The prevalence of patients in a vegetative state and minimally conscious state in nursing homes in Austria.
To explore the epidemiology of patients in a Vegetative State (VS) and Minimally Conscious State (MCS) that are cared for in long-term care facilities in Austria. The study was inspired by increasing evidence that the cognitive abilities of minimal behavioural patients with disorders of consciousness may be under-rated. Since an unequivocal diagnostic code with which to follow-up these long-term patients after the acute event does not exist, a telephone survey was conducted. A three-step telephone- and questionnaire-based inquiry was conducted between 2007 and 2009. One hundred and fourteen out of 889 long-term care facilities and nursing homes cared for 269 patients in a VS and 120 patients in a MCS, indicating a prevalence of 3.36 patients per 100 000 for VS and 1.5 per 100 000 for MCS in long-term care facilities. The results are discussed in the light of differences in prevalence in other Western countries. Future studies should concentrate on these long-term patients since the results have implications regarding how to organize appropriate neurorehabilitative care that meets the needs of such patients.


Diversity of medicinal plants and their therapeutic usages of Kachin people (Jinghpaw) in the central part of Kachin State, Myanmar.
The traditional medical system plays a major role in healthcare in Kachin State, Myanmar, where long-term political instability persists and conventional healthcare facilities are inadequate. A knowledge of the traditional medicinal plants therefore benefits the Kachin people, yet documentation and records of the uses of these plants are rare. In this study, we attempt to answer the questions on what medicinal plants and how they are used by the Kachin people. We aimed to document knowledge of the traditional medicinal plants and to identify those most frequently used by the Kachin people. Eighty-two informants from eight villages in three townships were interviewed, and their knowledge of medicinal plants was recorded. The reported ailments were classified to the standard categories of the International Classification of Primary Care-2 (ICPC-2) system. Use reports (UR) were employed to evaluate the knowledge consensus of the informants. We recorded a total of 117 species used as medicinal plants, of which 22 are newly recorded medicinal plant species for Myanmar. The plants belonged to 103 genera in 52 families, and were used to treat a total of 72 ailments from 17 ICPC-2 disease categories. Fabaceae and Lamiaceae were the most highly represented families of medicinal plants, with eleven and eight species used, respectively. The most cited species based on URs were Tinospora cordifolia (Willd.) Hook.f. & Thomson (URs = 39), Oroxylum indicum (L.) Kurz (URs = 28), Aquilaria malaccensis Lam. (URs = 26), Chromolaena odorata (L.) R.M.King & H.Rob. (URs = 24), and Chloranthus elatior Link. (URs = 22). Digestive system disorder was the most prevalent disease category, and was treated with 47 different medicinal plants (URs = 142). Leaves were the most commonly used plant part; decoction was the dominant method of preparation; and oral consumption was the most frequent method of administration. Our study documented a list of 117 medicinal plants and their uses in traditional medicine based on the local knowledge of the Kachin people. The study also identified the five most frequently cited species and found that the plants investigated are used to treat a total of 72 diseases. The 642 therapeutic reports we collected showcase a rich and diverse living knowledge of medicinal plant use by the Kachin people. Moreover, we present 22 new medicinal records, enriching the list of known medicinal plants in Myanmar. This exploratory study has enabled us to assemble the local knowledge of the Kachin people into solid dataset that will allow further scientific validation and will potentially contribute to better integration of medicinal plants into the healthcare provision for Kachin people in Myanmar.


Assessment of coagulation profile by thromboelastometry in adult patients with cyanotic congenital heart disease.
Patients with cyanotic congenital heart disease (CCHD) have an increased risk of bleeding and thrombotic complications. Prolonged conventional coagulation screening parameters, such as activated partial thromboplastin time or prothrombin time, are reported in less than 20% of CCHD patients. The aim of this study was to determine the haemostatic abnormalities in 32 adult patients with CCHD by rotation thromboelastometry (ROTEM) with assessment of coagulation dynamic properties, as a guide for perioperative prophylaxis or haemostatic therapy. The control group consisted of 35 healthy subjects. Our results suggest that CCHD patients, in comparison to healthy controls, had a tendency to hypocoagulate with delayed activation of haemostasis and clot formation, initiated by both intrinsic and extrinsic activators. The growth of the clot was slower and the clot firmness was decreased, which may additionally contribute to bleeding diathesis. Moreover, the clot lysis readings suggest higher clot stability in the CCHD group. All velocity parameters were markedly lower in the CCHD patients, indicating a decreased rate of clot formation. Although coagulation tests and platelet count were normal, the usefulness of rotation thromboelastometry in monitoring or guiding therapy in CCHD patients is demonstrated. In conclusion, our results provide new insights into the data on hypocoagulation with impaired clot lysis in adult CCHD patients as determined by ROTEM. Our findings may assist in determining the optimal management of patients with CCHD undergoing surgery.


Targeted protein degraders march towards the clinic for neurodegenerative diseases.
Protein degraders are emerging as potent therapeutic tools to address neurological disorders and many complex diseases. It offered several key advantages, including the doses, drug resistance, and side effects over traditional occupancy-based inhibitors. Translation of chemical degraders into a clinical therapy for neurodegenerative disorders has a well-documented knowledge and resource gap. Researchers strive to develop clinical candidates employing chemical degraders' technologies, including hydrophobic tagging, molecular glues, proteolysis targeting chimeras (PROTACs), specific and nongenetic Inhibitor of Apoptosis Protein (IAP)-dependent protein erasers (SNIPERs), autophagy targeted chimeras, and autophagosome-tethered compounds for targeted degradation of pathological markers in neurodegenerative disease. Herein, we examined the present state of chemical-mediated targeted protein degradation in the quest for medications to treat neurodegenerative diseases. We further identified targeted degraders under clinical development for neurodegenerative diseases summarizing pertinent discoveries guiding the future of degradation therapeutics. We also addressed the necessary pharmacological interventions needed to achieve unprecedented therapeutic efficacy and its associated challenges.


Evaluation of a fast test to identify the presence of proline aminopeptidase in women with bacterial vaginosis.
The purpose of this study was to evaluate the activity of proline aminopeptidase by a rapid paper strip test in women with bacterial vaginosis (BV). Vaginal secretions of 1,387 voluntary patients attending the Obstetrics and Gynecology Infectious Diseases Clinic at Juárez Hospital of Mexico City were collected and examined. Patients were assigned into 2 groups: 483 with BV according to clinical and laboratory criteria and 604 without BV as the control group. For the purposes of this study, 300 patients with trichomonas and/or yeast were excluded from the BV group. The strips were prepared by using L-proline beta-naphthylamide and L-proline p-nitroanilide as the substrates to detect proline aminopeptidase activity in concentrated vaginal secretions. In parallel, all samples were also analyzed with the standard methods in microplates containing either sustrate as a control of the rapid strip test. The test was interpreted after 3-5 min of incubation. The results in the strip and microplate assays were similar in 95% of the samples. Sensitivity was 91.7% and specificity was 94.2%; probability of BV if the test is positive was 92.6% and negative predictive value was 93.4%. These findings indicate that this aminopeptidase rapid strip assay provides a 3-5 min identification of activity of the enzyme in women with BV. The procedure is a rapid, non-expensive, sensitive, and useful test at the gynecologic clinic.


Stem cells to tissue: molecular, cellular and anatomical heterogeneity in skeletal muscle.
Multiple waves of muscle precursors are released from skeletal muscle progenitor cells throughout developmental life, and this process is initiated in precise locations in the embryo. Skeletal muscle diversifies not only after the acquisition of muscle identity, but curiously heterogeneity is observed even in the stem cell population. Recent studies on cell lineage, cell fusion and the nature of post-natal satellite cells have expanded on our fundamental knowledge of the formation of this tissue, and how this tissue is replenished by resident and circulating regenerative stem cells during adult life.


Selective sentinel lymphadenectomy for malignant melanoma, Merkel cell carcinoma, and squamous cell carcinoma.
To date, selective sentinel lymphadenectomy (SSL) should be considered a standard approach for staging patients with primary invasive melanoma greater than or equal to 1 mm. It is imperative that the multidisciplinary team master the techniques of preoperative lymphoscintigraphy, intraoperative lymphatic mapping, and postoperative pathologic evaluation of the sentinel lymph nodes (SLNs). An SLN is defined as a blue, "hot" and any subsequent lymph node greater than 10% of the ex vivo count of the hottest lymph node. Any enlarged or indurated lymph node in the nodal basin should be excised. Frozen sections are not recommended. For extremity melanoma, delayed SSL may be performed. Preoperative lymphoscintigraphy for extremity melanoma may be done the night before so that the surgery can be scheduled as the first case of the following day. Every surgeon who uses blue dye should be aware of the potential adverse reaction to isosulfan blue and treatment for such a potential fatal reaction. A complete lymph node dissection is done if the SLN is found to be positive. Elective lymph node dissection (ELND) should not be done if an SSL can be performed as a staging procedure. SSL has further been applied to stage the nodal basin for Merkel cell carcinoma and high-risk squamous cell carcinoma. It is important for investigators involved with the SSL to follow the clinical outcome of these patients, so that the role of SSL can be further defined.


Breast cancer and depot-medroxyprogesterone acetate: a multinational study. WHO Collaborative Study of Neoplasia and Steroid Contraceptives.
To determine whether the long-acting injectable progestational contraceptive DMPA, depot-medroxyprogesterone acetate, alters the risk of breast cancer in women, a hospital-based case-control study was conducted in five participating hospitals in Nairobi, Kenya, Mexico City, Mexico, Bangkok, Thailand (two hospitals), and Chiang Mai, Thailand. 869 women with newly diagnosed breast cancer who were young enough to have used DMPA for contraception, and 11,890 women of similar age who had been admitted to hospital for conditions unrelated to steroid contraceptive use, were interviewed to obtain information about previous use of steroid contraceptives and suspected risk factors for breast cancer. DMPA had been used by 12.5% of cases and 12.2% of controls. Relative risk (95% Cl) in women who had ever used DMPA was 1.21 (0.96, 1.52). Risk was increased within the first 4 years of initial exposure, mainly in women under 35 years. This observation did not seem to result from selective surveillance for breast cancer in DMPA users. Risk did not increase with duration of use, and was not increased in women who had started to use DMPA more than 5 years previously. These results provide reassurance that women who have used DMPA for a long time and who initiated use many years previously are not at increased risk of breast cancer.


Nasal Injuries in Sports.
Nasal trauma is a common consequence of athletic competition. The nasal bones are the most commonly fractured facial bone and are particularly at risk during sports participation. Acute management of trauma to the nose includes thorough evaluation of all injuries and may require immediate management for repair of facial lacerations, epistaxis control, or septal hematoma drainage. Nasal fractures can often be addressed with closed reduction techniques; however, in the setting of complex nasal trauma, an open approach may be indicated. Using appropriate treatment techniques, posttraumatic nasal sequelae can be minimized; most patients report satisfactory long-term nasal form and function.


Polyfunctional, Proinflammatory, Tissue-Resident Memory Phenotype and Function of Synovial Interleukin-17A+CD8+ T Cells in Psoriatic Arthritis.
Genetic associations imply a role for CD8+ T cells and the interleukin-23 (IL-23)/IL-17 axis in psoriatic arthritis (PsA) and other spondyloarthritides (SpA). IL-17A+CD8+ (Tc17) T cells are enriched in the synovial fluid (SF) of patients with PsA, and IL-17A blockade is clinically efficacious in PsA/SpA. This study was undertaken to determine the immunophenotype, molecular profile, and function of synovial Tc17 cells in order to elucidate their role in PsA/SpA pathogenesis. Peripheral blood (PB) and SF mononuclear cells were isolated from patients with PsA or other types of SpA. Cells were phenotypically, transcriptionally, and functionally analyzed by flow cytometry (n = 6-18), T cell receptor β (TCRβ) sequencing (n = 3), RNA-Seq (n = 3), quantitative reverse transcriptase-polymerase chain reaction (n = 4), and Luminex or enzyme-linked immunosorbent assay (n = 4-16). IL-17A+CD8+ T cells were predominantly TCRαβ+ and their frequencies were increased in the SF versus the PB of patients with established PsA (P < 0.0001) or other SpA (P = 0.0009). TCRβ sequencing showed that these cells were polyclonal in PsA (median clonality 0.08), while RNA-Seq and deep immunophenotyping revealed that PsA synovial Tc17 cells had hallmarks of Th17 cells (RORC/IL23R/CCR6/CD161) and Tc1 cells (granzyme A/B). Synovial Tc17 cells showed a strong tissue-resident memory T (Trm) cell signature and secreted a range of proinflammatory cytokines. We identified CXCR6 as a marker for synovial Tc17 cells, and increased levels of CXCR6 ligand CXCL16 in PsA SF (P = 0.0005), which may contribute to their retention in the joint. Our results identify synovial Tc17 cells as a polyclonal subset of Trm cells characterized by polyfunctional, proinflammatory mediator production and CXCR6 expression. The molecular signature and functional profiling of these cells may help explain how Tc17 cells can contribute to synovial inflammation and disease persistence in PsA and possibly other types of SpA.


Right atrial structural remodeling predict worse outcomes in transcatheter mitral valve repair.
In the current study, we assess the predictive role of right and left atrial volume indices (RAVI and LAVI) as well as the ratio of RAVI/LAVI (RLR) on mortality following transcatheter mitral valve repair (TMVr). Transthoracic echocardiograms of 158 patients who underwent TMVr at a single academic medical center from 2011 to 2018 were reviewed retrospectively. RAVI and LAVI were calculated using Simpson's method. Patients were stratified based on etiology of mitral regurgitation (MR). Cox proportional-hazard regression was created utilizing MR type, STS-score, and RLR to assess the independent association of RLR with survival. Kaplan-Meier analysis was used to analyze the association between RAVI and LAVI with all-cause mortality. Hemodynamic values from preprocedural right heart catheterization were also compared between RLR groups. Among 123 patients included (median age 81.3 years; 52.5% female) there were 50 deaths during median follow-up of 3.0 years. Patients with a high RAVI and low LAVI had significantly higher all-cause mortality while patients with high LAVI and low RAVI had significantly improved all-cause mortality compared to other groups (p = 0.0032). RLR was significantly associated with mortality in patients with both functional and degenerative MR (p = 0.0038). Finally, Cox proportion-hazard modeling demonstrated that an elevated RLR above the median value was an independent predictor of all-cause mortality [HR = 2.304; 95% CI = 1.26-4.21, p = 0.006] when MR type and STS score were accounted for. Patients with a high RAVI and low LAVI had significantly increased mortality than other groups following TMVr suggesting RA remodeling may predict worse outcomes following the procedure. Concordantly, RLR was predictive of mortality independent of MR type and preprocedural STS-score. These indices may provide additional risk stratification in patients undergoing evaluation for TMVr.


Hemodynamic effects of blood volume restitution following a hemorrhage in rats with portal hypertension due to cirrhosis of the liver: influence of the extent of portal-systemic shunting.
The present study investigated whether, in rats with portal hypertension due to cirrhosis of the liver induced by carbon tetrachloride, blood volume restitution following a hemorrhage produces an increase of portal pressure beyond control values, as observed in rats with prehepatic portal hypertension. Since carbon tetrachloride-induced cirrhosis caused mild portal-systemic shunting, in some of the cirrhotic rats (12 of 29 rats) portal-systemic shunting was enhanced by a transient (4 days) partial constriction of the portal vein, which was removed 1 week prior to the study. After baseline measurements of portal pressure and arterial pressure, 15 ml per kg of blood were withdrawn at a rate of 0.3 ml per min and reinfused 15 min later. After blood reinfusion, portal pressure and arterial pressure were measured again, and cardiac output, regional blood flows and portal-systemic shunting were determined using radioactive microspheres. Portal-systemic shunting was 78 +/- 11% of total blood flow in the cirrhotic rats that had temporary portal vein constriction, but only 5 +/- 2% (p less than 0.001) in those that did not. Blood volume restitution in low-portal-systemic shunting rats did not produce any significant modification in splanchnic or systemic hemodynamics. However, in rats with high portal-systemic shunting, blood volume restitution produced a significant increase in portal pressure (from 9.9 +/- 0.9 to 13.5 +/- 0.9 mmHg, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)


Subunit interactions of skeletal muscle myosin and myosin subfragment 1. Evidence for heavy chain-alkali light chain association-dissociation equilibrium.
Modification of the free alkali light chains of myosin by iodoacetylation results in a much lower extent of exchange into myosin subfragment 1 by the thermal hybridization procedure (Burke, M., and Sivaramakrishnan, M. (1981) Biochemistry 20, 5908-5913). As reported by others (Wagner, P. D., and Stone, D. B. (1983) J. Biol. Chem. 258, 8876-8882), free alkali light chains modified by iodoacetate at their single sulfhydryl residue exhibit minimal exchange into intact myosin. However, when unmodified alkali light chain is used to probe for exchange, close to the theoretical limit of exchange is observed for subfragment 1, and significant levels of exchange are found for myosin. It appears that modification of the free alkali light chain alters the structure of the protein, and this causes either a marked reduction in its affinity for the heavy chain or in its ability to enter the light chain binding site. This conclusion is supported by tryptic digestions done on the unmodified and modified free light chains where it is found that the latter is degraded at a much faster rate, indicating a more open structure for the modified protein. The observation that alkali light chain exchanges into myosin when unmodified alkali light chains are used indicates that the presence of the associated 5,5'-dithiobis-(2-nitrobenzoic acid) light chains does not preclude the reversible dissociation of this subunit from myosin under ionic and temperature conditions approaching the physiological state.


Radionuclide scintiphotography in defining postoperative pulmonary vasoconstriction. Succesful results after tolazoline administration in a four-month-old infant with congenital heart disease.
99mTechnetium macroaggregated albumin has successfully been used to define severe postoperative pulmonary vasoconstriction in a four-month-old boy with D-transposition of the great vessels who had undergone a Blalock-Hanlon surgical atrial septectomy. Radionuclide imaging documented clinically suspected pulmonary vasoconstriction and led to the successful use of tolazoline (Priscoline) to reverse the vasoconstriction with improved pulmonary blood flow patterns.


Nanomechanics of negatively supercoiled diaminopurine-substituted DNA.
Single molecule experiments have demonstrated a progressive transition from a B- to an L-form helix as DNA is gently stretched and progressively unwound. The particular sequence of a DNA segment defines both base stacking and hydrogen bonding that affect the partitioning and conformations of the two phases. Naturally or artificially modified bases alter H-bonds and base stacking and DNA with diaminopurine (DAP) replacing adenine was synthesized to produce linear fragments with triply hydrogen-bonded DAP:T base pairs. Both unmodified and DAP-substituted DNA transitioned from a B- to an L-helix under physiological conditions of mild tension and unwinding. This transition avoids writhing and the ease of this transition may prevent cumbersome topological rearrangements in genomic DNA that would require topoisomerase activity to resolve. L-DNA displayed about tenfold lower persistence length than B-DNA. However, left-handed DAP-substituted DNA was twice as stiff as unmodified L-DNA. Unmodified DNA and DAP-substituted DNA have very distinct mechanical characteristics at physiological levels of negative supercoiling and tension.


Rapid and simple method for the simultaneous determination of 3,4-dihydroxyphenylacetic acid, 5-hydroxyindole-3-acetic acid and 4-hydroxy-3-methoxyphenylacetic acid in human plasma by high-performance liquid chromatography with electrochemical detection.
A simple procedure for the simultaneous determination of major metabolites of dopamine and serotonin in plasma, i.e. 3,4-dihydroxyphenylacetic acid, 5-hydroxyindole-3-acetic acid, and 4-hydroxy-3-methoxyphenylacetic acid, was developed. The method is based on rapid isolation of the compounds by one-step clean-up on a small C18 column, followed by high-performance liquid chromatography with dual electrochemical detection. The system is readily used for clinical applications.


Reflux patterns in patients with achalasia without operation.
Five patients with achalasia who had not had an operation underwent esophageal manometry and 24-hour, ambulatory pH monitoring to determine the pattern and extent of esophageal reflux. One patient had reflux within normal limits. In 2 patients, reflux occurred 0.5% of the total time and no episodes of supine reflux were recorded. In the 2 remaining patients, reflux was measured 16.8% and 55.3% of the total time; however, in both patients, these results were influenced by lengthy bouts of supine reflux. These indices of reflux were not influenced by differences in resting lower esophageal sphincter tone, position, or length. Twenty-four-hour esophageal pH monitoring can be useful in the preoperative assessment of patients with achalasia, and the information obtained might influence the choice of operative procedure.


Novel Probiotic Lactic Acid Bacteria with In Vitro Bioremediation Potential of Toxic Lead and Cadmium.
In this study, newly isolated lactic acid bacteria (LAB) were screened for the potential bioremediation capacity against toxic lead (Pb, II) and cadmium (Cd, II) with their bioaccessibility and survivability. Five strains were selected from eighteen previously isolated probiotic LAB strains based on heavy metal-resistant potentiality through in vitro disc-diffusion assay. These five strains were evaluated in vitro to explore the Pb and Cd binding and removal efficiencies using Flame Atomic Absorption Spectrophotometry. At the same time, their bioaccessibility and survivability were assessed in a dynamic in vitro gastrointestinal digestion model. The results revealed that all the tested strains were shown to have a high magnitude of minimum inhibitory concentration values ranging from 500 to 2000 mg/L with 5 to 25 mm growth inhibition zones. The results also demonstrated a significant (P < 0.05) removal of Pb and Cd among five tested LAB strains. Lactobacillus delbrueckii subsp. bulgaricus LDMB02 showed the highest removal rates of Pb and Cd. It was also revealed that these strains significantly reduced Pb and Cd bioaccessibility from 42 to 50% and 40 to 58%, respectively. Moreover, these strains were shown to have significant survivability against Pb and Cd, ranging from 80.1 to 85.4% and 81.5 to 87.5%, respectively. This study recommends the immense potential exploit of LAB as a probiotic to protect human health from the adverse effects of Pb and Cd toxicity.


Interdisciplinary advances reshape the delivery tools for effective NASH treatment.
Nonalcoholic steatohepatitis (NASH), a severe systemic and inflammatory subtype of nonsalcoholic fatty liver disease, eventually develops into cirrhosis and hepatocellular carcinoma with few options for effective treatment. Currently potent small molecules identified in preclinical studies are confronted with adverse effects and long-term ineffectiveness in clinical trials. Nevertheless, highly specific delivery tools designed from interdisciplinary concepts may address the significant challenges by either effectively increasing the concentrations of drugs in target cell types, or selectively manipulating the gene expression in liver to resolve NASH. We focus on dissecting the detailed principles of the latest interdisciplinary advances and concepts that direct the design of future delivery tools to enhance the efficacy. Recent advances have indicated that cell and organelle-specific vehicles, non-coding RNA research (e.g. saRNA, hybrid miRNA) improve the specificity, while small extracellular vesicles and coacervates increase the cellular uptake of therapeutics. Moreover, strategies based on interdisciplinary advances drastically elevate drug loading capacity and delivery efficiency and ameliorate NASH and other liver diseases. The latest concepts and advances in chemistry, biochemistry and machine learning technology provide the framework and strategies for the design of more effective tools to treat NASH, other pivotal liver diseases and metabolic disorders.


ABV-CoViD: An Ensemble Forecasting Model to Predict Availability of Beds and Ventilators for COVID-19 Like Pandemics.
Recently, healthcare stakeholders have orchestrated steps to strengthen and curb the COVID-19 wave. There has been a surge in vaccinations to curb the virus wave, but it is crucial to strengthen our healthcare resources to fight COVID-19 and like pandemics. Recent researchers have suggested effective forecasting models for COVID-19 transmission rate, spread, and the number of positive cases, but the focus on healthcare resources to meet the current spread is not discussed. Motivated from the gap, in this paper, we propose a scheme, ABV-CoViD (Availibility of Beds and Ventilators for COVID-19 patients), that forms an ensemble forecasting model to predict the availability of beds and ventilators (ABV) for the COVID-19 patients. The scheme considers a region-wise demarcation for the allotment of beds and ventilators (BV), termed resources, based on region-wise ABV and COVID-19 positive patients (inside the hospitals occupying the BV resource). We consider an integration of artificial neural network (ANN) and auto-regressive integrated neural network (ARIMA) model to address both the linear and non-linear dependencies. We also consider the effective wave spread of COVID-19 on external patients (not occupying the BV resources) through a [Formula: see text]- ARNN model, which gives us long-term complex dependencies of BV resources in the future time window. We have considered the COVID-19 healthcare dataset on 3 USA regions (Illinois, Michigan, and Indiana) for testing our ensemble forecasting scheme from January 2021 to May 2022. We evaluated our scheme in terms of statistical performance metrics and validated that ensemble methods have higher accuracy. In simulation, for linear modelling, we considered the [Formula: see text] model, and [Formula: see text] model for ANN modelling. We considered the [Formula: see text](12,6) forecasting. On a population of 2,93,90,897, the obtained mean absolute error (MAE) on average for 3 regions is 170.5514. The average root means square error (RMSE) of [Formula: see text]-ARNN is 333.18, with an accuracy of 98.876%, which shows the scheme's efficacy in ABV measurement over conventional and manual resource allocation schemes.


Impact of needle type on substitution volume during online hemodiafiltration: plastic cannulae versus metal needles.
Plastic cannulae have attracted increasing interest as an alternative to traditional metal needles with the aim of reducing cannulation-related complications. We investigated whether the substitution volumes during hemodiafiltration differ using these two types of needles in dialysis patients. An intervention study involving 26 hemodialysis patients was conducted in Korea between March and September in 2021. Patients first received online hemodiafiltration using traditional metal needles, and thereafter plastic cannulae were used in a stepwise protocol. Repeated-measures design and linear mixed-effect models were used to compare substitution volumes between the two needle types with the same inner diameter. The mean patient age was 62.7 years, and their mean dialysis vintage was 95.2 months. Most patients (92.3%) had an arteriovenous fistula as the vascular access. The substitution volume increased as blood flow and needle size increased for both plastic cannulae and metal needles. The substitution volume was significantly higher with 17-gauge (G) plastic cannulae than with 16-G metal needles at blood flow rates of 280, 300, and 330 mL/min. Similar results were obtained for 15-G metal needles and 16-G plastic cannulae at a blood flow rate of 330 mL/min. However, the patient ratings of pain on a visual analogue scale were higher for plastic cannulae. Higher substitution volumes were obtained at the same prescribed blood flow rate with plastic cannulae than with metal needles during online hemodiafiltration. Plastic cannulae are an option for achieving high-volume hemodiafiltration for patients with low blood flow rates.


Prospective associations between cannabis use and depressive symptoms across adolescence and early adulthood.
Cannabis use and occurrences of depression during adolescence are common. However, the temporal relationship between the two is less understood. Does depression lead to cannabis use, or does cannabis use lead to depression, or is it a combination of both? Furthermore, this directionality is confounded by other substance use, specifically binge drinking, which is common during adolescence. This study aimed to examine the temporal directionality of cannabis use and depression among a prospective, longitudinal, sequential cohort of 15 to 24-year-olds. Data were drawn from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study. The final sample included 767 participants. Multilevel regression models were run to assess concurrent (at the same time point) and prospective (1 year later) associations between cannabis use and depression. When measured concurrently, depressive symptoms did not significantly predict past-month cannabis use but did significantly predict more days of use among cannabis users. Prospective associations indicated that depressive symptoms significantly predicted cannabis use 1 year later and cannabis use significantly predicted depressive symptoms 1 year later. We found no evidence that these associations varied by age or binge drinking. Overall, the relationship between cannabis use and depression appears to be complex and not unidirectional.


Effects of dietary phytoestrogen exposure during perinatal period.
Developmental effects of phytoestrogens were studied in offspring from pregnant rats who received a free-feeding diet of either rat chow that was very low in phytoestrogens (low phyto), rat chow low in phytoestrogens and given a genistein and diadzein supplement tablet (high phyto), or normal rat chow (normal) from the second week of pregnancy to weaning (postnatal day 21). Measurements of anogenital distance, daily weights, righting reflex and ultrasonic vocalizations were made on neonatal pups and plasma testosterone and corticosterone were assessed in adult males. There was a significant effect of phytoestrogen treatment on USV for all male and female offspring. Differences between groups in daily weights and anogenital distance were attributed to the micronutrient levels of the two rat chow types employed in this study. No differences in righting reflex test, corticosterone levels or testosterone levels were found among treatment conditions. These results are the first demonstration of phytoestrogens affecting USVs and underscore the complexity of the effects of these substances on biobehavioral development.


Leucine-rich glioma-inactivated protein 1 antibody-associated encephalitis in a 22-month-old girl: a case report.
LGI-1 antibody-associated encephalitis is a type of autoimmune encephalitis with a lower prevalence than NMDAR antibody-associated encephalitis. LGI-1 antibody-associated encephalitis is the second most prevalent of all autoimmune encephalitides. LGI-1 antibodies interfere with the interactions of inter-synaptic proteins to produce clinical manifestations (N Engl J Med 378:840-851, 2018). Leucine-rich glioma-inactivated protein 1 (LGI-1) antibody-associated encephalitis is a subtype of autoimmune encephalitis with a low incidence. We report a case of a girl aged 22 months with convulsive seizures, psycho-behavioral abnormalities, sleep disorders, and limb tremors. This patient was diagnosed with LGI-1 antibody-associated encephalitis based on electroencephalography (EEG) examinations and autoimmune encephalitis antibody analyses. A combined therapy of anti-epileptic and immunosuppressant drugs was effective in controlling the patient's neurological symptoms. The incidence of LGI-1 antibody-associated encephalitis is low and it occurs mostly in middle-aged and elderly patients, although it occasionally occurs in pediatric patients. To the best of our knowledge, this report describes the youngest patient with LGI-1 antibody-associated encephalitis. Following timely diagnosis, administration of anti-epileptic and immunosuppressant therapy was remarkably effective.


Basal, cAMP- and cGMP-dependent protein kinases in human brain tumors.
Since the effects of cyclic nucleotides are mediated via protein kinases activation, we have studied the properties and regulation of these enzymes in cytosol and particulate fraction of normal cerebral tissues and of some human brain tumors. We found that distribution and activity of cyclic nucleotide-dependent protein kinases are regulated differently among various brain tumors and in comparison to normal gray and white matter. Pathological tissues show an higher cGMP-dependent protein kinase and this biochemical pattern is particularly evident in tumors with more pronounced malignancy. These data further confirm the hypothesis of a correlation between the increase of cGMP function and cellular growth and malignancy.


Inhibition of cyclooxygenase-2 by NS398 attenuates noise-induced hearing loss in mice.
Noise-induced hearing loss (NIHL) is an important occupational disorder. However, the molecular mechanisms underlying NIHL have not been fully clarified; therefore, the condition lacks effective therapeutic methods. Cyclooxygenase-2 (Cox-2) is an inducible enzyme involved in the synthesis of prostaglandins, and has been implicated in many pathophysiological events, such as oxidative stress and inflammation. In this study, we investigated the possible role of Cox-2 in the mechanisms of NIHL and the therapeutic effect of the Cox-2 inhibitor NS398 on NIHL using a mouse model. We demonstrated that Cox-2 is constitutively expressed in the mouse cochlea, and its expression could be dramatically up-regulated by high levels of noise exposure. Furthermore, we demonstrated that pre-treatment with the Cox-2 inhibitor NS398 could inhibit Cox-2 expression during noise overstimulation; and could attenuate noise-induced hearing loss and hair cell damage. Our results suggest that Cox-2 is involved in the pathogenesis of NIHL; and pharmacological inhibition of Cox-2 has considerable therapeutic potential in NIHL.


Resistance screening and in silico characterization of cloned novel RGA from multi-race resistant lentil germplasm against Fusarium wilt (Fusarium oxysporum f. sp. lentis).
Fusarium wilt caused by Fusarium oxysporum f. sp. lentis (Fol) is the most devastating disease of lentil present worldwide. Identification of multi-race fusarium wilt resistance genes and their incorporation into existing cultivars will help to reduce yield losses. In the present study, 100 lentil germplasms belonging to seven lentil species were screened against seven prevalent races of Fol, and accessions IC201561 (Lens culinaris subsp. culinaris), EC714243 (L. c. subsp. odemensis), and EC718238 (L. nigricans) were identified as resistant. The typical R gene codes for the nucleotide-binding site and leucine-rich repeats (NBS-LRR) at the C terminal are linked to either the Toll/interleukin 1-like receptor (TIR) or coiled coil (CC) at the N terminal. In the present study, degenerate primers, designed from the NBS region amplifying the P-loop to the GLPLA motif, isolated forty-five resistance gene analogues (RGAs) from identified resistant accessions. The sequence alignment identified both classes of RGAs, TIR and non-TIR, based on the presence of aspartate (D) and tryptophan (W) at the end of the kinase motif, respectively. The phylogenetic analysis grouped the RGAs into six classes, from LRGA1 to LRGA6, which determined the diversity of the RGAs present in the host. Grouping of the RGAs identified from Lens nigricans, LnRGA 2, 9, 13 with I2 revealed the structural similarity with the fusarium resistance gene. The similarity index ranged from 27.85% to 86.98% among the RGAs and from 26.83% to 49.41% among the known R genes, I2, Gpa2, M, and L6. The active binding sites present along the conserved motifs grouped the RGAs into 13 groups. ADP/ATP, being the potential ligand, determines the ATP binding and ATP hydrolysis activity of the RGAs. The isolated RGAs can be used to develop markers linked to the functional R gene. Furthermore, expression analysis and full-length gene isolation pave the path to identifying the molecular mechanism involved in resistance.


Mismatch negativity (MMN) is altered by directing attention.
MMN is a negative component resulting from the difference in event-related potential (ERP) waveforms elicited by a standard and a deviant stimulus. It is usually studied in the absence of attentional requirements. We compared this measure of perceptual comparison in a non-task situation (three tones presented) with that obtained in a task requiring focused attention and response to the third tone. MMN (comparison of standard and deviant irrelevant tones) increased with focused attention to the third (target) tone and frontal maxima shifted slightly posteriorly. The succeeding P3 in the difference waveform increased more posteriorly than frontally confirming continued differential processing of irrelevant stimuli under active conditions. This demonstrates that not only attending to stimuli, but the active processing of irrelevant stimuli (vs passive perception) involves small changes in the amount and distribution of neural activity.


Do alcohol expectancies become intoxicated outcomes? A test of social-learning theory in a naturalistic bar setting.
According to social-learning theory, alcohol outcome expectancies (AOEs) are important motivators of drinking behavior that are reinforced, in part, as a result of one's direct experience with alcohol's intoxicating effects. To date, limited research has been conducted in naturalistic bar settings to examine the congruency between AOEs held prior to drinking and individuals' subjective perceptions of post-drinking outcomes. The present study was designed to fill this void. Fifty regular bar patrons (30 males and 20 females) participated. Prior to the initiation of the drinking episode, expected alcohol effects and associated valences were assessed using the Comprehensive Effects of Alcohol (CEOA) questionnaire [Fromme, Stroot, and Kaplan, (1993) 19]. At the conclusion of the drinking episode, all individuals completed the CEOA that was modified in order to assess their subjective alcohol-related outcomes. Overall, while individuals' intoxicated outcomes generally mirrored their pre-drinking AOEs, a lack of congruency was observed with respect to alcohol-related risk and aggression, such that participants reported feeling less aggressive and more disinclined to engage in risky behavior than they had expected as a result of consuming alcohol. As well, two presumably negative (i.e., behavioral impairment and self-perception) and one positive (i.e., liquid courage) alcohol-related outcomes were rated more favorably at the end of the drinking episode. Finally, a main effect for gender was found for specific AOEs. The implications of these findings for social-learning explanations of drinking behavior are discussed.


Phosphaturic mesenchymal tumor: Case report.
Phosphaturic mesenchymal tumors (PMT) are an extremely rare pathologic phenomenon that presents as paraneoplastic tumor-induced osteomalacia. Their diagnosis is often significantly delayed due to their rare occurrence in addition to the generalized and vague symptoms of their presentation including progressive bone pain, myopathies, arthralgias, fractures, and generalized weakness. This case report identifies a very characteristic presentation of a 37-year old African American male suffering from a PMT; with symptom onset presenting over 5-years prior to presentation with a consistent complaint of progressive and debilitating quadriparesis. The tumor was first identified by pelvic computerized tomography, although it was initially thought to be a noncontributory benign soft tissue mass. It was only after being hospitalized due to a severe and unresponsive hypophosphatemic state (less than 1 mg/dl) that the collective differential switched to one of a PMT with follow up nuclear 99mTc bone scintigraphy and magnetic resonance imaging being used to aid in the overall assessment of changes, extent, and general metabolic properties of the tumor. The confirmatory diagnosis of a PMT was later established through both serum fibroblast growth factor 23 testing and histopathologic review of the surgically removed specimen. By including this rare but curative disease into the differential of osteomalacia and thereby further examining patient serum phosphate levels, the previous 5-7 year delay in diagnosis will be dramatically reduced.


[Giant fetal ovarian cyst. Diagnosis and treatment].
A case of a prenatally diagnosed fetal ovarian cyst is presented. The pregnancy was uneventful and the girl delivered by cesarean because of the size of the cyst. The cyst was removed by laparotomy on the day of the delivery and luteum ovarian cyst was the histologic diagnosis.


Dynamic coronary obstruction as a cause of angina pectoris: implications regarding therapy.
The strong link demonstrated at autopsy between coronary atherosclerosis and angina pectoris led to the important concept that a fixed obstruction of 1 or more coronary arteries was the pathophysiologic cause of angina: myocardial ischemia and angina occurred when myocardial oxygen demand out-stripped the capacity of the diseased coronary artery to deliver oxygen. Therapeutic strategies were based on attempts to lower myocardial oxygen needs induced by physical and emotional stress. However, the finding that dynamic increases in coronary vascular resistance can also either precipitate ischemia or reduce the threshold of myocardial oxygen consumption (MVO2) at which it occurs has profoundly altered our understanding of the pathophysiologic features of angina and, therefore, its treatment. Dynamic coronary obstruction can occur at the large-vessel level, causing Prinzmetal's or variant angina. It is also possible that in some patients a continuum of large-vessel coronary vasoconstrictor tone exists, causing the common clinical situation manifested by angina with variable thresholds of onset. Recent studies have demonstrated that increases in the resistance offered to flow by small coronary arteries too small to be imaged by angiography can also decrease anginal threshold. The fact that ischemia can be precipitated by dynamic increases in large- or small-vessel coronary resistance has important implications for the therapy of angina pectoris. In those persons who mostly have a dynamic component contributing to their coronary obstruction, primary intervention with vasodilator therapy, including nitrates and calcium-channel blocking agents, are probably most effective therapeutically.(ABSTRACT TRUNCATED AT 250 WORDS)


The Effect of Vibration Treatments Combined with Teriparatide or Strontium Ranelate on Bone Healing and Muscle in Ovariectomized Rats.
The aim of the present study was to study the effect of combined therapy of teriparatide (PTH) or strontium ranelate (SR) with whole-body vibration (WBV) on bone healing and muscle properties in an osteopenic rat model. Seventy-two rats (3 months old) were bilaterally ovariectomized (Ovx), and 12 rats were left intact (Non-Ovx). After 8 weeks, bilateral transverse osteotomy was performed at the tibia metaphysis in all rats. Thereafter, Ovx rats were divided into six groups (n = 12): (1) Ovx-no treatment, (2) Ovx + vibration (Vib), (3) SR, (4) SR + Vib, (5) PTH, and (6) PTH + Vib. PTH (40 μg/kg BW sc. 5×/week) and SR (613 mg/kg BW in food daily) were applied on the day of ovariectomy, vibration treatments 5 days later (vertical, 70 Hz, 0.5 mm, 2×/day for 15 min) for up to 6 weeks. In the WBV + SR group, the callus density, trabecular number, and Alp and Oc gene expression were decreased compared to SR alone. In the WBV + PTH group, the cortical and callus widths, biomechanical properties, Opg gene expression, and Opg/Rankl ratio were increased; the cortical and callus densities were decreased compared to PTH alone. A case of non-bridging was found in both vibrated groups. Vibration alone did not change the bone parameters; PTH possessed a stronger effect than SR therapy. In muscles, combined therapies improved the fiber size of Ovx rats. WBV could be applied alone or in combination with anti-osteoporosis drug therapy to improve muscle tissue. However, in patients with fractures, anti-osteoporosis treatments and the application of vibration could have an adverse effect on bone healing.


Lipoprotein profile in long term theophylline administration in children with asthma.
Atherosclerosis in childhood has a slowly progressive course and its clinical features usually become prominent in middle ages. Hypercholesterolemia is one of the major risk factors for the development of atherosclerosis. A clear correlation exists between hypercholesterolemia in childhood and atherosclerotic lesions extending into adulthood.In this study, we evaluated the effect of slow release theophylline (SRT) treatment on plasma lipid profile and assessed the risk for atherosclerotic coronary heart disease in children with bronchial asthma. Group 1 consisted of 15 children with a mean age of 10.8 3.19 years who received SRT for bronchial asthma for a mean period of 9.13 2.17 months. Group 2 was composed of 15 children with a mean age of 11.40 3.78 years and followed up for bronchial asthma, who received no SRT treatment. Group 3 comprised 15 children with a mean age of 9.00 3.76 years and no history of asthma or wheezing. In all patients lipid profiles were assessed by measuring levels of plasma triglyceride, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) apolipoprotein A (Apo-A) and apolipoprotein B (Apo-B). In group 1, the mean total cholesterol level was 175.53 24.36 mg/dl, LDL-C level was 91.00 24.07 mg/dl and Apo-B level was 87.27 12.74 mg/dl after SRT treatment. In group 1, group 2 (control group with asthma) and group 3 (the non-asthmatic control group), the mean plasma lipid level after SRT treatment was significantly higher than that before SRT treatment. In conclusion, long-term SRT treatment in children with bronchial asthma may alter lipid profile and may increase the risk for developing atherosclerotic coronary heart disease.


Comparison of the efficacy and safety of single-agent and doublet chemotherapy in advanced non-small cell lung cancer in the elderly: a meta-analysis.
In patients with advanced non-small cell lung cancer (NSCLC) aged more than 70 years, the benefit-to-risk ratio of doublet chemotherapy vs single-agent is not established. We performed a meta-analysis (MA), with a PubMed query using keywords simultaneously (Randomized controlled trial, Aged, Anti-neoplastic combined chemotherapy protocols/therapeutic use, Carcinoma, Non-small cell lung/drug therapy). Abstracts from ASCO, WCLC, and ESMO proceedings were reviewed. Articles were also obtained by cross-checking references. Third-generation agents (gemcitabine, vinorelbine, paclitaxel, docetaxel) in combination with or without platinum were included. The efficacy outcomes were Overall Response Rate (ORR) and 1-Year Overall Survival (OS). We used EasyMA software and a random-effect model in case of heterogeneity. This MA comprised 10 studies including 2605 patients (mean age 74; 1866 men and 620 women; 654 stage IIIB and 1677 stage IV; 839 squamous cell cancers, 968 adenocarcinomas, 521 other pathological types). One-year OS (including the last trial by Abe) did not significantly improve for doublets compared with single-agents (HR 0.92; 95% Confidence Interval or CI: 0.82-1.03) whereas it improved significantly before inclusion of this last study, when the study by Quoix et al., the most favorable to doublets, was included. However, doublet chemotherapy significantly improved ORR after inclusion of Abe study (HR 1.51; 1.22-1.86; p<0.001). OS was not significantly improved, neither by doublets including platinum (HR 0.90, 0.70-1.16), nor by those without platinum (HR 0.94, 0.84-1.07). ORR, but not OS, was improved by doublets including a taxane (docetaxel and paclitaxel) (HR 1.72; 1.28-2.33) except for paclitaxel with a significant OS and ORR benefit. All-grade neutropenia thrombocytopenia and anemia were significantly more frequent with doublets than with single-agents (HR 1.26, 1.15-1.39; 1.75, 1.11-2.77 and 1.33, 1.17-1.52 respectively). Grade 3/4 thrombocytopenia and anemia but not neutropenia were significantly more frequent with doublets (HRs 2.13, 1.01-4.49 and 1.84, 1.29-2.63 respectively). Compared with single-agents, doublets significantly improved ORR but not OS. They induced significantly more frequent thrombocytopenia and anemia. The benefit-to-risk ratio of doublets in advanced NSCLC might be more favorable than that of single agents, based on ORR but not OS.


Long-Term Use of Short-Acting β2-Agonists in Patients With Adult-Onset Asthma.
Short-term studies have associated high use of short-acting β2-agonists (SABA) with increased risk of exacerbations, emergency visits, and asthma-related costs. However, no studies exist on long-term SABA use, and previous studies on the topic have not included information about adherence to inhaled corticosteroids (ICS) nor disease control, both affecting the need of SABA. To evaluate the clinical characteristics of SABA and ICS usage in newly diagnosed adult-onset asthma patients during a 12-year follow-up period. In the Seinäjoki Adult Asthma Study, 203 patients with adult-onset asthma were followed for 12 years. Information on dispensed SABA and ICS during the follow-up was obtained from the Finnish Social Insurance Institution. High SABA use was defined as ≥36 canisters in 12 years, corresponding to an average of ≥3 dispensed canisters/y. Patients were dispensed median 6 (interquartile range: 3-16) SABA canisters and 48 (18-67) ICS canisters over 12 years, corresponding to 2 (1-4) and 11 (5-16) puffs/week, respectively. Only 10% of the patients were classified as high SABA users during this period. Obesity (body mass index ≥30) and high Airways Questionnaire 20 symptom scores at baseline predicted high long-term SABA use (incidence rate ratio: 1.53 [1.01-2.30] and 1.04 [1.00-1.08], respectively). High SABA users had higher ICS adherence, higher blood neutrophil counts, more comorbidities, and used more oral corticosteroid and antibiotic courses versus low SABA users. High SABA use was infrequent in patients with confirmed adult-onset asthma. However, as high SABA use is associated with more severe asthma, these patients should be recognized in clinical practice.


Acid sphingomyelinase (aSMase) deficiency leads to abnormal microglia behavior and disturbed retinal function.
Mutations in the acid sphingomyelinase (aSMase) coding gene sphingomyelin phosphodiesterase 1 (SMPD1) cause Niemann-Pick disease (NPD) type A and B. Sphingomyelin storage in cells of the mononuclear phagocyte system cause hepatosplenomegaly and severe neurodegeneration in the brain of NPD patients. However, the effects of aSMase deficiency on retinal structure and microglial behavior have not been addressed in detail yet. Here, we demonstrate that retinas of aSMase(-/-) mice did not display overt neuronal degeneration but showed significantly reduced scotopic and photopic responses in electroretinography. In vivo fundus imaging of aSMase(-/-) mice showed many hyperreflective spots and staining for the retinal microglia marker Iba1 revealed massive proliferation of retinal microglia that had significantly enlarged somata. Nile red staining detected prominent phospholipid inclusions in microglia and lipid analysis showed significantly increased sphingomyelin levels in retinas of aSMase(-/-) mice. In conclusion, the aSMase-deficient mouse is the first example in which microglial lipid inclusions are directly related to a loss of retinal function.


Targeting the interleukin-17 immune axis for cancer immunotherapy.
The role of IL-17 in cancer remains controversial. Emerging evidence suggests that during early oncogenesis IL-17 supports tumor growth, whereas in established tumors IL-17 production by γδ and Th17 cells potentiates antitumor immunity. Consequently, γδ and Th17 cells are attractive targets for immunotherapy in the IL-17 immune axis. To optimize IL-17-based immunotherapy, a deeper understanding of the cytokines dictating IL-17 production and the polarity of γδ and Th17 cells is critical. Here, we delve into the dichotomous roles of IL-17 in cancer and provide insight into the tumor microenvironment conducive for successful IL-17-based γδ and Th17 cell immunotherapy.


Mitogen-activated protein kinase signaling causes malignant melanoma cells to differentially alter extracellular matrix biosynthesis to promote cell survival.
Intrinsic and acquired resistance to drug therapies remains a challenge for malignant melanoma patients. Intratumoral heterogeneities within the tumor microenvironment contribute additional complexity to the determinants of drug efficacy and acquired resistance. We use 3D biomimetic platforms to understand dynamics in extracellular matrix (ECM) biogenesis following pharmaceutical intervention against mitogen-activated protein kinases (MAPK) signaling. We further determined temporal evolution of secreted ECM components by isogenic melanoma cell clones. We found that the cell clones differentially secrete and assemble a myriad of ECM molecules into dense fibrillar and globular networks. We show that cells can modulate their ECM biosynthesis in response to external insults. Fibronectin (FN) is one of the key architectural components, modulating the efficacy of a broad spectrum of drug therapies. Stable cell lines engineered to secrete minimal levels of FN showed a concomitant increase in secretion of Tenascin-C and became sensitive to BRAF(V600E) and ERK inhibition as clonally- derived 3D tumor aggregates. These cells failed to assemble exogenous FN despite maintaining the integrin machinery to facilitate cell- ECM cross-talk. We determined that only clones that increased FN production via p38 MAPK and β1 integrin survived drug treatment. These data suggest that tumor cells engineer drug resistance by altering their ECM biosynthesis. Therefore, drug treatment may induce ECM biosynthesis, contributing to de novo resistance.


Effects of angiotensin converting enzyme inhibition in adult polycystic kidney disease.
The pathogenesis of hypertension in autosomal-dominant polycystic kidney disease (ADPKD) is unclear, but increased activity of the renin-angiotension system may contribute. The renal and systemic hemodynamic response to lisinopril, an angiotension converting enzyme (ACE) inhibitor, in patients with ADPKD without renal failure was compared with the response in matched unaffected family members. Mean blood pressure and renal vascular resistance decreased in the affected group after lisinopril, with no significant change in the unaffected group. Glomerular filtration rate (GFR) was unchanged and therefore filtration fraction fell significantly. Changes in urinary excretion of 6-keto-PGF1 alpha and kallikrein suggested that increased renal synthesis of PGI2 or activation of the renal kallikrein-kinin system were not likely to be responsible for the hemodynamic effects. The acute decrease in renal vascular resistance without change in GFR suggests that ACE inhibition may have a particular value in the treatment of hypertension associated with ADPKD which should be assessed by further long-term studies.


Ultrastructural localization of fibronectin in bone marrow of the embryonic chick and its relationship to granulopoiesis.
Fibronectin was immunolocated in embryonic chick bone marrow by the use of both a direct peroxidase conjugated antiserum and an indirect Streptavidin bridge technique. Fibronectin is located in the extravascular granulopoietic compartment and, to a lesser extent, in the vascular, erythropoietic compartment. There is no evidence of fibronectin being associated with blood-stromal cell interactions involving either erythropoiesis or thrombopoiesis. However, mature thrombocytes display a substantial surface coat containing fibronectin. Much of the fibronectin appears to be situated on surfaces of those fibroblastic stromal cells which support granulopoiesis. Fibronectin containing extracellular material connects surfaces of developing granulocytes with surfaces of stromal cells. Fibronectin is a surface component of granulocytes as well as nearby stromal cells. However, there appear to be fewer ferritin particles per unit of surface on granulocytic cells. Many of the ferritin particles are not clearly associated with amorphous matrix material at cell surfaces. Immunocytochemical attempts to identify laminin were unsuccessful. These studies indicate that fibronectin is situated at sites where it could mediate adhesive interaction between granulopoietic cells and their stromal cells. Furthermore, cell surface-matrix interaction involving fibronectin could mediate migration of blood cells within the extravascular spaces.


Purification of 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase from mouse epidermis.
Ornithine decarboxylase was purified at least 1500-fold from mouse epidermis pretreated with five consecutive doses of 12-O-tetradecanoylphorbol-13-acetate and 3-isobutyl-1-methylxanthine at 3- to 4-day intervals. Following DEAE-cellulose chromatography and ammonium sulfate precipitation, ornithine decarboxylase was purified further by affinity chromatography. Ornithine decarboxylase was then radioactively labeled by covalently binding [3H]-alpha-difluromethylornithine to the enzyme following polyacrylamide gel electrophoresis under non-denaturing conditions. Following sodium dodecyl sulfate polyacrylamide gel electrophoresis and silver staining of protein, a band was identified that corresponded to a molecular weight of approx. 56,000, coincident with a peak of radioactivity. This is the first study to purify ornithine decarboxylase from mouse epidermis.


Cleaning Disposal of High-Iron Bauxite Residue Using Hydrothermal Hydrogen Reduction.
The hydrothermal hydrogen reduction process for treating high-iron bauxite residue (red mud) was investigated, and the optimum conditions of alumina extraction as well as the enrichment of iron minerals were verified by experiments. Results show that the surface magnetization of Al-goethite under the function of hydrogen reduction accelerates its conversion to hematite and/or magnetite. This conversion releases the substituted Al in goethite as well as the undigested gibbsite/boehmite and further enriches the iron content in residue. After hydrothermal hydrogen reduction with H2/Red mud ratio of 0.085 mol/20 g at 270°C for 60 min, the alumina relative recovery ratio reaches 95.40% and the grade of iron (total iron in the form of iron element) in the residue can be enriched to 55.85%. Further, co-processing of the obtained iron-rich residue in the steel industry can achieve a significant reduction of red mud discharge.


Evaluation of fixed and variable hospital costs due to Clostridium difficile infection: institutional incentives and directions for future research.
Economic analysis of Clostridium difficile infection (CDI) should consider the incentives facing institutional decision-makers. To avoid overstating the financial benefits of infection prevention, fixed and variable costs should be distinguished. To quantify CDI fixed and variable costs in a tertiary referral hospital during August 2015. A micro-costing analysis estimated CDI costs per patient, including the additional costs of a CDI outbreak. Resource use was quantified after review of patient charts, pharmacy data, administrative resource input, and records of salary and cleaning/decontamination expenditure. The incremental cost of CDI was €75,680 (mean: €5,820 per patient) with key cost drivers being cleaning, pharmaceuticals, and length of stay (LOS). Additional LOS ranged from 1.75 to 22.55 days. For seven patients involved in a CDI outbreak, excluding the value of the 58 lost bed-days (€34,585); costs were 30% higher (€7,589 per patient). Therefore, total spending on CDI was €88,062 (mean: €6,773 across all patients). Potential savings from variable costs were €1,026 (17%) or €1,768 (26%) if outbreak costs were included. Investment in an antimicrobial pharmacist would require 47 CDI cases to be prevented annually. Prevention of 5%, 10% and 20% CDI would reduce attributable costs by €4,403, €8,806 and €17,612. Increasing the incremental LOS attributable to CDI to seven days per patient would have increased costs to €7,478 or €8,431 (if outbreak costs were included). As much CDI costs are fixed, potential savings from infection prevention are limited. Future analysis must consider more effectively this distinction and its impact on institutional decision-making.


Sandwich enzyme-linked immunosorbent assay compared with Pastorex latex agglutination test for diagnosing invasive aspergillosis in immunocompromised patients.
The performance of a direct sandwich enzyme-linked immunosorbent assay (ELISA) for detecting Aspergillus galactomannan was compared with that of the Pastorex Aspergillus antigen latex agglutination (LA) test by using 532 serum samples from 61 patients at risk for invasive aspergillosis. The ELISA gave positive results earlier in the course of infection than did the LA test. A sensitivity of 70% and a specificity of 86% were obtained for the LA test and corresponding values of 90 and 84% were obtained for the ELISA when a series of serum samples was employed.


Getting their voices heard: three cases of public participation in environmental protection in China.
By comparing three cases of environmental activism in China, our paper answers the following three questions about public participation in environment protection in China: (1) what are the drivers for public participation, (2) who are the agents leading the participation, and (3) do existing laws facilitate public participation? We find heightened public awareness of environmental degradation and increasing anxieties over health and property values drive people to fight for more political space to influence decisions that have an impact on the environment. Despite the promises one finds in the letter of Chinese laws, Chinese society lacks a meaningful institutional framework to allow public participation, even in the area of environmental protection. The Chinese government mainly passively responds to public demands on an ad hoc basis, with no institutional commitment for engaging the public on environmental issues. This is unfortunate, because public policies without adequate public input are doomed to be clouded by illegitimacy.


Properties of cloned T cells that mediate delayed-type hypersensitivity against ovalbumin in mice.
Cloned T-cell lines that mediate delayed-type hypersensitivity (DTH) against soluble protein antigen, ovalbumin (OA), were established in (C57BL/6 X DBA/2)F1 mice and their properties were examined. They induced antigen-specific delayed-type footpad reactions, characterized histologically by a predominant mononuclear cell infiltration, when transferred intravenously into syngeneic mice. Morphologically, they were medium or large lymphoblasts with granules in the cytoplasm and expressed Lyt 1 cell surface antigens. One of them proliferated antigen specifically under the presence of both C57BL/6 and F1 accessory cells, while others proliferated antigen specifically only under the presence of F1 accessory cells. They also produced macrophage-activating factor (MAF) and substances which mediate a DTH-like footpad inflammatory reaction with a maximum 6 hr after injection into the footpad of normal mice, when incubated in the presence of specific antigen and specific accessory cells in a serum-free medium for 24 hr. These results demonstrate that cloned DTH-effector T cells, established here against soluble protein antigen, are Lyt 1-positive, large lymphoblasts and that they produce MAF and footpad-reactive inflammatory substances antigen specifically under the presence of specific accessory cells.


Suppressed vascular Rho-kinase activation is a protective cardiovascular mechanism in obese female mice.
Obesity is the number one cardiovascular risk factor for both men and women and is a complex condition. Although a sex dimorphism on vascular function has already been noted, the underlying processes remain unclear. The Rho-kinase pathway has a unique role in controlling vascular tone, and in obese male mice, hyperactivation of this system results in worsened vascular constriction. We investigated whether female mice exhibit decreased Rho-kinase activation as a protective mechanism in obesity. We exposed male and female mice to a high-fat diet (HFD) for 14 weeks. At the end, energy expenditure, glucose tolerance, adipose tissue inflammation, and vascular function were investigated. Male mice were more sensitive to HFD-induced body weight gain, glucose tolerance, and inflammation than female mice. After establishing obesity, female mice demonstrated increase in energy expenditure, characterized by an increase in heat, whereas male mice did not. Interestingly, obese female mice, but not male, displayed attenuated vascular contractility to different agonists, such difference was blunted by inhibition of Rho-kinase, which was accompanied by a suppressed Rho-kinase activation, measured by Western blot. Finally, aortae from obese male mice displayed an exacerbated inflammation, whereas obese female demonstrated a mild vascular inflammation. In obesity, female mice demonstrate a vascular protective mechanism-suppression of vascular Rho-kinase-to minimize the cardiovascular risk associated with obesity, whereas male mice do not generate any adaptive response. Future investigations can help to understand how Rho-kinase becomes suppressed in female during obesity.


The importance of trochanteric lag screws to achieve primary stability in cementless fixation of the RM hip prosthesis.
To allow the bony incorporation of a cementless prosthesis it is important to achieve stability at the time of operation. To neutralize tension and torsional stresses the RM-shaft prosthesis is fixed with two lag screws in the trochanteric part of the femur. By measuring the applied torque intraoperatively we could demonstrate that the threads of the screws found a better grip when inserted from the bone to the prosthesis. Thus, the stronger fixation of the screws enhanced the primary stability of the cementless prosthesis.


Rab6 membrane association is dependent of Presenilin 1 and cellular phosphorylation events.
Processing of the amyloid precursor protein (APP) by alpha-secretase precludes the formation of beta-amyloid (Abeta). Therefore, the increase of cleavage by alpha-secretase upon stimulation by protein kinase C (PKC) is of potential therapeutic interest for Alzheimer's disease (AD). Unknown is whether phosphorylation by PKC increases alpha-secretase-mediated cleavage directly or indirectly, for example, by modulation of APP trafficking. Because modulation of Rab6-mediated transport has been shown to affect APP processing, we investigated the regulation of Rab6 membrane association by PKC and its relation to PS1. We show that in fibroblasts, Rab6 membrane association is PKC dependent, an effect strongly potentiated by inhibition of calcineurin. Moreover, we demonstrate that this regulation of Rab6 membrane association is dependent on PS1. The possible implications for APP processing and AD are discussed.


A study of calcergy in the rat induced by the implantation of polyurethane sponges soaked in lead acetate.
Polyurethane sponges were soaked in a 5 mg/ml solution of lead acetate, dried, and implanted subcutaneously in rats. Sponges soaked in distilled water were implanted as controls. The reaction to the sponges was studied from 5 h to 140 days after implantation, utilising sponge dry weight gain, rate of ingrowth of granulation tissue, histology and electron microscopy. Five hours after implantation, test sponges showed lead phosphate deposits in the central sponge zone and by one day the deposits stained positively for calcium. Transmission electron microscopy (TEM) showed needle-shaped crystals of hydroxyapatite. Ingrowth of granulation tissue into test sponges was delayed. Breakdown of the sponge matrix was observed in control sponges after 140 days. This model highlighted the physicochemical nature of the calcergic reaction, implicating fluid transudates/exudates in the initial stages.


Metoclopramide-mediated prolactin secretion in patients with idiopathic hypogonadotropic hypogonadism: effect of testosterone therapy.
The secretion of prolactin (PRL) after intravenous metoclopramide was evaluated in six prepubertal subjects with idiopathic isolated hypogonadotropic hypogonadism before and after repeated testosterone (T) injections. The PRL response to metoclopramide was markedly blunted before T treatment, but both the basal and metoclopramide-stimulated PRL secretion became normal after 4 to 15 months of intramuscular T enanthate, although in three of the subjects, serum T was low at the time of the repeat study. These results confirm that the pituitary lactotrophs are normal in this disorder and suggest that the attenuated response observed in the untreated patients is due to the chronic and persistent exposure of the lactotrophs to an environment low in T. The effect of exogenous T on the lactotrophs persists for several weeks after T is discontinued.


The dawn of the Middle Paleolithic in Atapuerca: the lithic assemblage of TD10.1 from Gran Dolina.
The Atapuerca localities present evidence of a long series of hominin occupations from the Early Pleistocene onward and are a key site for understanding the continuity and discontinuity of Western European technological and settlement dynamics. The TD10 unit from Gran Dolina is located in the upper part of the sequence and divided into four lithostratigraphic subunits (TD10.4 to TD10.1, from bottom to top) dated between ca. 450 ka and ca. 250 ka (Marine Isotope Stage 11 to Marine Isotope Stage 8). The technological analysis of the lithic assemblages belonging to the TD10.1 sequence aims to determine the trends among its archeological levels and check its relation to late Middle Pleistocene technological evolution and site functionality. Archeostratigraphic studies have identified several occupation events within its approximately 1.5 m of thickness, whose artifact densities and occupational models differ. However, no remarkable technical differences have been observed among them. Lithic assemblages from those events show more evolved features than other Atapuerca Mode 2 assemblages. These changes are reflected in the selective raw material management strategies; more hierarchized and predetermined reduction methods; and the progressive decrease of large cutting tools in the lithic assemblages with respect to flake tools, the latter defined by a greater typological diversification. These technological changes did not lead to a clear break with respect to previous technological models and were accompanied by other sporadic but significant changes in subsistence and behavioral strategies (bone tools and retouchers; lithic recycling, and so on), which were consolidated during the Middle Paleolithic. Hence, the archeological record from the TD10.1 subunit of Gran Dolina reflects a local stratigraphic transition from Mode 2 to Mode 3 technocomplexes, paralleling that observed in other sites in southwestern Europe.


Screening and identification of a novel B-cell neutralizing epitope from Helicobacter pylori UreB.
Urease plays a crucial role in the survival and pathogenesis of Helicobacter pylori (H. pylori), and antibody neutralizing the urease activity may be implicated for the protection against H. pylori infection. Previously, a neutralizing monoclonal antibody (MAb) 6E6 against UreB of H. pylori was developed. In this work, we try to identify the B-cell epitope recognized by neutralizing MAb 6E6. Following screening a series of truncated proteins of UreB, an epitope was primarily localized in the aa 200-230 of UreB. Subsequently, we screened the overlapping synthetic peptides covering the aa 200-230 and identified a novel B-cell epitope (U(211-225), IEAGAIGFKIHEDWG) that was recognized by specific MAb 6E6. The newly identified epitope may help understanding of the protective immunity against H. pylori and be implicated for vaccine development.


2,3-Dihydroxybenzoic acid is a product of human aspirin metabolism.
2,3-Dihydroxybenzoic acid is present in blood plasma and urine of healthy human volunteers after aspirin ingestion. Its identity has been confirmed by mass spectrometry and by electrochemical analysis. Methods for its identification and measurement are described. The concentration of 2,3-dihydroxybenzoic acid is much lower than that of 2,5-dihydroxybenzoic acid, salicylic acid or salicyluric acid.


Primary synovial chondromatosis mimicking medial meniscal tear in a young man.
Magnetic resonance imaging has recently become a noninvasive and cost-effective diagnostic tool for meniscal pathology in the knee. We report an unusual case of primary synovial chondromatosis for which the clinical diagnosis was medial meniscal tear but magnetic resonance imaging also showed a displaced torn meniscus, causing a so-called "double meniscus sign." The patient was definitely diagnosed and successfully treated with arthroscopy. We discuss the clinical diagnostic and therapeutic challenges, and the possible pathogenesis.


Eucommiae cortex polysaccharides attenuate gut microbiota dysbiosis and neuroinflammation in mice exposed to chronic unpredictable mild stress: Beneficial in ameliorating depressive-like behaviors.
Chronic stress alters gut microbiota composition, as well as induces inflammatory responses and behavioral deficits. Eucommiae cortex polysaccharides (EPs) have been reported to remodel gut microbiota and ameliorate obesogenic diet-induced systemic low-grade inflammation, but their role in stress-induced behavioral and physiological changes is poorly understood. Male Institute of Cancer Research (ICR) mice were exposed to chronic unpredictable stress (CUMS) for 4 weeks and then supplemented with EPs at a dose of 400 mg/kg once per day for 2 weeks. Behavioral test-specific antidepressant and anxiolytic effects of EPs were assessed in FST, TST, EPM, and OFT. Microbiota composition and inflammation were detected using 16S ribosomal RNA (rRNA) gene sequencing, quantitative RT-PCR, western blot, and immunofluorescence. We found that EPs ameliorated gut dysbiosis caused by CUMS, as evidenced by increasing the abundance of Lactobacillaceae and suppressing the expansion of the Proteobacteria, thereby mitigating intestinal inflammation and barrier derangement. Importantly, EPs reduced the release of bacterial-derived lipopolysaccharides (LPS, endotoxin) and inhibited the microglia-mediated TLR4/NFκB/MAPK signaling pathway, thereby attenuating the pro-inflammatory response in the hippocampus. These contributed to restoring the rhythm of hippocampal neurogenesis and alleviating behavioral abnormalities in CUMS mice. Correlation analysis showed that the perturbed-gut microbiota was strongly correlated with behavioral abnormalities and neuroinflammation. This study did not clarify the causal relationship between EPs remodeling the gut microbiota and improved behavior in CUMS mice. EPs exert ameliorative effects on CUMS-induced neuroinflammation and depression-like symptoms, which may be strongly related to their beneficial effects on gut microbial composition.


Observer design for a class of nonlinear piecewise systems. Application to an epidemic model with treatment.
Susceptible Exposed Infectious and Recovered epidemic model endowed with a treatment function (SEIR-T model) is a well-known model used to reproduce the behavior of an epidemic, where the susceptible population and the exposed population need to be estimated to predict and control the propagation of a contagious disease. This paper focuses on the nonlinear observer design for a class of nonlinear piecewise systems including SEIR-T models. For this purpose, two changes of coordinates are provided to transform the considered systems into an extended nonlinear observer normal form, on which a high gain observer can be applied. Then, the proposed method is applied to a SEIR-T model. Finally, simulation results are given to show its efficiency.


[Lipoatrophia semicircularis in the male. Coincidence of arterial variations and micro-traumas as a possible disease cause].
Semicircular lipoatrophy is a new entity with horizontal depressions involving half the circumference of thigh, on the antero-lateral aspect. After seven female patients we observed this condition for the first time in the male. Therefore semicircular lipoatrophy is not specific to the female. The cause could not be determined clinically, nor by biochemical, immunological or histological methods. In our opinion semicircular lipoatrophy represents an ischemic atrophy of the fatty tissue, manifested by repeated microtraumata (corners of wash-basins, dressing tables or desks). The perfusion on the antero-lateral aspect of the thighs is tenous, especially when the course of the lateral femoral circumflex artery varies from the normal. In this case semicircular anastomotic areas become ischemic and horizontal bands of lipoatrophy result.


Preadult competition between colonizing populations of Drosophila subobscura and established populations of Drosophila simulans in Chile.
The palearctic species Drosophila subobscura was detected for the first time in Chile and probably in the Americas in 1978. At present, its distribution area extends between 29°54'S and 53°40'S, where it has become abundant in both domestic and wild environments, depending on the latitude and the season of the year (appearing at maximum frequency in early spring). The seasonal fluctuations of D. subobscura are the inverse of those of D. simulans, which shares the same habitat in certain regions. Under laboratory conditions D. subobscura proved to be a poor competitor during the larval developmental period in relation to D. simulans, which on the contrary seemed to be "facilitated" by the larvae of the other species. However, the existence of D. subobscura in Chile is most probably due to its population flush at a time when D. simulans is at low density.


Growth and radiation sensitivity of the MLS human ovarian carcinoma cell line grown as multicellular spheroids and xenografted tumours.
The growth characteristics and the radiation sensitivity of multicellular spheroids of the MLS human ovarian carcinoma cell line grown in spinner culture in atmospheres of 5% CO2 in air or 5% CO2, 5% O2 and 90% N2 were studied and compared to that of MLS xenografted tumours. The spheroids grew exponentially with a volume-doubling time of approximately 24 h up to a diameter of approximately 580 microns and then the growth rate tapered off, more for spheroids grown at the low than at the high oxygen tension. Thirty days after initiation, the spheroid diameters were approximately 1,500 microns at the low and 2,100 microns at the high oxygen tension. The tumour volume-doubling times were approximately 8 days (V less than 200 mm3) and 17 days (V = 1,000-4,000 mm3). The histological appearance of the spheroids and the tumours was remarkably similar; both developed large central necrosis and both were composed of epithelial cells and showed pseudoglandular structures with lumen. The spheroids were slightly less differentiated than the tumours. The intrinsic, cellular radiation sensitivity was independent of whether the cells were grown in vitro as spheroids or in vivo as tumours, as revealed by irradiating single cells from dissociated spheroids and tumours under aerobic conditions and intact spheroids and tumours under hypoxic conditions. Studies of 1,600 microns spheroids grown in 5% CO2 in air showed that the intrinsic radiation sensitivity of the chronically hypoxic cells was the same as that of acutely hypoxic cells. The fraction of radiobiologically hypoxic cells under these conditions was approximately 15% and similar to those of 9% (V = 200 mm3) and 28% (V = 2,000 mm3) found for the tumours. Spheroids with diameter of 1,200 microns did not show survival curves parallel to those for acutely hypoxic cells, i.e. they did not contain a measurable fraction of clonogenic cells at complete radiobiological hypoxia. The final portion of their survival curves represented partially hypoxic cells; the OERs were 1.6 and 1.3 for spheroids grown at the high and the low oxygen tension, respectively. The considerable similarity between the spheroids and the tumours suggests that MLS spheroids constitute a valuable in vitro model for studies of human tumour radiation biology and related physiological processes. MLS spheroids may be particularly useful in studies of therapeutic consequences of partial radiobiological hypoxia since complete hypoxia and different levels of partial hypoxia can be studied separately by varying spheroid size and the oxygen tension in the culture medium.


How do career barriers and supports impact nurse professional commitment and professional turnover intention?
This study examines how career barriers and supports (i.e., perceived discrimination, lack of advancement, human capital, and social capital) impact affective, normative, and continuance aspects of professional commitment and thus nurses' professional turnover intention. Professional commitment is known to influence professional turnover intention. However, little is known about how career barriers and supports contribute to professional commitment and reduce professional turnover intention. This study adopted a cross-sectional design and a survey to collect representative data in a major hospital in northern Taiwan. We used proportionate random sampling to ensure sample representativeness and obtained 524 responses. Perceived discrimination and lack of advancement were negatively related to affective professional commitment. Human capital was positively related to affective, normative, and continuance professional commitment. Social capital was positively related to normative professional commitment. All aspects of professional commitment were negatively related to professional turnover intention. Career barriers and supports have an important influence on professional commitment. Reduced barriers and enhanced support may therefore help reduce nurses' professional turnover intentions. Nursing managers could aim to lessen career barriers while increasing career support for nurses, helping strengthen nurses' professional commitment and retention.


Does peripheral hypocaloric parenteral nutrition benefit the postoperative patient? Results of a multicentric randomized trial.
To study the potential benefits of hypocaloric peripheral parenteral nutrition (HPPN) in medium to high risk surgical patients we compared this regimen with standard fluid therapy during the postoperative period. Seventy patients were randomised to receive HPPN, consisting of 1 g of amino acids and 2 g of polyols (sorbitol and xylitol) per Kg per day (n = 41), or 1500 ml of 5% glucose and 1500 ml of saline (n = 29). There were no differences in length of hospital stay, postoperative complications or weight loss between the two groups. Concentrations of short and long half-life plasma proteins were similar in both groups. Nitrogen balance was negative and the nitrogen retention was low (60%) in the HPPN group. We conclude that there are no discernible clinical advantages in giving HPPN postoperatively to patients undergoing medium or major severity elective surgery.


School enrollments during the COVID-19 pandemic: The case of New York.
This study extends the earlier literature on changes in school enrollment in the wake of the COVID-19 pandemic by using data for the second COVID-19 school year (2021-2022) from the state of New York. Contrary to expectations that the resumption of fully-live instruction would reverse the first COVID-19 year's declines in public school enrollment, we find that enrollment continued to drop sharply in the second COVID-19 school year, when schools were entirely back to in-person learning. These declines in enrollment vary substantially by grade, race and poverty and are robust to controlling for other COVID-19 related factors. In addition, we find mixed results for the number of private school students but significant increases in home-schooled students in the two COVID-19 years. The findings have important educational and fiscal implications.


Acute and chronic hormone and metabolite changes in lambs fed the beta-agonist, cimaterol.
The objective of this study was to determine if acute and chronic changes in circulating metabolic hormone and metabolite concentrations are associated with beta-agonist-induced nutrient repartitioning in young growing lambs. Two groups of 12 Dorset and Dorset-Finn cross ram lambs weighing 36 or 33 kg live weight were assigned to 3- or 6-week treatment intervals, respectively, to achieve similar slaughter weights. Six lambs within each treatment interval were fed ad libitum a complete mixed high-concentrate diet containing either 0 or 10 ppm cimaterol. During the first 12 hr of cimaterol administration plasma somatotropin (ST), thyroxine (T4), and triiodothyronine (T3) concentrations were not altered by treatment, but plasma insulin, glucose, non-esterified fatty acids (NEFA) and glycerol concentrations were elevated 2 hr after ingestion. These acute responses suggest direct stimulation of glycogenolysis and lipolysis by cimaterol, which is characteristic of beta-adrenergic alteration of carbohydrate and lipid metabolism. Chronic administration of cimaterol significantly decreased insulin concentrations by 36% and 52% at 3 and 6 weeks, respectively, while glucose concentrations remained unchanged. Serum IGF-I concentrations were not significantly altered by cimaterol. T4 levels were reduced 22.1% after 3 weeks of cimaterol treatment. Although plasma NEFA concentrations were chronically elevated 56% to 65% in lambs fed cimaterol, plasma glycerol concentrations remained at baseline levels. The relative changes in plasma NEFA and glycerol concentrations are consistent with a decreased rate of lipogenesis, rather than an increase in lipolysis.


Imaging the itinerant-to-localized transmutation of electrons across the metal-to-insulator transition in V2O3.
In solids, strong repulsion between electrons can inhibit their movement and result in a "Mott" metal-to-insulator transition (MIT), a fundamental phenomenon whose understanding has remained a challenge for over 50 years. A key issue is how the wave-like itinerant electrons change into a localized-like state due to increased interactions. However, observing the MIT in terms of the energy- and momentum-resolved electronic structure of the system, the only direct way to probe both itinerant and localized states, has been elusive. Here we show, using angle-resolved photoemission spectroscopy (ARPES), that in V2O3, the temperature-induced MIT is characterized by the progressive disappearance of its itinerant conduction band, without any change in its energy-momentum dispersion, and the simultaneous shift to larger binding energies of a quasi-localized state initially located near the Fermi level.


5,12-Diselena-3,4,13,14-tetra-aza-tri-cyclo[9.3.0.02,6]tetra-deca-3,13-diene.
The title compound, C8H8N4Se2, crystallizes in a non-symmetrical conformation with a dihedral angle between the heterocycles of 45.0 (3)° and a nearly strain-free tetra-methyl-ene tether. The crystal studied was non-merohedrally twinned with a fractional contribution of 0.342 (3) for the minor twin component.


Current developments in gastric cancer: from molecular profiling to treatment strategy.
Gastric cancer and gastro-oesophageal junction cancer represent a global health-care challenge. Despite the efficacy of improved chemotherapy and surgical options, these patients still have a poor prognosis. In advanced disease, only trastuzumab and some immune checkpoint inhibitors, such as nivolumab and pembrolizumab in addition to chemotherapy, have demonstrated consistent and reliable efficacy in patients with HER2-positive and PDL1-positive tumours, respectively. In this Review, we discuss the intrinsic characteristics of gastric and gastro-oesophageal cancer from the molecular and clinical perspectives and provide a comprehensive review of previously reported and ongoing phase II and III clinical trials with targeted agents and immunotherapy in advanced and localized settings. Finally, we suggest alternative strategies to help overcome current challenges in precision medicine and to improve outcomes for these patients.


Radiation Recall Dermatitis after Donor Lymphocyte Infusion for Adult T-Cell Leukemia Lymphoma Post-Allogeneic Stem Cell Transplant.
To our knowledge, this is the first case report describing radiation recall dermatitis (RRD) after donor lymphocyte infusion post-allogeneic stem cell transplant in a patient with acute T-cell leukemia lymphoma. Given its rare occurrence, unclear clinical characterization, and etiology, RRD remains poorly understood. In the setting of novel immunotherapies and recent development of COVID-19 mRNA vaccines, we aimed to better characterize RRD and its most likely pathogenesis in our patient's case.


Development and qualification of an antibody rapid deglycosylation method.
N-linked glycosylation can influence the biological activity and safety of an antibody as well as be a measure of the consistency of the production process. The released N-glycans is an important part of the development of a therapeutic antibody. The traditional method for N-glycan analysis requires complex and laborious sample preparation and lengthy analysis time. Two preparation steps with limited control are removal of the antibody backbone by ice-cold ethanol precipitation and water removal before 2-AB fluorescent dye labeling. Simplification of the sample preparation and better control of key steps that allows for the characterization/quantitation of glycans during all stages of development of a therapeutic antibody is desired. Recently Prozyme introduced a rapid deglycosylation kit and a rapid tagging kit that address some of these issues. The deglycosylation kit immobilizes the antibody on a membrane, thereby eliminating the precipitation step. An instant fluorescent tag kit eliminates the water removal before the 2-AB labeling step. In addition use of a new chromatography column can improve the glycan resolution and shorten the analysis time. The evaluation and qualification of the Rapid Deglycosylation Kit (RDK) and instant 2-AB tagging with the improved chromatography are highlighted.


Anaerobic degradation of hexachlorocyclohexane isomers in liquid and soil slurry systems.
Gamma-hexachlorocyclohexane (gamma-HCH or lindane), one of the most commonly used insecticides, has been mainly used in agriculture. Organochloride compounds are known to be highly toxic and persistent, causing serious water and soil pollution. The objective of the present study is the evaluation of the anaerobic degradation of alpha-, beta-, gamma-, delta-HCH in liquid and slurry cultures. The slurry system with anaerobic sludge appears as an effective alternative in the detoxification of polluted soils with HCH, as total degradation of the four isomers was attained. While alpha- and gamma-HCH disappeared after 20-40d, the most recalcitrant isomers: beta- and delta-HCH were only degraded after 102d. Intermediate metabolites of HCH degradation as pentachlorocyclohexane (PCCH), tetrachlorocyclohexene (TCCH), tri-, di- and mono-chlorobenzenes were observed during degradation time.


The effect of endogenous skin bacteria on burn wound infection.
Burn wound sepsis can be due to exogenous or endogenous bacteria. When rare organisms cause infection, exogenous sources are implicated. This sets into motion hospital infection control team searches, which are both exhausting and harassing to patients and staff. This study examines the skin bacteria present at admission and the frequency of endogenous infection in burn patients. Sixty-two patients with burns up to 92% of the total body surface area underwent unburned skin bacterial surveillance on admission and at weekly intervals using RODAC contact plates. Burn wounds were biopsied for quantitative and qualitative analyses. Morphologically dissimilar colonies were isolated and identified using standard gram-positive and gram-negative identification strips (Analytab Products, Inc. [API]). On admission, the patients harbored Staphylococcus species, many of which were burn wound sepsis were infected with the same organisms cultured from their unburned skin on admission. A subset of patients (14) grew methicillin-resistant Staphylococcus aureus from their wounds or other sites. A comparison with admission isolates showed identical susceptibilities. These data suggest skin is an endogenous source of infection in the burned patient.


P2-, but not P1-purinoceptors mediate formation of 1, 4, 5-inositol trisphosphate and its metabolites via a pertussis toxin-insensitive pathway in the rat renal cortex.
1. The adenosine receptor (P1-purinoceptor) agonists N6-cyclopentyladenosine and N-5'-ethyl-carboxamidoadenosine at concentrations up to 10 mumols 1(-1) affected neither basal, nor noradrenaline- and angiotensin II-stimulated formation of inositol-1-phosphate, inositol-1,4-bisphosphate, and inositol-1,4,5-trisphosphate in slices of rat renal cortex. 2. In contrast, adenine nucleotides (P2-purinoceptor agonists) markedly stimulated inositol phosphate formation. The observed rank order of potency adenosine-5'-O-(2-thiodiphosphate) (EC50 39 mumols 1(-1] greater than adenosine-5'-O-(3-thiotriphosphate) (587) greater than or equal to 5'-adenylylimidodiphosphate (App(NH)p, 899) greater than adenylyl-(beta, gamma-methylene)-diphosphate (4,181) was consistent with the interaction of the compounds with the P2Y-subtype of P2-purinoceptors. AMP and the ADP analogue (alpha, beta-methylene)-adenosine-5'-diphosphate were ineffective. ATP and ADP (less than or equal to 10 mmol 1(-1] did not produce a consistent increase, owing to their hydrolytic degradation in the incubation medium. 3. Whereas the inositol phosphate response to App(NH)p was linear only up to 5 min incubation, the time-dependent stimulation of noradrenaline declined at a slower rate. Following pre-exposure of the renal cortical slices to App(NH)p, renewed addition of App(NH)p caused no further enhancement in the accumulation of inositol phosphates, whilst noradrenaline was still capable of eliciting a response. This suggests that the apparent loss of responsiveness to App(NH)p is not due to substrate depletion or enzymatic inactivation, but most likely attributable to homologous desensitization of the purinoceptor. 4. Pretreatment of the animals with pertussis toxin caused a substantial reduction of functional Gi-protein, as indicated by the lack of [32P]-NAD incorporation in a membrane preparation of the renal cortex. Nevertheless, the increase in inositol phosphate formation induced by noradrenaline, angiotensin II, and App(NH)p was not significantly impaired. 5. We conclude that P2 gamma-purinoceptors are present in the renal cortex; these receptors stimulate formation of inositol phosphates via a pertussis toxin-insensitive pathway and undergo homologous desensitization. On the other hand, our results suggest that renal A,-adenosine receptors do not use stimulation of phosphoinositide breakdown as a transmembrane signalling system.