eventually relapse and require successive retreatments, while drug-associated myelotoxicity may accumulate and secondary malignancies may evolve. Detection of minimal residual disease (MRD) in a substantial portion of treated patients has become a surrogate for this still limited treatment efficacy. In the last decade, novel biologic insights such as identification of the driver mutation BRAF V600E have initiated the development and clinical investigation of new, chemotherapy-free, targeted drugs in HCL treatment, with encouraging efficacy in early clinical trials aimed at boosting eradication of MRD while optimizing drug tolerability. This review summarizes current clinical trials investigating treatment strategies beyond purine analogues in HCL and discusses clinically relevant obstacles still to overcome.


Engagement in HIV Prevention Advocacy Associated with Increased Consistent Condom Use Among HIV Clients in Uganda.
We examined whether engagement in prevention advocacy among HIV clients is associated with their own condom use and HIV care adherence. Longitudinal data merged from three studies in Uganda produced a sample of 1,882 participants who were administered assessments at baseline and months 6 and 12. The measure of prevention advocacy was the mean of two Likert scale items assessing encouragement of others to (1) use condoms, and (2) get HIV tested. In regression analyses controlling for demographics and known correlates of the dependent variables, increased prevention advocacy from baseline to month 12 was significantly associated with increased consistent condom use and marginally associated with increased antiretroviral adherence and clinic attendance. These results suggest that empowering HIV clients to engage in prevention advocacy with others may benefit their own HIV protective behaviors and should be promoted as a component to interventions targeting positive living among people living with HIV.


Hemoglobin is inversely related to flow-mediated dilatation in chronic kidney disease.
The microcirculation is regulated by oxygen gradients and by endothelial release of nitric oxide, which can react with hemoglobin to form S-nitroso derivatives. Here we induced flow-mediated dilatation of the brachial artery in response to ischemia in 141 non-diabetic patients with stage 3-4 chronic kidney disease who had no history of smoking, cardiovascular events or use of erythropoietin-based agents. Patients with hemoglobin concentrations above the cohort median of 11.6 g/dl were found to have significant reductions in flow-mediated dilatation compared to those below the median. This inverse relationship remained significant after adjustment for potential confounders, including insulin sensitivity, glomerular filtration rate, proteinuria, body mass index, serum urate, etiology of underlying renal disease, treatment with anti-hypertensive drugs, and traditional Framingham risk factors. Given that hemoglobin can act as an important nitric oxide carrier and buffer, our studies suggest that the mechanism by which hemoglobin influences the endothelium-dependent microcirculation requires its nitrosylation; however, more direct studies need to be performed.


Defining clinical pharmacy and support activities indicators for hospital practice using a combined nominal and focus group technique.
Background Although clinical pharmacy is a crucial part of hospital pharmacist's day-to-day activity, its performance is not usually subject to a holistic assessment. Objective To define a set of relevant and measurable clinical pharmacy and support activities key performance indicators (cpKPI and saKPI, respectively). Setting Portuguese Hospital Pharmacies. Method After a comprehensive literature review focusing on the metrics already in use in other countries, several meetings with directors of hospital pharmacies were conducted to obtain their perspectives on hospital pharmacy practices and existing metrics. Finally, five rounds with a panel of 8 experts were performed to define the final set of KPIs, where experts were asked to score each indicator' relevance and measurability, and encouraged to suggest new metrics. Main outcome measure The first Portuguese list of KPIs to assess pharmacists' clinical and support activities performance and quality in hospital pharmacies. Results A total of 136 KPIs were assessed during this study, of which 57 were included in the original list and 79 were later added by the expert panel. By the end of the study, a total of 85 indicators were included in the final list, of which 40 are considered to be saKPI, 39 cpKPI and 6 neither. Conclusion A set of measurable KPIs was established to allow for benchmarking within and between Portuguese hospital Pharmacies and to elevate professional accountability and transparency. Future perspectives include the use of both cpKPIs and saKPIs on a national scale to identify the most efficient performances and areas of possible improvement.


Mathematical description and computer simulation of retinal cometlike afterimages: a modified neural equation with stability analysis.
A mathematical model for the spatiotemporal description of a well-known psychophysical phenomenon, the cometlike afterimage effect (CLAIE), is presented. The CLAIE occurs when a bright circular light spot moves slowly in the peripheral human retina. Under these conditions, the leading edge of the dot looks circular, but the trailing edge becomes elongated like a comet's tail whose length increases with speed and luminance, and the illusion is more prominent for photopic backgrounds. This cometlike motion smear is described on the basis of the temporal responsiveness and adaptation of rods. The model is an extension of an existing neural model of M. N. Oğuztöreli et al., with an additional term that allows prolonged saturation and long decay time following exposure to intense stimuli, and these effects are held responsible for the cometlike smear. The model predicts the response of photoreceptors through a nonlinear ordinary integrodifferential equation, which includes known biophysical terms for response dynamics, adaptation, saturation, and kinetics of intermediate components of the phototransduction process. The introduction of a saturation coefficient into the neural equation makes it possible to distinguish the different saturation thresholds of the rod-and-cone system. Numerical determination of the stationary solutions and complete linear stability analysis of the improved neural equation are given for a neuron of second order, and some computational results are presented for phase flows around different singular points in the phase field. A computer simulation based on the improved neural equation is presented for modeling the development and features of the CLAIE as a function of the speed and luminance of the stimulus and the background intensity. The computational results agree well with the psychophysical findings relating to the CLAIE.


Corrigendum: Contaminants from a former Croatian coal sludge dictate the structure of microbiota in the estuarine (Raša Bay) sediment and soil.
[This corrects the article DOI: 10.3389/fmicb.2023.1126612.].


On orthogonal and selective activation of glycosyl thioimidates and thioglycosides: application to oligosaccharide assembly.
Discrimination among S-thiazolinyl (STaz), S-benzoxazolyl (SBox), and S-ethyl anomeric leaving groups was achieved by fine-tuning activation conditions. Preferential glycosidation of a certain leaving group is determined neither by the strength of the activating reagent nor by the stability of the leaving group itself; instead, the type of activation plays the key role. The activation conditions established herein were applied to a sequential five-step synthesis of a hexasaccharide using six monosaccharide building blocks equipped with six different leaving groups.


The first single-incision plus one-port transverse colon resection using Senhance Digital Laparoscopy System: a case report.
We have introduced the Senhance Digital Laparoscopy System and actively use for colorectal cancer surgery. Recently, we also try to perform surgery by reduce port as less invasive method. For the first time, we report a case of single-incision plus one-port transverse colectomy using Senhance system. The case was a 57-year-old woman, diagnosed with transverse colon cancer referred to our department. The preoperative diagnosis was cT1bN0M0, Stage I. We performed single-incision plus one-port transverse colon resection using Senhance system without any problems. The operative time was 203 min and the blood loss was 35 ml. We report the first case of single-incision plus one-port transverse colectomy using Senhance system. We trust this approach will find increasing use, enabling a safer means of minimally invasive robotic surgery.


Expression and localization of the iron-siderophore binding protein lipocalin 2 in the normal rat brain and after kainate-induced excitotoxicity.
Lipocalin 2 (LCN2) is produced by mammalian hosts to bind bacterial siderophore and sequester free iron as part of an innate immune response, and could also play a role in tissue iron homeostasis, but thus far, little is known about its expression in the CNS. The present study was carried out to study the expression of the lipocalin in the normal rat brain and after neuronal injury induced by kainate (KA). Low levels of LCN2 mRNA and protein expression were detected in most regions of the normal brain except the olfactory bulb, brainstem and cerebellum. KA lesions resulted in damage to the hippocampus, leading to an early increase at three days and a sustained elevation in LCN2 mRNA level of 16-fold, and protein expression at 80-fold in the lesioned tissue compared to controls at 2 weeks post-KA injection. The sustained elevation in mRNA expression was not detected among other lipocalins surveyed using real-time RT-PCR - apoD, PGDS, Rbp4 and LCN5. Single and double immunostaining confirmed that LCN2 is present in astrocytes in the olfactory bulb, brainstem and cerebellum of the normal brain, and reactive astrocytes in the KA-lesioned hippocampus. In conclusion, the present study showed LCN2 to be present in select brain regions, and is upregulated in astrocytes after neuronal injury induced by kainate. We postulate that, as in the periphery, LCN2 may have a role in iron transport or trafficking in the CNS.


A focus on culture and leadership.
Sam Foster, Chief Nurse, Oxford University Hospitals, discusses 'compassionate leadership', an approach that aims to allow staff to provide the best care for patients by listening to and acting on staff concerns.


Measurement of immunoglobulin concentration in cell culture supernates by computer-assisted ELISA.
The enzyme-linked immunosorbent assay (ELISA) is used extensively in immunologic research for obtaining quantitative estimates of immunoglobulin concentration in cell culture supernates. Through incorporation of a microcomputer for data acquisition, storage and rapid calculation of results, a substantial reduction in total assay time may be realized. Described here are a set of menu-driven programs written in Basic for the IBM-PC which provide advantages over existing software in simplicity, versatility and accuracy. Hardware requirements are minimal. These programs should encourage greater flexibility in terms of the size and complexity of experimental designs.


Novel application of Angiojet rheolytic thrombectomy for massive thrombosis of the native aortic valve and Jarvick 2000 ventricular assist device in a patient with end-stage heart failure.
With the diffusion of implantable ventricular assist pumps in heart failure patients refractory to treatments or ineligible to transplantation, acute aortic valve and device thrombosis is an unusual but potentially increasing complication. We report a novel application of Angiojet rheolytic thrombectomy for acute and massive thrombosis of the native aortic valve and of the left ventricular assist device in a heart failure patient. The technical execution and clinical experience with this technique is described.


The induction by testosterone of aromatase activity in the preoptic area and activation of copulatory behavior.
A series of 4 experiments was designed to study the relationships between the activity of the aromatase (AA) in the preoptic area (POA) and the activation by testosterone (T) of copulatory behavior in gonadectomized male and female Japanese quail. The induction of AA by T in the POA is dose- and time-dependent. Levels of AA seen in sexually mature males are restored in castrated birds by a treatment with 20 to 40 mm silastic T capsules which produce physiological levels of steroid in the plasma. The minimal dose of T (10 mm implant) which reliably restores copulatory behavior approximately doubles the AA in the POA. The induction of AA is significantly larger in males than in females. A significant increase in AA is observed within 16 hours after the start of the treatment with T and the induction is maximal after 48 hours. Activation of copulatory behavior follows a similar time course but occurs with a delay of 24-48 hours. These results thus suggest that, in male quail, the activity of the aromatase in the POA is a limiting factor in the activation of copulatory behavior. This idea is confirmed by direct experimentation using an aromatase inhibitor, androstatrienedione (ATD). If T-treated birds receive at the same time silastic implants filled with ATD, the activation of behavior is suppressed for at least one week. This behavioral inhibition is, as expected, accompanied and very probably caused by the inhibition of the aromatase activity in the preoptic area and anterior hypothalamus. No increase of enzyme activity over the level seen in castrates was actually detected during the first 8 days of exposure to T. A moderate increase in AA was seen on day 16 and is probably responsible for the behavioral activation which was observed at the end of the experiment.


Immunoradiometric assay for intact human parathyroid hormone: characteristics, clinical application and comparison with a radio-immunoassay.
Circulating immunoreactive intact human parathyroid hormone (PTH) was measured by a direct immunoradiometric assay (IRMA) and the results compared with a radio-immunoassay (RIA) which required extraction and concentration prior to assay. The sensitivity of the IRMA was better than that of the RIA (0.6 vs 2.0 pmol/L). In control subjects the hPTH concentrations ranged between 0.6 and 6.7 pmol/L and in patients with hypercalcaemia due to malignant diseases, sarcoidosis and hypoparathyroidism none could be detected. In patients with primary hyperparathyroidism the concentrations ranged from 5.2 to 27.0 pmol/L. In patients with renal osteodystrophy serum human PTH concentrations ranged from 7.6 to 285 and in those with chronic renal failure but without evidence of renal osteodystrophy from 0.5 to 5.2 pmol/L. The major advantages of the IRMA are its much simpler performance and its higher sensitivity which makes studies of the physiology of PTH secretion in humans possible.


Lizhong Decoction Ameliorates Ulcerative Colitis in Mice via Regulation of Plasma and Urine Metabolic Profiling.
To elucidate the mechanism of Lizhong Decoction (LZD) in treating dextran sodium sulfate (DSS)-induced colitis in mice based on metabonomics. Thirty-six mice were randomly divided into 6 groups, including normal, model, low- (1.365 g/kg), medium- (4.095 g/kg) and high dose (12.285 g/kg) LZD and salazosulfadimidine (SASP) groups, 6 mice in each group. Colitis model mice were induced by DSS admistration for 7 days, and treated with low, medium and high dose LZD extract and positive drug SASP. Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) combined with Metabolynx™ software. The metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment (P<0.05). Potential biomarkers (9 in serum and 4 in urine) were screened and tentatively identified. The endogenous metabolites were mainly involved in primary bile acid, sphingolipid, linoleic acid, arachidonic acid, amino acids (alanine, aspartate, and glutamate), butanoate and glycerophospholipid metabolism in plasma, and terpenoid backbone biosynthesis, glycerophospholipid and tryptophan metabolism in urine. After LZD treatment, these markers notably restored to normal levels. The study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics, which laid a foundation for further exploring the pathological and physiological mechanism, early diagnosis, and corresponding drug development of colitis.


Exons 45-55 Skipping Using Antisense Oligonucleotides in Immortalized Human DMD Muscle Cells.
Antisense oligonucleotides (AOs) have demonstrated high potential as a therapy for treating genetic diseases like Duchene muscular dystrophy (DMD). As a synthetic nucleic acid, AOs can bind to a targeted messenger RNA (mRNA) and regulate splicing. AO-mediated exon skipping transforms out-of-frame mutations as seen in DMD into in-frame transcripts. This exon skipping approach results in the production of a shortened but still functional protein product as seen in the milder counterpart, Becker muscular dystrophy (BMD). Many potential AO drugs have advanced from laboratory experimentation to clinical trials with an increasing interest in this area. An accurate and efficient method for testing AO drug candidates in vitro, before implementation in clinical trials, is crucial to ensure proper assessment of efficacy. The type of cell model used to examine AO drugs in vitro establishes the foundation of the screening process and can significantly impact the results. Previous cell models used to screen for potential AO drug candidates, such as primary muscle cell lines, have limited proliferative and differentiation capacity, and express insufficient amounts of dystrophin. Recently developed immortalized DMD muscle cell lines effectively addressed this challenge allowing for the accurate measurement of exon-skipping efficacy and dystrophin protein production. This chapter presents a procedure used to assess DMD exons 45-55 skipping efficiency and dystrophin protein production in immortalized DMD patient-derived muscle cells. Exons 45-55 skipping in the DMD gene is potentially applicable to 47% of patients. In addition, naturally occurring exons 45-55 in-frame deletion mutation is associated with an asymptomatic or remarkably mild phenotype as compared to shorter in-frame deletions within this region. As such, exons 45-55 skipping is a promising therapeutic approach to treat a wider group of DMD patients. The method presented here allows for improved examination of potential AO drugs before implementation in clinical trials for DMD.


LoDoPaB-CT, a benchmark dataset for low-dose computed tomography reconstruction.
Deep learning approaches for tomographic image reconstruction have become very effective and have been demonstrated to be competitive in the field. Comparing these approaches is a challenging task as they rely to a great extent on the data and setup used for training. With the Low-Dose Parallel Beam (LoDoPaB)-CT dataset, we provide a comprehensive, open-access database of computed tomography images and simulated low photon count measurements. It is suitable for training and comparing deep learning methods as well as classical reconstruction approaches. The dataset contains over 40000 scan slices from around 800 patients selected from the LIDC/IDRI database. The data selection and simulation setup are described in detail, and the generating script is publicly accessible. In addition, we provide a Python library for simplified access to the dataset and an online reconstruction challenge. Furthermore, the dataset can also be used for transfer learning as well as sparse and limited-angle reconstruction scenarios.


A Botrytis cinerea emopamil binding domain protein, required for full virulence, belongs to a eukaryotic superfamily which has expanded in euascomycetes.
A previous transcriptomic analysis of 3,032 fungal genes identified the Botrytis cinerea PIE3 (BcPIE3) gene to be up-regulated early in planta (A. Gioti, A. Simon, P. Le Pêcheur, C. Giraud, J. M. Pradier, M. Viaud, and C. Levis, J. Mol. Biol. 358:372-386, 2006). In the present study, BcPIE3 was disrupted in order to determine its implication in pathogenicity. BcPIE3 was shown to be a virulence factor, since the DeltaBcPIE3 mutant was blocked during the colonization of tomato and bean leaves, giving lesions reduced in size by at least 74%. Within the emopamil binding domain (EBD), BcPIE3 shows significant structural similarities to mammalian emopamil binding proteins (EBPs). Mammalian EBPs function as sterol isomerases, but an analysis of the sterol content and the results of growth inhibition experiments with the DeltaBcPIE3 strain indicated that BcPIE3 is dispensable for ergosterol biosynthesis. The systematic identification of EBD-containing proteins included in public databases showed that these proteins constitute a protein superfamily present only in eukaryotes. Phylogenetic analysis showed that the ancestral EBD-encoding gene was duplicated in the common ancestor of animals and fungi after the split from plants. Finally, we present evidence that the EBP phylogenetic clade of this superfamily has further expanded exclusively in euascomycetes, especially in B. cinerea, which contains three copies of the EBP gene.


Multimodal Clinical Pathway With Adductor Canal Block Decreases Hospital Length of Stay, Improves Pain Control, and Reduces Opioid Consumption in Total Knee Arthroplasty Patients: A Retrospective Review.
Total knee arthroplasty volume is increasing significantly in the United States. Reducing hospital length of stay may represent the best method for accommodating expanding volume and reducing costs. We hypothesized that tailoring a clinical pathway to facilitate early ambulation would decrease costs and resource utilization. We conducted a sequential before-and-after study of total knee arthroplasty patients after a phased implementation of a clinical pathway that includes multimodal oral analgesic protocols, adductor canal nerve block, and standardized day of surgery ambulation protocols. Primary outcomes measured were hospital length of stay, total opioid consumption, total antiemetic use, and perioperative pain scores. Two hundred ninety-five patients were divided into 3 sequential cohorts. Cohort 1 received spinal anesthesia, femoral nerve block, and was not placed into postop day 0 ambulation therapy. Cohort 2 received spinal anesthesia, adductor canal block, and postop day 0 ambulation therapy. Cohort 3 received spinal anesthesia, adductor canal block, postop day 0 ambulation therapy, and standardized oral multimodal analgesic protocol. Cohort 3 had significantly reduced hospital length of stay. Cohorts 2 and 3 had significantly less opioid consumption. Cohort 3 had significantly less total ondansetron consumption compared with cohort 1. Cohort 3 had significantly reduced average pain scores compared with cohort 1. The data demonstrate that tailored clinical pathways designed to facilitate early ambulation can reduce hospital length of stay, reduce opioid consumption, reduce antiemetic use, and improve pain control. The results establish that refined clinical pathways can assist in improving care while increasing value to patients, providers, and systems.


Physicochemical properties of (1-->6)-branched (1-->3)-beta-D-glucans. 1. Physical dimensions estimated from hydrodynamic and electron microscopic data.
The physical dimensions of several (1-->6) branched (1-->3)-beta-D-glucan samples obtained from different organisms and their derivatives have been studied by electron microscopy, light scattering measurements, viscometry, and gel permeation chromatography. The electron micrographs indicate that in most samples these biopolymers are adequately described as linear worm-like coils. A sample reconstituted from alkaline media appeared as a blend of the linear, circular, and aggregated polymer morphologies. The average mass per unit length, ML = Mw/Lw for the macroscopically linear samples, was estimated to be 2100 +/- 200 g mol-1 nm-1. The parameter ML was determined from the contour lengths obtained by electron microscopy and the molecular weight by light scattering measurements. The observed ML was consistent with the triple-helical structure reported from x-ray diffraction studies and observed degree of side-chain substitution. From the molecular snapshots shown in the electron micrographs, the persistence lengths of these beta-D-glucans were determined to be 140 +/- 30 nm. The experimentally determined intrinsic viscosities were consistent with these estimates of ML and persistence length. Comparison of the molecular weight distributions obtained from gel permeation chromatography and those deduced from the electron micrographs indicates that number and weight average contour lengths are more reliable than z and z + 1 averages.


On the role of modeling choices in estimation of cerebral aneurysm wall tension.
To assess various approaches to estimating pressure-induced wall tension in intracranial aneurysms (IA) and their effect on the stratification of subjects in a study population. Three-dimensional models of 26 IAs (9 ruptured and 17 unruptured) were segmented from Computed Tomography Angiography (CTA) images. Wall tension distributions in these patient-specific geometric models were estimated based on various approaches such as differences in morphological detail utilized or modeling choices made. For all subjects in the study population, the peak wall tension was estimated using all investigated approaches and were compared to a reference approach-nonlinear finite element (FE) analysis using the Fung anisotropic model with regionally varying material fiber directions. Comparisons between approaches were focused toward assessing the similarity in stratification of IAs within the population based on peak wall tension. The stratification of IAs tension deviated to some extent from the reference approach as less geometric detail was incorporated. Interestingly, the size of the cerebral aneurysm as captured by a single size measure was the predominant determinant of peak wall tension-based stratification. Within FE approaches, simplifications to isotropy, material linearity and geometric linearity caused a gradual deviation from the reference estimates, but it was minimal and resulted in little to no impact on stratifications of IAs. Differences in modeling choices made without patient-specificity in parameters of such models had little impact on tension-based IA stratification in this population. Increasing morphological detail did impact the estimated peak wall tension, but size was the predominant determinant.


The effect of high-fidelity simulation technology on the competency of nursing students in managing chemotherapy extravasation in patients with cancer.
Nursing education suffers from a lack of high-quality clinical experiences for students, especially among medical specialty groups such as cancer patients, in Saudi Arabia. A paucity of empirical evidence is supporting simulation in education and the transfer of psychomotor skills to patient care. In particular, although generally recognized as an essential oncology nursing skill, effective strategies for teaching the management of chemotherapy extravasation to students have not been investigated. To investigate the effects of high-fidelity simulation (HFS) technology on the competency of nursing students in the management of chemotherapy extravasation and the transfer of this skill from traditional learning labs to clinical settings. A quasi-experimental study comprising a two-group pretest-posttest with repeated measures was used. The intervention was a scenario-based, HFS. Third-year students (n = 68) from a nursing program were randomly allocated to either intervention or control groups. Competency was measured in both groups using the same standardized assessment checklist. Competency scores were lower in the control group compared to the intervention group at both posttesting times. These results, however, were not statistically significant. There was no statistically significant difference between the groups regarding skill transfer. Nursing faculty can use either HFS or traditional learning methods to effectively teach students how to manage chemotherapy extravasation and transfer this skill to clinical settings.


The diversity of cell morphology in cloned cell lines derived from Drosophila imaginal discs.
We have devised a protocol for the cloning of our cell lines, and have demonstrated that a cloned line may contain cells of widely differing morphology - epithelial, fibroblast-like, and lamellocyte-like. These different morphologies must therefore represent diversity in the microenvironment of the culture rather than diversity in the cellular origin of the line.


Surveillance tools for detection of recurrent nasopharyngeal carcinoma: An evidence-based review and recommendations.
Nasopharyngeal carcinomas (NPC) are tumors arising from epithelium of the nasopharynx. The 5-year survival rate of primary NPC is 80% with significant risks of recurrence. The objective here is to provide an evidence-based systemic review of the diagnostic value of different modalities in detecting local, regional, and distal recurrent NPC, as well as the associated costs with these modalities. MEDLINE, EMBASE, and the Cochrane review database were queried. Two hundred and twenty-three abstracts were generated using the inclusion criteria: patients >18 years of age; histopathological reference standard; and modalities pertaining to imaging or microbiology. Twenty-four manuscripts fulfilled the inclusion criteria and 5 surveillance tools identified: endoscopy, MR, FDG-PET, Tc-99m MIBI and 201TI SPECT, and EBV DNA. For local surveillance, endoscopy is the gold standard recommendation, with increased efficacy if Narrow Band Imaging or contact endoscopy are utilized. MRI and FDG-PET is also recommended to help with local to distal spread; however, Tc-99m MIBI and 201TI SPECT are options as well. EBV DNA is recommended as a cheap and accessible adjunct surveillance tool if an available as an option.


Celastrol induces premature ovarian insufficiency by inducing apoptosis in granulosa cells.
Celastrol, a natural compound purified from the Chinese herb Tripterygium wilfordii Hook. f., has excellent pharmacological activity for the treatment of various diseases. Assessing the safety of its use is essential for its development into a clinical medicine. However, research assessing its toxicity on the female reproductive system has never been reported. In this study, the ovarian toxicity of celastrol and its underlying mechanism were investigated. We found that celastrol induced premature ovarian insufficiency and apoptosis in granulosa cells. Activity-based protein profiling results showed that high mobility group box 1 was a candidate target protein of celastrol. Celastrol directly bound to Cys106 of high mobility group box 1. Knocking down high mobility group box 1 induced apoptosis of granulosa cells, while overexpression of this gene reversed celastrol-induced apoptosis. Celastrol treatment upregulated p21 transcription, but overexpression of high mobility group box 1 reversed this upregulation. Thus, Celastrol induces premature ovarian insufficiency and apoptosis in granulosa cells by directly binding to high mobility group box 1 and interfering with its biological function to regulate p21 transcription. This study provides valuable information for assessing the safety of the clinical application of celastrol on female patients.


[Angina pectoris due to coronary-subclavian steal syndrome caused by the LIMA graft in the patient after CABG with the use of the right and left mammary artery].
We present a case of a patient with unstable angina pectoris two years after coronary artery by-pass graft surgery with the use of the right and left mammary artery. The symptoms were caused by the critical RIMA stenosis and coronary-subclavian steal syndrome through the LIMA graft. Unsuccessful attempt of percutaneous angioplasty of the closed left subclavian artery was made. The angioplasty of the proximal part of the RIMA with the implantation of a drug eluting stent followed by the angioplasty of both left circumflex artery and obtuse marginal artery with the implantation of bare metal stents was performed. These procedures resulted in disappearance of anginal symptoms. Neurological examination did not reveal any signs of vertebrobasilar steal.


Design preferences for global scale: a mixed-methods study of "glocalization" of an animated, video-based health communication intervention.
Designing health communication interventions for global scaling promotes health literacy and facilitates rapid global health messaging. Limited literature explores preferences for animation prototypes and other content characteristics across participants in different global regions. Prior research underscores an urgent need for health communication interventions that are compelling and accessible across culturally and geographically diverse audiences. This study presents feedback from global learners on animation design preferences and other key considerations for the development of educational video content intended for global adaptation and scaling. We used a mixed-methods, sequential explanatory design, with a qualitative descriptive approach to the analysis of the qualitative data. We recruited participants from an international group of learners enrolled in a massive open online course. Through an online quantitative survey (n = 330), we sought preferences from participants in 73 countries for animation design prototypes to be used in video-based health communication interventions. To learn more about these preferences, we conducted in-depth interviews (n = 20) with participants selected using maximum variation purposive sampling. Generally, respondents were willing to accept animation prototypes that were free of cultural and ethnic identifiers and believed these to be preferable for globally scalable health communication videos. Diverse representations of age, gender roles, and family structure were also preferred and felt to support inclusive messaging across cultures and global regions. Familiar-sounding voiceovers using local languages, dialects, and accents were preferred for enhancing local resonance. Across global regions, narratives were highlighted as a compelling approach to facilitating engagement and participants preferred short videos with no more than two or three health messages. Our findings suggest that global learners may be willing to accept simplified visuals, designed for broad cross-cultural acceptability, especially if the content is localized in other ways, such as through the use of locally resonating narratives and voiceovers. Diverse, inclusive portrayals of age, gender roles and family structure were preferred.


A unique mechanism of restenosis after drug-coated balloon in peripheral artery: Insight from optical frequency domain imaging.
Drug-coated balloons (DCBs) have been widely used in endovascular therapy for femoropopliteal arteries with atherosclerotic lesions. Vascular response after DCBs remains unclear. This mini-review proposes a possible mechanism of restenosis after the DCB strategy. Balloon dilatation including DCBs expands the vascular lumen by producing dissections, which is composed of the original vascular lumen and the cavity surrounded by dissected flaps. The cavity surrounded by dissected flaps is eventually replaced with the thrombus in the healing process after balloon dilatation. However, the thrombus may propagate to the expanded vascular lumen through the entry point of the dissection. Subsequently, the thrombus both in the cavity and the expanded lumen would be organized over time. The vascular lumen in the chronic-phase after DCBs may be influenced by the propagated thrombus from the cavity surrounded by dissected flaps.


Correlations among capillaroscopic abnormalities, digital flow and immunologic findings in patients with isolated Raynaud's phenomenon. Can laser Doppler flowmetry help identify a secondary Raynaud phenomenon?
Thirty subjects with a diagnosis of isolated Raynaud's phenomenon, according to anamnestic and objective criteria, were cross-evaluated by various methods: laser Doppler flowmetry (LDF) during a standardized cold and rewarming test, nailfold capillaroscopy, immunological and other laboratory parameters, to assess the diagnostic and prognostic significance of each method. Correlations were also assessed among disease duration, capillaroscopic pattern score, quantitative digital flow values and laboratory parameters. Nearly 30% of patients showed immunologic abnormalities (ANA positivity at variable titres, ENA, hypocomplementemia, immunocomplexes); 16% of patients had a pathologic capillaroscopic pattern, not well correlated with immunologic findings; a characteristic cold stop reaction of digital flow (partial or total) was detected in 86% of the subjects; in ANA+ pts., ANA titers were positively correlated with the intensity and length of stop reaction (Trec). A significant correlation between digital flow parameters and the capillaroscopic score was also found in each considered group. Our results outline the relevance of LDF, during a standardized thermic test, to evaluate apparently primary RP, because even if a definite scleroderma-like capillaroscopic pattern is absent, this flowmetric method may detect potentially secondary RP patients.


Screen design and visual evoked potentials.
In this paper we present a method to complement the sophisticated mathematical analyses on screen designs. The use of an objective measure of screen "goodness" is employed, namely, the Visual Evoked Potential (VEP) of the humans performing the test. After the screen is designed, the text on the screen is transformed into an intensity pattern using a recursive algorithm. This intensity pattern is used as a stimulus to obtain wave forms from the scalp of the subject, and the wave forms are analyzed as to their frequency content. A 2-D Fourier transform of the screen design is performed and the frequency components of the power spectrum are compared to the frequency components of the wave form. Our results indicate that when a "balanced" and well-designed screen is used as a stimulus, the second harmonic of the VEP wave form is always smaller than the first harmonic. The implications of such an analysis are discussed.


Experimental cardiovascular depressant effects of garlic (Allium sativum) dialysate.
The objectives of this work were to investigate the effects of a garlic dialysate on diastolic blood pressure (DBP), heart rate (HR) and electrocardiogram (ECG) of anaesthetized dogs and its effects on frequency and tension of isolated rat atria. Garlic dialysate led to a drop in DBP (from 112.5 +/- 3.67 to 70 +/- 3.16 mmHg) and a decrease in HR (from 198 +/- 9.81 to 164 +/- 16.59 beats/min) in a dose-dependent manner. The ECG showed a regular sinus bradycardic rhythm. The addition of garlic dialysate to isolated left rat atria evoked a decrease in tension development. Frequency, measured by spontaneous beating of the right atria, was also reduced. Both effects were dose-dependent. In addition to these effects, the positive inotropism and chronotropism induced by addition of isoproterenol 10(-9) M, were partially antagonized by preincubation of the rat atria with the garlic dialysate. The above findings can be explained by a depressant effect on automaticity and tension development in the heart, suggesting a beta-adrenoceptor blocking action produced by the garlic dialysate.


Controlled indole-3-acetaldoxime production through ethanol-induced expression of CYP79B2.
Indole-3-acetaldoxime (IAOx) is a key branching point between primary and secondary metabolism. IAOx serves as an intermediate in the biosynthesis of indole glucosinolates (I-GLSs), camalexin and the plant hormone indole-3-acetic acid (IAA). The cytochrome P450s CYP79B2 and CYP79B3 catalyze the conversion of tryptophan to IAOx. CYP83B1 channels IAOx into I-GLS biosynthesis, CYP71A13 channels IAOx into camalexin biosynthesis, whereas the IAOx-metabolizing enzyme in IAA biosynthesis is not known. In this report, we demonstrate controlled production of I-GLSs by introducing an ethanol (EtOH)-inducible CYP79B2 construct into double (cyp79b2 cyp79b3) or triple (cyp79b2 cyp79b3 cyp83b1) mutant lines. We show EtOH-dependent induction of camalexin and identify a number of candidate IAA homeostasis- or defense-related genes by clustered microarray analysis. The transgenic mutant lines are thus promising tools for elucidating the interplay between primary and secondary metabolism.


A novel fluorescence ratio probe based on dual-emission carbon dots for highly selective and sensitive detection of chlortetracycline and cell imaging.
The novel dual-emission carbon dots (DECDs) for highly selective and sensitive recognition of chlortetracycline (CTC) and cell imaging were synthesized successfully by one-step synthesis. The obtained DECDs possessed two fluorescence peaks (345 nm and 450 nm) and showed specific response to CTC, resulting in a decrease in fluorescence intensity at 345 nm, a blue shift, and an increase in fluorescence intensity at 450 nm. The obtained DECDs exhibited highly selective response to CTC and not to its analogues, such as tetracycline, doxycycline, and oxytetracycline. Thus, an excellent ratiometric probe for the detection of CTC was fabricated successfully and used for the detection of CTC in real samples with the detection limit (LOD) of 16.45 nM. More importantly, the DECDs were used for quantitative detection of CTC in living cells, which demonstrated excellent biocompatibility and broad prospects in biomedicine application. Finally, the excellent selectivity of DECDs toward CTC was attributed to the FRET mechanism and the formation of complexes.


The impact of PRODIGE 7 on the current worldwide practice of CRS-HIPEC for colorectal peritoneal metastases: A web-based survey and 2021 statement by Peritoneal Surface Oncology Group International (PSOGI).
The PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC. CRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7. The survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate. The PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated.


Technique of right lymphatic duct cannulation for pulmonary lymph collection in an acute porcine model.
The pig is an increasingly preferred model for biomedical research, including studies for pulmonary pathophysiology. However, in piglets, the technique for cannulating the right lymphatic duct, which is subject to more anatomical variations and technically more demanding than that in dogs, has not been described. Our technique evolved to enable this collection of porcine lung lymph in acute experiments. The lymphatic ampulla is cannulated via one of the cervical lymphatics. The right lymphatic duct is invariably dorsal to the cranial vena cava and classically leads to the lymphatic ampulla. Yet in 18% of our pigs, cannulation was difficult or not feasible because the lymphatic duct either drained directly into the cranial vena cava at a distance from the lymphatic ampulla, or into the axillary lymph node of the first rib or the caudal deep cervical lymph nodes. Gently squeezing back regurgitated blood in the lymphatic ampulla before tying the suture and frequently withdrawing lymph with a syringe when the flow is small enabled us to collect clear lymph, usually immediately after completing the cannulation. The rate of lymph flow varied widely (1.7 +/- 0.6 ml/hr) and increased when the left atrial pressure was raised. The lymph protein was 2.8 +/- 0.2 g% with lymph/plasma protein ratio at 0.55 +/- 0.04. The anatomical variations encountered in our 34 dissections, as well as the technical maneuvers found to be useful in the successful cannulation and collection of the porcine lung lymph, are described in detail.


Exome sequencing in obsessive-compulsive disorder reveals a burden of rare damaging coding variants.
Obsessive-compulsive disorder (OCD) affects 1-2% of the population, and, as with other complex neuropsychiatric disorders, it is thought that rare variation contributes to its genetic risk. In this study, we performed exome sequencing in the largest OCD cohort to date (1,313 total cases, consisting of 587 trios, 41 quartets and 644 singletons of affected individuals) and describe contributions to disease risk from rare damaging coding variants. In case-control analyses (n = 1,263/11,580), the most significant single-gene result was observed in SLITRK5 (odds ratio (OR) = 8.8, 95% confidence interval 3.4-22.5, P = 2.3 × 10-6). Across the exome, there was an excess of loss of function (LoF) variation specifically within genes that are LoF-intolerant (OR = 1.33, P = 0.01). In an analysis of trios, we observed an excess of de novo missense predicted damaging variants relative to controls (OR = 1.22, P = 0.02), alongside an excess of de novo LoF mutations in LoF-intolerant genes (OR = 2.55, P = 7.33 × 10-3). These data support a contribution of rare coding variants to OCD genetic risk.


Trends in amyloidosis in spondyloarthritis: results from the Spanish National Inpatient Registry over a 17-year period (1999-2015)-TREND-EspA study.
To assess the incidence of amyloidosis and trends therein in patients with spondyloarthritis (SpA) over a long period (17 years). An observational retrospective population-based matched cohort study was conducted. All the admissions of patients with SpA, including ankylosing spondylitis (AS), psoriatic arthritis (PsA), arthritis associated with inflammatory bowel disease (SpA-IBD) and reactive arthritis (ReA), reported between 1999 and 2015, were analysed and a control group matched by age, sex and year of admission was selected. Incidence rates for amyloidosis were calculated. Generalised linear models were used for trend analysis and unconditional logistic regression for calculating crude and adjusted ORs (AOR) to assess the association between amyloidosis and SpA. The study database contained data on 107 140 admissions in each group. Between 1999 and 2015, 792 patients in the SpA cohort (0.7% of all admissions) had a diagnosis of amyloidosis versus 68 in the non-SpA cohort (0.1%) (p<0.001). From 1999 to 2015, incidence rates of amyloidosis tended to decrease in the SpA cohort (-4.63%/year overall), while they increased in the Non-SpA cohort (+10.25%/year overall). We found strong associations of amyloidosis with all SpAs (AOR 10.4; 95% CI 8.2 to 13.3) and with each type studied (AORs 10.05 (7.84 to 12. 88) for AS, 9.5 (7.3 to 12.4) for PsA, 22.9 (16.6 to 31.7) for SpA-IBD and 10.1 (6.1 to 16.7) for ReA). Incidence of amyloidosis among patients with SpA has strongly decreased in Spain. Amyloidosis is most strongly associated with SpA-IBD while the strength of association with PsA and ReA is similar to that with AS.


Resource productivity and environmental degradation in EU-27 countries: context of material footprint.
This study explores the relationship between the resource productivity and environmental degradation in European Union-27 countries. This study tests this relationship in context of high, moderate, and low material footprint sub-samples; these samples are formed utilizing the expectation-maximization machine learning algorithm. Using the panel data set of EU-27 countries from 2000 to 2020, linear and non-linear autoregressive distributed lag (ARDL) are applied for the symmetric and asymmetric evidence and to test environmental Kuznets curve (EKC), linear ARDL with the quadratic function is included. Results of the symmetric relationship find evidence of resource productivity's impact on the environmental degradation. In full sample of EU-27, both symmetric and asymmetric methods show that the short run and long run increase of resource productivity lower the environmental degradation. Only long run asymmetric relationship in high material footprint subsamples supports that the resource productivity controls environmental degradation. Results of moderate material footprint sub-sample are mixed. However, low material footprint countries show that resource productivity in long run controls the environmental degradation in symmetry and only positive resource controls productivity in short run in asymmetric relationship. The reason for mixed results is the quadratic nature of sub-samples. EKC hypothesis is validated in moderate and low material footprint sub-samples. This research has many policy implications.


Bilateral Lambdoid and Sagittal Craniosynostosis with Hydrocephalus: ETV, Bifrontal Craniotomy, Anterior Cranial Vault Remodeling, and Posterior Cranial Vault Expansion.
Bilateral lambdoid and sagittal craniosynostosis (BLSS), also known as Mercedes Benz pattern craniosynostosis, is a rare form of craniosynostosis. The whole cranial vault remodeling gives the best result. To describe the role of endoscopic third ventriculostomy (ETV) and whole cranial vault remodeling for treatment of BLSS. Surgical technique/procedure: A single-sitting three-step surgery was performed for a 7-month-old child who had BLSS and hydrocephalus. First ETV and anterior cranial vault remodeling were done in the supine position. The posterior cranial vault expansion was done in the prone position. The ventricle volume reduced at follow-up and the frontal bossing also reduced. The whole cranial vault remodeling gives the best result for BLSS.


Usefulness of a multiplex immunodot in case of discordant results between automated COVID-19 serological assays.
At present, the only reliable test for COVID-19 diagnosis is RT-qPCR. Serological assays have been widely used to increase the detection sensitivity of infected population. Hereby, we report the performance of a new pan-IgG multiplex Enzyme Immunoassay (immunodot) method for exploration of discrepant SARS-COV-2 serological results. A retrospective study on 38 residual serum samples from recovered COVID-19 subjects with discordant serological results on Roche and Snibe platforms, were reanalyzed on a new semi-automated pan-IgG immunodot Enzyme Immunoassay, namely COVIDOT-TEST, in order to find the source of discrepancies and to evaluate the latter method. All samples were analyzed on the BlueDiver® Instrument and all strips were read by the BlueScan® Scanner using Dr DOT® Software. Based on our data, subject samples showed specific IgG reactions on ≥ 2 different antigens on immunodot strips. Of these 38 samples, 97.4 % of samples showed specific IgG reaction against S1 + S2 antigens, 89.5 % showed against RBD antigen, 86.8 % against S2 antigen reaction on the COVIDOT-TEST kit. Specific IgG-S1 antigen and IgG-N antigen reactions were detected in 73.7 % and 65.8 % of the samples, respectively. The new semi-automated pan-IgG immunodot Enzyme Immunoassay method appeared to be a reliable assay to confirm suspicious COVID-19 serological screening results.


Mucociliary Clearance Differs in Mild Asthma by Levels of Type 2 Inflammation.
Although mucus plugging is a well-reported feature of asthma, whether asthma and type 2 inflammation affect mucociliary clearance (MCC) is unknown. Does type 2 inflammation influence mucus clearance rates in patients with mild asthma who are not receiving corticosteroids? The clearance rates of inhaled radiolabeled particles were compared between patients with mild asthma with low (n = 17) and high (n = 18) levels of T2 inflammation. Fraction exhaled nitric oxide (Feno) was used to prospectively segregate subjects into T2 Lo (Feno < 25 ppb) and T2 Hi (Feno > 35 ppb) cohorts. Bronchial brush samples were collected with fiber-optic bronchoscopy, and quantitative polymerase chain reaction was performed to measure expression of genes associated with T2 asthma. MCC rate comparisons were also made with a historical group of healthy control subjects (HCs, n = 12). The T2 Lo cohort demonstrated increased MCC when compared with both T2 Hi and historic HCs. MCC within the T2 Hi group varied significantly, with some subjects having low or zero clearance. MCC decreased with increasing expression of several markers of T2 airway inflammation (CCL26, NOS2, and POSTN) and with Feno. MUC5AC and FOXJ1 expression was similar between the T2Lo and T2Hi cohorts. Increasing T2 inflammation was associated with decreasing MCC. High rates of MCC in T2 Lo subjects may indicate a compensatory mechanism present in mild disease but lost with high levels of inflammation. Future studies are required to better understand mechanisms and whether impairments in MCC in more severe asthma drive worse clinical outcomes.


Variable restricted feeding disrupts the daily oscillations of Period2 expression in the limbic forebrain and dorsal striatum in rats.
Predictable restricted feeding schedules limit food availability to a single meal at the same time each day, lead to the induction and entrainment of circadian rhythms in food-anticipatory activity, and shift daily rhythms of clock gene expression in areas of the brain that are important in the regulation of motivational and emotional state. In contrast, when food is delivered under a variable restricted feeding (VRF) schedule, at a new and unpredictable mealtime each day, circadian rhythms in food-anticipatory activity fail to develop. Here, we study the effects of VRF on the daily rhythm of plasma corticosterone and of clock gene expression in the limbic forebrain and dorsal striatum, of rats provided a 2-h access to a complete meal replacement (Ensure Plus) at an unpredictable time each day. VRF schedules varied the mealtimes within the 12 h of light (daytime VRF), the 12 h of dark (nighttime VRF), or across the 24 h light-dark cycle (anytime VRF). Our results show that contrary to the synchronizing effects of predictable restricted feeding, VRF blunts the daily corticosterone rhythm and disrupts daily rhythms of PER2 expression in a region-specific and mealtime-dependent manner.


Customer Analysis Using Machine Learning-Based Classification Algorithms for Effective Segmentation Using Recency, Frequency, Monetary, and Time.
Customer segmentation has been a hot topic for decades, and the competition among businesses makes it more challenging. The recently introduced Recency, Frequency, Monetary, and Time (RFMT) model used an agglomerative algorithm for segmentation and a dendrogram for clustering, which solved the problem. However, there is still room for a single algorithm to analyze the data's characteristics. The proposed novel approach model RFMT analyzed Pakistan's largest e-commerce dataset by introducing k-means, Gaussian, and Density-Based Spatial Clustering of Applications with Noise (DBSCAN) beside agglomerative algorithms for segmentation. The cluster is determined through different cluster factor analysis methods, i.e., elbow, dendrogram, silhouette, Calinsky-Harabasz, Davies-Bouldin, and Dunn index. They finally elected a stable and distinctive cluster using the state-of-the-art majority voting (mode version) technique, which resulted in three different clusters. Besides all the segmentation, i.e., product categories, year-wise, fiscal year-wise, and month-wise, the approach also includes the transaction status and seasons-wise segmentation. This segmentation will help the retailer improve customer relationships, implement good strategies, and improve targeted marketing.


Channelling auxin action: modulation of ion transport by indole-3-acetic acid.
The growth hormone auxin is a key regulator of plant cell division and elongation. Since plants lack muscles, processes involved in growth and movements rely on turgor formation, and thus on the transport of solutes and water. Modern electrophysiological techniques and molecular genetics have shed new light on the regulation of plant ion transporters in response to auxin. Guard cells, hypocotyls and coleoptiles have advanced to major model systems in studying auxin action. This review will therefore focus on the molecular mechanism by which auxin modulates ion transport and cell expansion in these model cell types.


1-Butyl-3-(1-naphtho-yl)-1H-indole.
In the title mol-ecule, C(23)H(21)NO, the dihedral angle between the planes of the indole ring and naphthalene ring system is 68.8 (5)°.


High tax on high energy dense foods and its effects on the purchase of calories in a supermarket. An experiment.
The present study examined whether a high tax on high calorie dense foods effectively reduces the purchased calories of high energy dense foods in a web based supermarket, and whether this effect is moderated by budget and weight status. 306 participants purchased groceries in a web based supermarket, with an individualized budget based on what they normally spend. Results showed that relative to the no tax condition, the participants in the tax condition bought less calories. The main reduction was found in high energy dense products and in calories from carbohydrates, but not in calories from fat. BMI and budget did not influence the effectiveness of the tax. The reduction in calories occurred regardless of budget or BMI implying that a food tax may be a beneficial tool, along with other measures, in promoting a diet with fewer calories.


Pilot study on the value of echocardiography combined with lung ultrasound to evaluate COVID-19 pneumonia.
This study aimed to investigate the relationship between echocardiography results and lung ultrasound score (LUS) in coronavirus disease 2019 (COVID-19) pneumonia patients and evaluate the impact of the combined application of these techniques in the evaluation of COVID-19 pneumonia. Hospitalized COVID-19 pneumonia patients who underwent daily lung ultrasound and echocardiography were included in this study. Patients with tricuspid regurgitation within three days of admission were enrolled. Moreover, the correlation and differences between their pulmonary artery pressure (PAP) and LUS on days 3, 8, and 13 were analyzed. The inner diameter of the pulmonary artery root as well as the size of the atria and ventricles were also considered. The PAP on days 3, 8, and 13 of hospitalization was positively correlated with the LUS (r = 0.448, p = 0.003; r = 0.738, p < 0.001; r = 0.325, p = 0.036, respectively). On day 8, the values of both PAP and LUS were higher than on days 3 and 13 (p < 0.01). Similarly, PAP and LUS were significantly increased in 92.9% (39/42) and 90.5% (38/42) of patients, respectively, and at least one of these two values was positive in 97.6% (41/42) of cases. The inner diameters of the right atrium, right ventricle, and pulmonary artery also differed significantly from their corresponding values on days 3 and 13 (p < 0.05). PAP is positively correlated with LUS in COVID-19 pneumonia. The two values could be combined for a more precise assessment of disease progression and recovery status.


Effect of sauna-based heat acclimation on plasma volume and heart rate variability.
We investigated the effect of post-exercise sauna bathing on plasma volume (PV) expansion and whether such responses can be tracked by changes in heart rate (HR)-based measures. Seven, well-trained male cyclists were monitored for 35 consecutive days (17 days baseline training, 10 days training plus sauna, 8 days training). Sauna exposure consisted of 30 min (87 °C, 11 % relative humidity) immediately following normal training. Capillary blood samples were collected while resting seated to assess PV changes. HR (HRwake) and vagal-related HR variability (natural logarithm of square root mean squared differences of successive R-R intervals, ln rMSSDwake) were assessed daily upon waking. A sub-maximal cycle test (5 min at 125 W) was performed on days 1, 8, 15, 22, 25, 29, and 35 and HR recovery (HRR60s) and ln rMSSDpostex were assessed post-exercise. Effects were examined using magnitude-based inferences. Compared with baseline, sauna resulted in: (1) peak PV expansion after four exposures with a likely large increase [+17.8 % (90 % confidence limits, 7.4; 29.2)]; (2) reduction of HRwake by a trivial-to-moderate amount [-10.2 % (-15.9; -4.0)]; (3) trivial-to-small changes for ln rMSSDwake [4.3 % (1.9; 6.8)] and ln rMSSDpostex [-2.4 % (-9.1; 4.9)]; and (4) a likely moderate decrease in HRR60s [-15.6 % (-30.9; 3.0)]. Correlations between individual changes in PV and HR measures were all unclear. Sauna bathing following normal training largely expanded PV in well-trained cyclists after just four exposures. The utility of HR and HRV indices for tracking changes in PV was uncertain. Future studies will clarify mechanisms and performance benefits of post-training sauna bathing.


Silk protein sericin pretreatment enhances osmotic tolerance and post-thaw sperm quality but reduces the ability of sperm cells to undergo in vitro induced acrosome reaction in rabbit.
Effect of sericin pretreatment of sperm cells on the osmotic tolerance, ability to undergo acrosome reaction induced by calcium ionophore (CI), heparin (H) or lysophosphatidylcholine (LPC), post-thaw sperm quality and in vivo fertility was evaluated in four successive experiments in rabbit. In experiment 1, fresh semen was pretreated with sericin (0, 0.1% or 0.5% w/v) before exposing to fructose solutions adjusted to either 50, 100, 290, 500 or 1000 mOsm/L. Sericin pretreatment increased sperm livability in addition to live-membrane intact and total membrane intact sperm rates (P < 0.05) in 50 and 290 mOsm/L groups. In experiment 2, sperm samples were pretreated by either 0.1 or 0.5% sericin after removal of the semen plasma. CI, H or LPC were used to induce acrosome reaction in pretreated sperm samples. Sericin pretreatment, reduced the ability of sperm cells to undergo acrosome reaction (P < 0.05) in vitro. In experiment 3, ejaculates were frozen with or without sericin pretreatment in DMSO-sucrose extender. In post-thaw samples sericin pretreatment improved total and progressive motility, livability, membrane and acrosome integrity in a dose dependent manner (P < 0.05). In vivo fertility trials by artificial inseminations revealed contradictory results in experiment 4. Although 0.5% sericin pretreatment totally inhibited fertility, 0.1% sericin provided high pregnancy rates. In conclusion; sericin pretreatment enhances osmotic tolerance and post-thaw sperm quality, but reduces the ability of rabbit sperm cells to undergo in vitro induced acrosome reaction, but this effect is restored in vivo by dose dependent manner.


Structural features of eyelid connective tissue in patients with primary open-angle glaucoma.
To study the connective tissue (CT) structure of upper eyelid skin of primary open-angle glaucoma (POAG) patients. Forty-seven patients aged 47-91 expecting blepharoplasty formed 3 groups: group 1 [16 subjects without POAG, median age 55 years (interquartile range 54-55.5)], group 2 [12 subjects without POAG, median age 73 (72-76.5)], and group 3 [(19 subjects with POAG, median age 74 (70-80.5)]. Age differences between groups 1 and 2 and groups 1 and 3 are significant (p < 0.05). Thermodynamic parameters of skin samples taken during blepharoplasty: Endothermic peak ([Formula: see text], °C) and denaturation enthalpy ([Formula: see text], J/g of dry weight) were determined using differential scanning calorimetry. [Formula: see text] and [Formula: see text] in groups 1-3 were, respectively, 8.41 (7.42-10.25) and 66.55 (59.9-66.7); 7.10 (5.76-10.17) and 67.35 (67.0-68.03); 11.40 (9.0-14.9) and 67.70 (67.05-68.45). [Formula: see text] differences between groups 1 and 2 are significant (p < 0.05), and Spearman's correlation between the age and [Formula: see text] is direct, medium (R = 0.638) and significant. [Formula: see text] in group 3 is significantly higher than in group 2. [Formula: see text] and [Formula: see text] in patients without POAG (groups 1 and 2) and those with POAG (group 3) are, respectively, 7.79 (6.9-10.17) and 66.6 (61.2-67,3); 11.40 (9.0-14.9); 67.7 (67.05-68.45); the respective differences are significant. Patients without POAG show a significant increase in [Formula: see text] with age, while [Formula: see text] slightly decreases. In POAG, [Formula: see text] is significantly higher and [Formula: see text] tends to grow, which may indicate structural changes in eyelid CT (collagen accumulation and cross-linking level rise). Since the upper lid is unaffected by increasing IOP directly, the changes may be viewed as manifestations of systemic CT pathology.


Molecular characterization of goose-type lysozyme homologue of large yellow croaker and its involvement in immune response induced by trivalent bacterial vaccine as an acute-phase protein.
Lysozyme acts as an innate immunity molecule against the invasion of bacterial pathogens. Here, the cDNA of a goose-type lysozyme (g-lysozyme) was cloned from large yellow croaker (Pseudosciana crocea) by expressed sequence tags (EST) and RACE-PCR techniques. The full-length cDNA of large yellow croaker g-lysozyme (LycGL) is 716 nucleotides (nt) encoding a protein of 193 amino acids (aa), with a theoretical molecular weight of 21.3kDa. The deduced LycGL possessed the typical structural features of g-lysozyme, including three catalytic residues (E71, D84, D101) and four substrate binding sites (L97, L121, L128, G152). Genomic analysis revealed that the LycGL gene consisting of 2383nt, contained five exons interrupted by four introns and exhibited a similar exon-intron organization to its homologues in Japanese flounder and Chinese perch, except for having a much longer intron 1 in the LycGL gene. Recombinant LycGL produced in Pichia pastoris exhibited obvious lytic activity against Micrococcus lysodeikticus and several fish pathogenic bacteria such as Aeromonas sobria, Vibrio alginolyticus, Vibrio parahaemolyticus and Vibrio vulnficus. Tissue expression profile analysis showed that LycGL mRNA was constitutively expressed in all tissues examined, such as spleen, head kidney, intestine, liver, gills and heart, although at a different level. Upon stimulation with trivalent bacterial vaccine, LycGL mRNA levels in intestine, spleen and head kidney were quickly up-regulated and had 10.32-, 10.2- and 8.26-fold increases, respectively, and LycGL transcripts in intestine and head kidney reached their peak levels at 24h post-induction and then decreased gradually while LycGL mRNA in spleen increased to its highest level at 48h. These results suggest that LycGL may be involved in antibacterial immune response activated by bacterial vaccine as an acute-phase molecule.


A novel virtual point detector model for high purity germanium detectors.
A novel virtual point detector model was developed for cylindrical high purity germanium detectors that are widely used in gamma-ray spectrometry. According to this model, the full energy peak efficiency response of these detectors can be computed by replacing the detector with a virtual point detector located at the center of the detector crystal. In fact, the novel model makes the transfer of the FEP efficiency response from a reference point source to a given point source, both sources being located on a line that passes through the virtual point detector. The model was tested and provided accurate results.


Unexpected bronchospasm during spinal anesthesia.
Asthma and bronchospastic disease are common in patients presenting for anesthesia. Intraoperative bronchospasm can be a life-threatening problem. One approach to these patients is to use regional anesthesia because it is believed that this will reduce the complication rate. Presented here is a case of bronchospasm occurring during regional anesthesia that was unresponsive to beta agonists. The use of atropine in the treatment of bronchospasm also is discussed.


Isolation and characterization of proteolytic fragments of the sea urchin sperm receptor that retain species specificity.
The sea urchin sperm receptor isolated from the eggs of Strongylocentrotus purpuratus is a high molecular weight proteoglycan-like molecule. Previous studies in our laboratory suggested that the sperm receptor has two functional components, glycosaminoglycan chains that are responsible for sperm binding and polypeptide chains that control species specificity in the binding process. We have investigated this idea further by generating fragments of the receptor by limited proteolytic digestion of the egg cell surface. The results of experiments with these receptor preparations support the hypothesis that the species specificity of inhibition of fertilization observed in a competitive bioassay is conferred by the polypeptide portion of the receptor molecule. Studies with various receptor preparations reveal that the presence of at least 30% of the polypeptide by weight is required to inhibit fertilization species specifically. Receptor preparations containing less than 10% protein lack species specificity and inhibit fertilization in both S. purpuratus and Arbacia punctulata.


Erratum: Childhood maltreatment and its relation with depression and anxiety among psychiatric patients in Riyadh - KSA.
[This corrects the article on p. 2603 in vol. 11, PMID: 36119182.].


[Care and implications for caregivers of surgical patients at home].
To identify the care given by informal caregivers to patients who underwent abdominal surgery in the Consorci Hospitalari of Vic (Barcelona). To compare the responsibility burden for those caregivers in all the different stages of the surgical process. To determine the consequences of the care itself on the caregiver's health and to identify the factors that contribute to the need of providing care and the appearance of consequences for the caregivers in the home. A longitudinal observational study with follow-up at admission, at discharge and 10 days, of 317 non-paid caregivers of patients who suffer underwent surgery. The characteristics of caregivers and surgical patients were studied. The validated questionnaire, ICUB97-R based on the model by Virginia Henderson, was used to measure the care provided by informal caregivers and its impact on patient quality of life. Most of the caregivers were women, with an average age of 52.9±13.7 years without any previous experience as caregivers. The greater intensity of care and impact was observed in the time when they arrived home after hospital discharge (p<0.05). The predictive variables of repercussions were being a dependent patient before the surgical intervention (β=2.93, p=0.007), having a cancer diagnosis (β=2.87, p<.001) and time dedicated to the care process (β=0.07, p=0.018). Caregivers involved in the surgical process provide a great amount of care at home depending on the characteristics of patients they care for, and it affects their quality of life.


Studies on the generation and expression of H-2-controlled T helper function in chimeric mice: evidence for two levels of H-2 resitriction.
F1 leads to parental, semisyngeneic/semiallogeneic and fully allogeneic bone marrow radiation chimeras were used as a source of helper T cells in the in vitro anamnestic response to dinitrophenylated keyhole limpet hemocyanin. In F1 leads to parental and in semisyngeneic/semiallogeneic chimeras, a small population of helper T cells restricted to the H-2 haplotype present in the donor only was shown to co-exist with T cells restricted to the shared haplotype. Only the population restricted to the donor H-2 could be demonstrated in allochimeras, presumably due to a lack of antigen-presenting cells of host origin during priming. Under assay conditions where, in addition to T cell/macrophage interactions, a direct T-B cell contact was necessary ("linked" cooperation), the H-2 restrictions observed were absolute. When direct T-B cell contact was made unnecessary by a special experimental protocol ("unlinked" cooperation), H-2 restriction between T and B cells was overcome. Thus, the cellular interactions during the anamnestic immune response to T-dependent antigens seem to be H-2-restricted at two levels: T cell/macrophage and T-B cell interactions.


The lunatohamate articulation of the midcarpal joint.
Sixty-one cadaveric wrists were dissected to assess the frequency of a medial lunate facet as well as any associated pathologic changes in the midcarpal joint. Two types of lunate were identified: Type I (39.3%), in which no medial facet was present, and Type II (60.7%), in which there was a medial facet. The medial facets in the Type II lunates ranged from a shallow 2 mm facet to a deep 6 mm facet. Significant cartilage erosion with exposed subchondral bone at the proximal pole of the hamate, which was not identifiable by radiograph, was evident at dissection in 57% of the Type II lunates, whereas none (0%) of the Type I lunates had such associated hamate pathology. Midcarpal joint arthroscopy appears to be the diagnostic procedure of choice to assess the presence of hamate proximal pole arthrosis.


Evaluation of surgical procedures for bilharzial strictures of the ureter.
A series of 35 patients, with unilateral hydronephrosis complicating bilharzial stricture of either the upper or the middle third of the ureter, was divided into 2 groups. Group A, comprising 21 patients, was treated by resection anastomosis. Group B, comprising 14 patients, was treated by other reparative procedures without resection of the stricture. The results of the surgical correction, assessed clinically and radiologically, showed that significantly better results were achieved with resection anastomosis than with the other procedures.


The severity of reaction after food challenges depends on the indication: A prospective multicenter study.
There are expanding indications for oral food challenges (OFCs). Although several studies have examined the risk of OFCs, little has been reported on allergic reactions during OFCs depending on the indication. This study assessed the prevalence, severity, and treatment of allergic reactions depending on the indication for OFCs. We performed a prospective multicenter study between March 2012 and May 2013. Severity of symptoms elicited by OFCs was classified according to grading of anaphylaxis that ranges from grade 1 (most mild) to grade 5 (most severe). A total of 5062 cases (median age, 3.8 years; males, 65.2%) were analyzed. Allergic reactions were elicited in 2258 (44.6%) OFCs, of which 991 (43.9%) were classified as grade 1, 736 (32.6%) were classified as grade 2, 340 (15.1%) were classified as grade 3, and 191 (8.5%) were classified as grade 4-5. Epinephrine was administered in 7.1% (n = 160) of positive OFCs. Among the top three most common food allergens (hen's egg, cow's milk, and wheat), severity differed significantly depending on the indication for OFC, and adjusted standardized residuals indicated that severity of allergic reactions was higher for the indication to assess threshold level for oral immunotherapy. In addition, the prevalence of epinephrine use was highest for the indication to determine safe intake quantity. Our study suggested that prevalence, severity, and treatment of allergic reactions differ depending on the indication for OFC. Further studies are needed to determine differences in risks depending on the indication for OFC.


A social niche breadth score reveals niche range strategies of generalists and specialists.
Generalists can survive in many environments, whereas specialists are restricted to a single environment. Although a classical concept in ecology, niche breadth has remained challenging to quantify for microorganisms because it depends on an objective definition of the environment. Here, by defining the environment of a microorganism as the community it resides in, we integrated information from over 22,000 environmental sequencing samples to derive a quantitative measure of the niche, which we call social niche breadth. At the level of genera, we explored niche range strategies throughout the prokaryotic tree of life. We found that social generalists include opportunists that stochastically dominate local communities, whereas social specialists are stable but low in abundance. Social generalists have a more diverse and open pan-genome than social specialists, but we found no global correlation between social niche breadth and genome size. Instead, we observed two distinct evolutionary strategies, whereby specialists have relatively small genomes in habitats with low local diversity, but relatively large genomes in habitats with high local diversity. Together, our analysis shines data-driven light on microbial niche range strategies.


Identification of gaze pattern and blind spots by upper gastrointestinal endoscopy using an eye-tracking technique.
The lesion detection rate of esophagogastroduodenoscopy (EGD) varies depending on the degree of experience of the endoscopist and anatomical blind spots. This study aimed to identify gaze patterns and blind spots by analyzing the endoscopist's gaze during real-time EGD. Five endoscopists were enrolled in this study. The endoscopist's eye gaze tracked by an eye tracker was selected from the esophagogastric junction to the second portion of the duodenum without the esophagus during insertion and withdrawal, and then matched with photos. Gaze patterns were visualized as a gaze plot, blind spot detection as a heatmap, observation time (OT), fixation duration (FD), and FD-to-OT ratio. The mean OT and FD were 11.10 ± 11.14 min and 8.37 ± 9.95 min, respectively, and the FD-to-OT ratio was 72.5%. A total of 34.3% of the time was spent observing the antrum. When observing the body of the stomach, it took longer to observe the high body in the retroflexion view and the low-to-mid body in the forward view. It is necessary to minimize gaze distraction and observe the posterior wall in the retroflexion view. Our results suggest that eye-tracking techniques may be useful for future endoscopic training and education.


Risk factors and outcomes of fatal respiratory events after esophageal cancer surgery from 2011 through 2018: a nationwide cohort study in South Korea.
Pulmonary complications are common after esophageal cancer surgery, but information regarding fatal respiratory events, such as postoperative acute respiratory distress syndrome (ARDS) and respiratory failure, is lacking. We aimed to investigate the prevalence, risk factors, and outcomes of fatal respiratory events after esophageal cancer surgery. We performed a retrospective population-based cohort study based on data from the National Health Insurance Service database in South Korea. All adult patients diagnosed with esophageal cancer who underwent esophageal surgery between January 2011 and December 2018 were included. A total of 7039 patients were included in the final analysis. Among them, 100 patients (1.4%) experienced fatal respiratory adverse events (ARDS, 55 patients [0.8%]; respiratory failure, 45 patients [0.6%]). On multivariable logistic regression, residence in rural areas (vs. urban areas) at the time of surgery, open thoracotomy (vs. video-assisted thoracoscopic surgery), and lower annual case volume were associated with a higher prevalence of fatal respiratory adverse events. Moreover, postoperative fatal respiratory adverse events were related to increased in-hospital mortality, 1 year mortality, prolonged hospitalization, and increased total hospitalization costs. In South Korea, 1.4% of patients experienced fatal respiratory events (ARDS or respiratory failure) after esophageal cancer surgery. Some factors were revealed as risk factors for fatal respiratory events, and fatal respiratory events worsened clinical outcomes after esophageal cancer surgery.


The maternal diet index in pregnancy is associated with offspring allergic diseases: the Healthy Start study.
A systematic review showed limited associations between pregnancy diet and offspring allergy. We developed a maternal diet index during pregnancy that was associated with offspring allergy outcomes. Data came from Healthy Start, a Colorado pre-birth cohort of mother/offspring dyads. Food propensity questionnaires were completed during pregnancy. Offspring allergic rhinitis, atopic dermatitis, asthma, wheeze, and food allergy diagnosis up to age four were verified from electronic medical records. Data were randomized into test and replication sets. The index included the weighted combination of variables that best predicted a combined outcome of any allergy in the test set. Index utility was verified in the replication set. Separate adjusted and unadjusted logistic models estimated associations between the index and each offspring allergy diagnosis in the full sample. The index included weighted measures of intake of vegetables, yogurt, fried potatoes, rice/grains, red meats, pure fruit juice, and cold cereals. Vegetables and yogurt were associated with the prevention of any allergy, while other components were associated with increased disease. In adjusted models, a one-unit increase in the index was significantly associated with reduced odds of offspring allergic rhinitis (odds ratio (CI) 0.82 [0.72-0.94]), atopic dermatitis (0.77 [0.69-0.86]), asthma (0.84 [0.74-0.96]), and wheeze (0.80 [0.71-0.90]), but not food allergy (0.84 [0.66-1.08]). This is the first study that has shown associations between an index of maternal dietary intake during pregnancy and multiple offspring allergic diseases. The results give hope for prevention of allergic diseases in utero.