NVX-CoV2373-induced T- and B-cellular immunity in immunosuppressed people with multiple sclerosis that failed to respond to mRNA and viral vector SARS-CoV-2 vaccines.
Immunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is important, especially in people with multiple sclerosis (pwMS) on immunosuppressive therapies. This study aims to determine whether adjuvanted protein-based vaccine NVX-CoV2373 is able to induce an immune response to SARS-CoV-2 in pwMS with inadequate responses to prior triple mRNA/viral vector vaccination. We conducted a single-center, prospective longitudinal cohort study at the MS Center in Dresden, Germany. In total, 65 participants were included in the study in accordance with the following eligibility criteria: age > 18 years, immunomodulatory treatment, and insufficient T-cellular and humoral response to prior vaccination with at least two doses of SARS-CoV-2 mRNA (BNT162b2, mRNA-1273) or viral vector vaccines (AZD1222, Ad26.COV2.S). Intramuscular vaccination with two doses of NVX-CoV2373 at baseline and 3 weeks of follow-up. The development of SARS-CoV-2-specific antibodies and T-cell responses was evaluated. For the final analysis, data from 47 patients on stable treatment with sphingosine-1-phosphate receptor (S1PR) modulators and 17 on ocrelizumab were available. The tolerability of the NVX-CoV2373 vaccination was overall good and comparable to the one reported for the general population. After the second NVX-CoV2373 vaccination, 59% of S1PR-modulated patients developed antispike IgG antibodies above the predefined cutoff of 200 binding antibody units (BAU)/ml (mean, 1,204.37 [95% CI, 693.15, 2,092.65] BAU/ml), whereas no clinically significant T-cell response was found. In the subgroup of the patients on ocrelizumab treatment, 23.5% developed antispike IgG > 200 BAU/ml (mean, 116.3 [95% CI, 47.04, 287.51] BAU/ml) and 53% showed positive spike-specific T-cellular responses (IFN-gamma release to antigen 1: mean, 0.2 [95% CI, 0.11, 0.31] IU/ml; antigen 2: mean, 0.24 [95% CI, 0.14, 0.37]) after the second vaccination. Vaccination with two doses of NVX-CoV2373 was able to elicit a SARS-CoV-2-specific immune response in pwMS lacking adequate immune responses to previous mRNA/viral vector vaccination. For patients receiving S1PR modulators, an increase in anti-SARS-CoV-2 IgG antibodies was detected after NVX-CoV2373 vaccination, whereas in ocrelizumab-treated patients, the increase of antiviral T-cell responses was more pronounced. Our data may impact clinical decision-making by influencing the preference for NVX-CoV2373 vaccination in pwMS receiving treatment with S1PR modulation or anti-CD20 treatment.


Analysis of Predictive Factors for Early Response to Ruxolitinib in 320 Patients with Myelofibrosis From the Polish Adult Leukemia Group (PALG) Registry.
Ruxolitinib is widely used in myelofibrosis (MF). However, some patients do not optimally respond and require more efficacious treatment. Our analysis aimed to establish predictors of ruxolitinib response. We designed a multicenter, retrospective analysis of the efficacy of ruxolitinib treatment in patients with MF in 15 Polish hematology centers. As responses to ruxolitinib occur within the first 6 months, we used this point to evaluate the efficacy of treatment. Symptoms response was defined as ≥50% reduction of the MF constitutional symptoms assessed by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). Spleen response was defined as ≥50% reduction of the difference between the spleen's baseline length and the upper limit norm measured by ultrasonography. 320 MF patients were enrolled. At 6 months of therapy, the spleen response was detected in 140 (50%) patients, and symptoms response in 241 patients (76%). Multivariable analysis identified leukocytosis <25 G/L (OR 2.06, 95%CI: 1.12-3.88, P = .0200), and reticulin fibrosis MF 1 (OR 2.22, 95%CI: 1.11-4.46, P = .0249) contributed to better spleen response. The time interval between MF diagnosis and ruxolitinib administration shorter than 3 months, and platelets ≥150 G/L (OR 1.69, 95% CI 1.01-2.83, P = .0466) influenced symptoms response. Establishing predictive factors for ruxolitinib response is particularly important given the potential for new therapies in MF. In patients with a low likelihood of responding to ruxolitinib, using other JAK inhibitors or adding a drug with a different mechanism of action to ruxolitinib may be of clinical benefit.


Shared decision making for the allergist.
Shared decision making (SDM) is becoming more commonly appreciated and used in medical practice as a way to empower patients who are facing treatment preference-sensitive conditions, such as allergic rhinitis, atopic dermatitis, food allergy, and persistent asthma. The purpose of this review is to educate the allergy health care provider about how SDM works and provide practical advice and allergist-specific SDM resources. PubMed and online patient decision aid resources. Studies and reviews relevant to SDM and patient decision aids relevant to the allergy health care provider were selected for discussion. There are ethical, practical, economic, and psychological imperatives for the implementation of quality SDM, particularly for chronic diseases. Many benefits and barriers of SDM have been identified and models have been developed to encourage implementation of quality SDM. For the allergy health care provider, SDM for asthma has been shown to improve adherence, outcomes, and patient satisfaction with care. Patient decision aids are useful tools for SDM and have recently been developed for allergen immunotherapy, severe asthma, and atopic dermatitis. Effective SDM has been shown to improve adherence and lead to better outcomes. SDM should be universally implemented as a key component of patient-centered health care. Allergy health care providers should work with their patients to reach treatment decisions that align with their values and preferences.


Neural circuit-specific gene manipulation in mouse brain in vivo using split-intein-mediated split-Cre system.
Neural network studies require efficient genetic tools to analyze individual neural circuit functions in vivo. Thus, we developed an advanced circuit-selective gene manipulating tool utilizing anterograde and retrograde adeno-associated viruses (AAVs) encoding split-intein-mediated split-Cre. This strategy can be applied to visualize a specific neural circuit as well as manipulate multiple genes in the circuit neurons. Here, we describe the production and purification of the AAVs, viral injection to the mouse brain, and imaging analysis for a specific neural circuit. For complete details on the use and execution of this protocol, please refer to Kim et al. (2022).


IL-18BPa:Fc cooperates with immunosuppressive drugs in human whole blood.
The proinflammatory cytokine interleukin (IL)-18 appears to be involved in the pathogenesis of diseases associated with immunoactivation and inflammation. Consequently, blockage of IL-18 bioactivity by use of IL-18 binding protein (IL-18 BP) is likely a promising therapeutic concept. In the present study, we investigated immunomodulatory activities of IL-18 BPa:Fc in human whole blood cultures. We report that IL-18 BPa:Fc (200 ng/mL) significantly inhibited lipopolysaccharide (LPS, 10 ng/mL)/IL-12 (5 ng/mL)-induced release of interferon-gamma (IFNgamma) and matrix metalloproteinase-9 (MMP-9) from whole blood cultures of healthy donors. Notably, IL-18 BPa:Fc (200 ng/mL) further reinforced dexamethasone (5 nM)- or mycophenolic acid (2 microM)-mediated reduction of LPS/IL-12-induced IFNgamma production by an additional 50.5 or 49.9%, respectively. To investigate effects of IL-18 BP:Fc in the context of autoimmune diseases, experiments were performed with whole blood obtained from patients with systemic lupus erythematosus or Wegener's granulomatosis undergoing immunosuppressive therapy. After ex vivo stimulation with LPS (10 ng/mL), production of IFNgamma and MMP-9 was determined. Both mediators likely contribute to renal inflammation frequently seen in these diseases. In accord with the aforementioned data, LPS (10 ng/mL)-induced IFNgamma was significantly reduced by coincubation with IL-18 BPa:Fc at 200 ng/mL. IL-18 BPa:Fc also inhibited production of MMP-9. The present data demonstrate that IL-18 BPa:Fc has the potential to amplify anti-inflammatory actions of immunosuppressive drugs, and thus may prove to be a valuable novel pharmacological component in the treatment of human autoimmune diseases.


Fermentation Kinetics of Selected Dietary Fibers by Human Small Intestinal Microbiota Depend on the Type of Fiber and Subject.
An underexplored topic is the investigation of health effects of dietary fibers via modulation of human small intestine (SI) microbiota. A few previous studies hint at fermentation of some dietary fibers in the distal SI of humans and pigs. Here the potential of human SI microbiota to degrade dietary fibers and produce metabolites in vitro is investigated. Fructans, galacto-oligosaccharides, lemon pectins, and isomalto/malto-polysaccharides are subjected to in vitro batch fermentations inoculated with ileostomy effluent from five subjects. Fiber degradation products, formation of bacterial metabolites, and microbiota composition are determined over time. Galacto- and fructo-oligosaccharides are rapidly utilized by the SI microbiota of all subjects. At 5h of fermentation, 31%-82% of galacto-oligosaccharides and 29%-89% fructo-oligosaccharides (degree of polymerization DP4-8) are utilized. Breakdown of fructo-oligosaccharides/inulin DP ≥ 10, lemon pectin, and iso-malto/maltopolysaccharides only started after 7h incubation. Degradation of different fibers result in production of mainly acetate, and changed microbiota composition over time. Human SI microbiota have hydrolytic potential for prebiotic galacto- and fructo-oligosaccharides. In contrast, the higher molecular weight fibers inulin, lemon pectin, and iso-malto/maltopolysaccharides show slow fermentation rate. Fiber degradation kinetics and microbiota responses are subject dependent, therefore personalized nutritional fiber based strategies are required.


Growth of moderately halophilic bacteria isolated from sea water using phenol as the sole carbon source.
Moderately halophilic bacteria utilizing phenol as the sole carbon source were isolated by selective enrichment from sea water. The isolate (Gram-negative motile rods) was identified as Deleya venusta. It grew well in the presence of up to 1600 mg/L of phenol and 8% NaCl under aerobic conditions. When the cells were treated with chloramphenicol prior to the addition of phenol they did not utilize added phenol, even after prolonged incubation. Thus, the enzymes necessary for phenol metabolism appeared to be inducible.


Peretinoin after curative therapy of hepatitis C-related hepatocellular carcinoma: a randomized double-blind placebo-controlled study.
Effective prophylactic therapies have not been established for hepatocellular carcinoma recurrence. Peretinoin represents one novel option for patients with hepatitis C virus-related hepatocellular carcinoma (HCV-HCC), and it was tested in a multicenter, randomized, double-blind, placebo-controlled study. Patients with curative therapy were assigned to one of the following regimens: peretinoin 600, 300 mg/day, or placebo for up to 96 weeks. The primary outcome was recurrence-free survival (RFS). Of the 401 patients initially enrolled, 377 patients were analyzed for efficacy. The RFS rates in the 600-mg group, the 300-mg group, and the placebo group were 71.9, 63.6, and 66.0 % at 1 year, and 43.7, 24.9, and 29.3 % at 3 years, respectively. The primary comparison of peretinoin (300 and 600-mg) with placebo was not significant (P = 0.434). The dose-response relationship based on the hypothesis that "efficacy begins to increase at 600 mg/day" was significant (P = 0.023, multiplicity-adjusted P = 0.048). The hazard ratios for RFS in the 600-mg group vs. the placebo group were 0.73 [95 % confidence interval (CI) 0.51-1.03] for the entire study period and 0.27 (95 % CI 0.07-0.96) after 2 years of the randomization. Common adverse events included ascites, increased blood pressure, headache, presence of urine albumin, and increased transaminases. Although the superiority of peretinoin to placebo could not be validated, 600 mg/day was shown to be the optimal dose, and treatment may possibly reduce the recurrence of HCV-HCC, particularly after 2 years. The efficacy and safety of peretinoin 600 mg/day should continue to be evaluated in further studies.


The epigenetically-regulated miR-663 targets H-ras in K-562 cells.
miR-663 is a tumour suppressor that is potentially regulated by modification of CpG islands. Whether aberrant methylation is one of the reasons for miR-663 down-regulation in some malignant cells and whether miR-663 targets oncogenes warrants further research. In the present study, we report that the CpG islands in the upstream region of pre-miR-663 are aberrantly methylated in the k-562 cell line and in the white blood cells of some chronic myelogenous leukaemia patients, and also that H-ras is one of the genes targeted by miR-663. Over-expression of miR-663 may suppress proliferation of the k-562 cell line in part by enhancing cell apoptosis.


Postoperative cerebral infarction and arrhythmia after pulmonary lobectomy in Japan: a retrospective analysis of 77,060 cases in a national clinical database.
To investigate the incidence of postoperative cerebral infarction after curative lobectomy, its association with the type of lobectomy, and how postoperative new-onset arrhythmia contributes to postoperative cerebral infarction. The subjects of this analysis were 77,060 patients who underwent curative lobectomy for lung cancer between 2016 and 2018 according to the National Clinical Database. Incidences of postoperative cerebral infarction and postoperative new-onset arrhythmia were analyzed. Moreover, mediation analysis was performed to evaluate the causal pathway between postoperative new-onset arrhythmia and postoperative cerebral infarction. Postoperative cerebral infarction occurred in 110 (0.7%) patients after left upper lobectomy and in 85 (0.7%) patients after left lower lobectomy. Left upper lobectomy and left lower lobectomy were associated with a higher likelihood of postoperative cerebral infarction than right lower lobectomy. Left upper lobectomy was the strongest independent predictor of postoperative new-onset arrhythmia. However, in the mediation analysis, the odds ratio for cerebral infarction did not change after the addition of the factor of postoperative new-onset arrhythmia. Cerebral infarction occurred significantly more often not only after left upper lobectomy, but also after left lower lobectomy. Postoperative new-onset arrhythmia was less likely to be related to cerebral infarction after left upper lobectomy.


Attributional and behavioral changes following two behavior management interventions with hyperactive boys: a follow-up study.
In a 6-month follow-up study of 2 interventions with hyperactive boys, different patterns of improvement were observed for an intervention which focused on self-control and 1 which employed contingent social reinforcement. Of the 2 manipulations, self-control methods produced significantly stronger long-term benefits in terms of the child's increased perception of personal control over academic outcomes; social reinforcement, on the other hand, produced significantly stronger long-term benefits in terms of teacher ratings of hyperactivity or impulsivity (Conners Teacher Rating Scale). Both interventions produced stable changes in terms of decreased behavioral impulsivity as measured by qualitative error scores on the Porteus Mazes.


Influence of streptozotocin (STZ)-induced diabetes, dextrose diuresis and acetone on cisplatin nephrotoxicity in Fischer 344 (F344) rats.
The following studies examined the impact of the diabetic state on cisplatin nephrotoxicity. This study also investigated the potential mechanisms for diabetes mediated reduction of cisplatin toxicity. A diabetic state was induced in male Fischer 344 (F344) rats after intraperitoneal (i.p.) injection of 27-35 mg/kg STZ. Cisplatin (5 mg/kg, i.p.) nephrotoxicity was examined in normoglycemic and diabetic rats after 48 and 96 h. Cisplatin was nephrotoxic within 96 h to normoglycemic animals as indicated by an increased kidney weight, marked elevations in serum BUN levels as well as significant P less than 0.05) decreases in renal cortical slice accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA). Cisplatin failed to depress renal cortical slice accumulation of PAH and TEA in the diabetic rats. Cisplatin was also less effective in increasing BUN levels or kidney weight in diabetic rats. Further studies investigated the impact of glycosuric diuresis and ketone bodies on cisplatin nephrotoxicity. Dextrose diuresis of normoglycemic rats failed to reduce the effect of cisplatin on BUN levels, kidney weight and renal cortical slice uptake of PAH and TEA. Acetone pretreatment of normoglycemic rats also did not reduce cisplatin nephrotoxicity. These results indicate: (1) cisplatin nephrotoxicity is attenuated in the experimental diabetic state, (2) diabetes does not reduce cisplatin nephrotoxicity through glycosuric diuresis and (3) ketone body accumulation does not modulate cisplatin nephrotoxicity.


Hepatobiliary cystadenocarcinoma with rapid growth: report of a case.
We describe a case of histologically proven hepatobiliary cystadenocarcinoma with an emphasis on the longterm clinical course. The patient was a 75-year-old man who had been diagnosed as having a simple hepatic cyst at our hospital and had been followed up by abdominal sonography (US) for about 10 years. However, the lesion subsequently showed a sudden increase in size and a marked change in US findings, i.e., from a benign hepatic cyst to a complete solid lesion. Contrast-enhanced US revealed the lesion to be filled with fine vessels. This rapid change led us to strongly suspect a hepatobiliary cystadenocarcinoma and, thus, left lateral segmentectomy was performed. The patient is doing well 6 months after the surgical treatment.


Stable Co(II)-based coordination polymer as fluorescence sensor for the discriminative sensing of biomarker methylmalonic acid.
Three novel Co-based coordination polymers including {[Co(L)(μ3-O)1/3]2}n (1), {[Co(L)(bimb)]}n (2) and {[Co(L)(bimmb)1/2]}n (3) (H2L = 2,6-di(4-carboxylphenyl)-4-(4-(triazol-1-ylphenyl))pyridine), bimb = 1,4-bis(lmidazol) butane, bimmb = 1,4-bis(imidazole-1-ylmethyl)benzene) were successfully prepared under solvothermal conditions and characterized. Single-crystal X-ray diffraction analyses revealed that 1 possesses a 3D architecture composed of a trinuclear cluster [Co3N3(CO2)6(μ3-O)], 2 exhibits a 2D new topological framework with the point symbol (84·122)(8)2, whereas 3 shows a unique six-fold interpenetrated 3D framework with a (63·82·10)2(63)2(8) topology. Impressively, all of them can function as a highly selective and sensitive fluorescent sensor for the biomarker methylmalonic acid (MMA) via fluorescence quenching. The low detection limit, reusability and high anti-interference performance together make 1-3 become promising sensors for the practical detection of MMA. Furthermore, the successful application of MMA detection in urine sample was demonstrated, which may be a potential candidate for the further development of clinical diagnostic tools.


Pneumocephalus following an epidural blood patch procedure: an unusual cause of severe headache.
Pneumocephalus is a rare complication of anesthetic procedures involving the epidural space. We report the case of a 36-year-old woman who developed a severe headache due to pneumocephalus that occurred during an epidural blood patching procedure. This report reviews the blood patch procedure and its attendant complications. Emergency physicians should be aware of the potential complications of this commonly performed procedure and include iatrogenic pneumocephalus in the differential diagnosis of severe headache in the proper clinical scenario.


Novel electrochemical method to activate biochar derived from spent coffee grounds for enhanced adsorption of lead (Pb).
Biochar (BC) has received much attention as a promising adsorbent that can be exploited to remove heavy metals in domestic and wastewater. The adsorption capacity of BC is, however, relatively low compared to that of conventional adsorbents, and its performance is inversely proportional to its stability. Various chemical and physical methods have been tried to address these limitations, but BC activation still generates too much acidic or alkaline wastewater. Here we propose a novel electrochemical method and compare its lead (Pb) adsorption capacity to that of acid- and alkaline-based approaches. We found that electrochemical activation significantly increased the number of hydroxyl and carboxylic groups on the BC surface, which led to an increase in Pb absorption from 27 % (pristine BC) to 100 % because the oxygenated-functional groups contributed to the adsorption of Pb. Pb capacity was 1.36, 2.64, 3.31, and 5.00 mg g-1, corresponding to pristine, acidic, alkaline, and electrochemical activation, respectively. The Pb absorption capacity of electrochemically activated BC was also higher than that of acid- and alkali-activated BC, which we attribute to the observed increases in oxygen ratio and surface area. Moreover, the adsorption rate of BC after electrochemical activation was 190 times faster and its capacity was 2.4 times higher than that of pristine BC. These findings show that the electrochemical activation of BC results in greater adsorption capacity than conventional methods.


Corrigendum: ArfX2 GTPase Regulates Trafficking From the Trans-Golgi to Lysosomes and Is Necessary for Liver Abscess Formation in the Protozoan Parasite Entamoeba histolytica.
[This corrects the article DOI: 10.3389/fcimb.2021.794152.].


Assay systems for screening food components that have anti-proliferative and anti-invasive activity to rat ascites hepatoma cells: In vitro and ex vivo effects of green tea extract.
We have developed in vitro and ex vivo assay systems for screening food components and natural substances that suppress the proliferation and/or invasion of a rat ascites hepatoma cell line of AH109A and have used them to study the effect of green tea extract. AH109A cells were found to penetrate underneath the monolayer of primary cultured mesothelial cells isolated from Donryu rat mesentery in the presence of 10% newborn bovine serum. Green tea extract inhibited this AH109A penetration in a dose dependent manner and also inhibited AH109A proliferation in vitro dose-dependently. Green tea tannin, the major polyphenolic substances in green tea extract, also inhibited the proliferation and invasion of AH109A in vitro in a dose dependent manner. When rat serum obtained 0.5 h after oral intubation of green tea extract was added to the culture media instead of newborn bovine serum at a concentration of 10%, the invasion of AH109A was significantly inhibited as compared to control rat serum (before green tea extract intubation); the inhibitory effect lasted for 1 h and disappeared 3 h after oral intubation of green tea extract, but those rat sera showed no inhibition of AH109A proliferation. These results suggest that green tea extract has an inhibitory effect on the invasion of AH109A both in vitro and ex vivo, but on the proliferation of AH109A only in vitro, and that these assay systems are effective for the screening of food components which inhibit tumor cell proliferation and invasion.


High-resolution aliphatic side-chain assignments in 3D HCcoNH experiments with joint H-C evolution and non-uniform sampling.
We describe an efficient NMR triple resonance approach that correlates, at high resolution, protein side-chain and backbone resonances. It relies on the combination of two strategies: joint evolution of aliphatic side-chain proton/carbon coherences using a backbone N-H based HCcoNH reduced dimensionality (RD) experiment and non-uniform sampling (NUS) in two indirect dimensions. A typical data set containing such correlation information can be acquired in 2 days, at very high resolution unfeasible for conventional 4D HCcoNH-TOCSY experiments. The resonances of the aliphatic side-chain protons are unambiguously assigned to their attached carbons through the analysis of the 'sum' and 'difference' spectra. This approach circumvents the tedious process of manual resonance assignments using HCcH-TOCSY data, while providing additional resolving power of backbone N-H signals. A simple peak-list based algorithm has been implemented in the IBIS software for rapid automated backbone and side-chain assignments.


Effect of Surgery at Primary and Metastatic Sites in Patients With Stage IV Breast Cancer.
There is no clear evidence of a survival benefit of resection of the primary tumor, or distant site resection (metastasectomy) in patients with stage IV breast cancer. This retrospective analysis of stage IV breast cancer using the National Cancer Database. To evaluate variables associated with surgery at the primary site, we used univariate analyses followed by multivariate logistic regression. Consequently, we evaluated the impact of lumpectomy, mastectomy or metastasectomy on survival by conducting multivariate Cox regression survival analyses on the following groups: all stage IV patients; a subset of those with only one metastatic site; and another subset with metastasis to multiple distant sites. A total of 54,871 stage IV breast cancer patients were included in this analysis. Variables associated with the use of surgery at the primary were: age, race, Charlson/Deyo score, insurance and facility type, involved breast quadrant, receptor status, N stage, extent of metastasis, and year of diagnosis. Survival analysis showed that both lumpectomy (median overall survival [OS], 45 months) and mastectomy (median OS, 44 months) were associated with better OS compared to no surgery (median OS, 22 months). The statistical effect was larger in the subgroup with metastasis to one site, but still significant in the subgroup with multiple metastatic sites. Distant site resection also yielded a survival benefit. In patients with metastasis to only one site, metastasectomy was associated with better OS when that site was the liver, lung, or brain.


Iloprost affects in vitro maturation and developmental competence of bovine oocytes.
Prostacyclin (PGI2) is synthesised in oviductal fluid and enhance the embryo development during the preimplantation period. The objective of the present study was to determine the effect of an analogue of prostacyclin (iloprost) on the in vitro maturation (IVM) and the developmental competence of bovine oocytes. Cumulus oocyte complexes (COCs) were cultured in maturation medium with iloprost (0.5 μM) for 24 h. We found that iloprost assisted maturation rates and cumulus cell expansion of bovine oocytes, and it increased the mRNA expression of genes related to cumulus expansion: ADAM17, AREG, and TNFAIP6 and cathepsin genes (CTSK and CTSS). Moreover, iloprost reduced the occurrence of apoptosis in COCs and promoted an antiapoptotic balance in the transcription of genes involved in apoptosis (BAX and BCL2). COCs treatment with iloprost during IVM also reduced intracellular reactive oxygen species (ROS) levels, while glutathione (GSH) levels and the mRNA expression of antioxidant genes CAT and GPx4 were markedly increased. We also showed that an analogue of PGI2 influenced the mitochondrial status via distribution rates of mitochondria and mitochondrial membrane potential in oocytes. Although, iloprost-enhanced maturation had no direct effect on number of embryos cleaved, it increased blastocyst rates of bovine embryos as well as proportion of expanded blastocysts. These results indicate that the supplementation of maturation medium with iloprost is beneficial for the maturation efficiency and developmental competence of bovine oocytes.


Cost analysis of adult-adult living donor liver transplantation in Tokyo University Hospital.
Living donor liver transplantation (LDLT) is now a well established treatment modality for end-stage liver diseases, but the financial aspects of LDLT have not yet been fully investigated. The purpose of this study was to determine the overall direct cost of adult-adult LDLT in Japan and to identify the factors associated with the high cost. The direct cost of initial admission for LDLT was determined in a retrospective analysis of data from hospital charts and databases. The records for 100 consecutive adults who underwent LDLT from January 2004 to February 2006 at our center were reviewed, and clinical and financial data of all recipients and donors were analyzed. The median direct total cost for LDLT was $82,017 (range $51,189-438,295). Of this, the median cost for donors was $15,011 (range $12,354-23,251). A multivariate stepwise logistic regression model for overall cost of transplantation revealed that donor age [odds ratio (OR) = 1.1, p = 0.02], acute renal failure (OR = 24, p = 0.007), and posttransplant plasma exchange (OR = 72, p = 0.01) were associated with higher cost. When the models were repeated with preoperative patient and donor factors alone, donor age (OR 1.1, p = 0.008) and model for end stage liver disease score (OR 1.2, p = 0.003) were associated with higher cost. Donor age, acute renal failure, and posttransplant plasma exchange were independent risk factors for the high cost of LDLT in Japan.


Bone remodeling of a femoral head after transtrochanteric rotational osteotomy for osteonecrosis associated with slipped capital femoral epiphysis: a case report.
A rare case of a 12-year-old boy on whom a joint-preserving operation for osteonecrosis after slipped capital femoral epiphysis (SCFE) was performed, is described. Firstly, in situ pinning was performed for acute-on-chronic SCFE. However, osteonecrosis and collapse of the femoral head occurred at 7 months after surgery. Secondly, transtrochanteric rotational osteotomy (TRO) was performed against progression of the collapse of the femoral head. Eight years of X-ray observation revealed bone remodeling at the osteonecrotic region. No documentation has been reported about the potential of bone remodeling of a femoral head with osteonecrosis after SCFE. This case indicates that a joint-preserving operation such as TRO is capable of promoting bone remodeling in such circumstances.


Viral protein R (Vpr)-induced neuroinflammation and its potential contribution to neuronal dysfunction: a scoping review.
HIV-associated neurocognitive disorders (HAND) are the result of the activity of HIV-1 within the central nervous system (CNS). While the introduction of antiretroviral therapy (ART) has significantly reduced the occurrence of severe cases of HAND, milder cases still persist. The persistence of HAND in the modern ART era has been linked to a chronic dysregulated inflammatory profile. There is increasing evidence suggesting a potential role of Viral protein R (Vpr) in dysregulating the neuroinflammatory processes in people living with HIV (PLHIV), which may contribute to the development of HAND. Since the role of Vpr in neuroinflammatory mechanisms has not been clearly defined, we conducted a scoping review of fundamental research studies on this topic. The review aimed to assess the size and scope of available research literature on this topic and provide commentary on whether Vpr contributes to neuroinflammation, as highlighted in fundamental studies. Based on the specified selection criteria, 10 studies (6 of which were cell culture-based and 4 that included both animal and cell culture experiments) were eligible for inclusion. The main findings were that (1) Vpr can increase neuroinflammatory markers, with studies consistently reporting higher levels of TNF-α and IL-8, (2) Vpr induces (neuro)inflammation via specific pathways, including the PI3K/AKT, p38-MAPk, JNK-SAPK and Sur1-Trpm4 channels in astrocytes and the p38 and JNK-SAPK in myeloid cells, and (3) Vpr-specific protein amino acid signatures (73R, 77R and 80A) may play an important role in exacerbating neuroinflammation and the neuropathophysiology of HAND. Therefore, Vpr should be investigated for its potential contribution to neuroinflammation in the development of HAND.


Management of atypical mycobacterial lymphadenitis in childhood: a review based on 380 cases.
The medical and surgical therapy of 82 cases of atypical mycobacterial adenitis from Dallas and 298 cases from the literature was reviewed. The 92% cure rate in 149 patients with total surgical excision alone was comparable to the 95% cure rate in 156 patients when excision was followed by antituberculous drug therapy. With incision and drainage in 63 patients the cure rate was 16% whether drugs were given or not. Ten patients were initially treated with antituberculous drugs alone and only one was cured. It is concluded that total surgical excision is definitive therapy for this disease and that antituberculous drugs should be used only when surgery cannot be performed or when complete excision is not possible.


Retinoids as potential chemopreventive agents in squamous cell carcinoma of the head and neck.
Although newer combined modality approaches, including neoadjuvant cytotoxic chemotherapy, for patients with squamous cell carcinoma (SCCA) of the head and neck have produced high initial complete response rates, they have not improved overall survival for patients with advanced disease. Vitamin A plays an essential role in the normal differentiation of epithelial tissues. Retinoids, analogs of vitamin A, are active in certain premalignant and malignant disorders including SCCA. Six studies, including one recently reported placebo-controlled randomized trial, have demonstrated the efficacy of retinoids in oral leukoplakia. Two studies (totalling 48 patients) have shown significant retinoid activity (67% overall complete response rate) in patients with aggressive, recurrent laryngeal papillomatosis. Two trials (including a randomized phase II trial) of isotretinoin in advanced, refractory SCCA of the head and neck have produced an objective response rate of 16%, which is comparable to that reported in single-agent studies with cytotoxic drugs. There is a need for further study of retinoids in head and neck cancer. The high initial response rates with current therapy and the high subsequent risks of local recurrence and of developing second primary tumors in head and neck cancer patients offer an excellent opportunity to investigate the use of retinoids as adjuvant therapy for this malignancy.


Association of the programmed death ligand-1 combined positive score in tumors and clinicopathological features in esophageal cancer.
The combined positive score (CPS) of the programmed death ligand-1 (PD-L1) 22C3 assay is a predictive marker of pembrolizumab monotherapy for advanced esophageal cancer (EC) patients. However, little is known about the association of the PD-L1 22C3 CPS with the clinicopathological features and heterogeneity of PD-L1 expression in EC in the Chinese population in a real-world setting. We examined the association of the PD-L1 22C3 CPS with clinicopathological characteristics in 533 EC specimens. Further, we compared 37 cases' different blocks of the same specimen and 50 paired primary/metastatic lymph node lesions to investigate the heterogeneity of PD-L1 expression. PD-L1 positive expression was observed in 45.0% of 533 EC patients, including 46.8% with squamous cell carcinoma, 15.4% with adenocarcinoma, 28.6% with basaloid squamous carcinoma, 42.9% with spindle cell carcinoma, and 33.3% with neuroendocrine tumors. PD-L1 positive expression was positively associated with lymph node metastasis (59.2% chance, p = 0.021) and venous/lymphatic invasion (66.3% chance, p = 0.029). PD-L1 expression was highly consistent in different paraffin blocks of the same surgically resected specimen (concordance rate: 86.5%, p = 0.000016) and a moderate consistency (concordance rate: 78.0%, p = 0.000373) for the primary and metastatic lymph node lesion comparison. This is a novel study which demonstrated a positive correlation between a high PD-L1 22C3 CPS and invasion/metastasis risk in EC surgical specimens. Both paired blocks and paired primary/metastatic lymph node lesions showed significant concordance. PD-L1 heterogeneity was inferred to be mainly related to positive mononuclear inflammatory cells (MICs), which might have substantial implications for clinical practice.


Diversity and chemical fingerprinting of endo-metabolomes from endophytes associated with Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang possessing antibacterial activity against multidrug resistant bacterial pathogens.
Serious infections caused by bacteria and their resistance to antibiotics are one of the biggest healthcare threats to mankind. Therefore, the present study aimed to isolate endophytes from medicinal plant Ampelopsis grossedentata, an endemic species of Western Hubei, China and to investigate its antibacterial efficacy and chemical diversity of the secondary metabolites. The antibacterial potential of the endophytes was evaluated by disc diffusion method against a panel of eleven type strains and some multidrug resistant pathogenic bacteria. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were estimated by broth microdilution using iodonitrotetrazolium chloride assay. Further, the chemical diversity of the metabolites was estimated using LC-Q-TOF-MS/MS and GC-MS fingerprinting. Four endophytic fungi were isolated from the tender shoot of A. grossedentata; they were identified as Fusarium graminearum TC-1, Phomopsis mali TC-3, Pestalotiopsis maculans TC-5 and Alternaria alternata TC-11. Among the endophytes screened, A. alternata TC-11 exhibited significant antibacterial activity with the zones of inhibition ranging from 13.72 ± 0.30 to 21.76 ± 0.53 mm against all the tested type strains and multidrug resistant bacterial pathogens. Further, it showed significant antibacterial activity with MIC values ranging from 0.37 to 3.00 μg/mL. The combined LC-Q-TOF-MS/MS and GC-MS analyses of active extract revealed that alternarian acid, altertenuol, dimethyl sulfone, docosane, dodecane, duclauxin, ergosta-4,6,8(14),22-tetraen-3-one, ethyl 6-cyano-5-oxo-1-phenyl-7-thiophen-2-yl-[1,2,4]triazolo[4,3-a]pyrimidine-3-carboxylate, heptacosane, linoleic acid, neodecanoic acid, oxiranylmethyl ester, pentadecane, verrulactone E, 2,6,11-Trimethyldodecane and 4-[(E,4R,6R)-11-(furan-3-yl)-6-hydroxy-4,8-dimethylundec-8-enyl]-2-hydroxy-2H-furan-5-one were the most abundant compounds present which were responsible for the significant antibacterial activity. To our knowledge, this is the first report of fungal endophytes isolated from the tender shoot of A. grossedentata with bacteriostatic and bactericidal activities. Our finding provides a new insight into the antibacterial potential of endophytes and envisages the possibility of using them for drug discovery.


Development of Antibody-Based Therapeutics Against West Nile Virus in Plants.
Since its discovery in 1937 in the West Nile district of Uganda, West Nile virus (WNV) has been one of the leading causes of mosquito-transmitted infectious diseases (Smithburn, Burke, Am J Trop Med 20:22, 1940). Subsequently, it spread to Europe, Asia, Australia, and finally North America in 1999 (Sejvar, Ochsner 5(3):6-10, 2003). Worldwide outbreaks have continued to increase since the 1990s (Chancey et al, Biomed Res Int 2015:376230, 2015). According to the Center for Disease Control and Prevention, more than 51,000 cases of WNV infection and nearly 2400 cases of WNV-related death were reported in the USA from 1999 to 2019. The estimated economic impact of WNV infections is close to 800 million dollars in the USA from 1999 to 2012 (Barrett, Am J Trop Med Hyg 90:389, 2014).


[Renal-rachidian venous trunk. Replacement of the left renal vein. A danger for the spinal cord (author's transl)].
In two cases of paraplegia due to an inondation of the intrarachidian plexus by venous blood from the left venal vein, we studied the frequency with which the renal-rachidian trunk connected the left renal vein and the intrarachidian plexus. We show in these rare cases how it is possible, with a simple procedure, the ligature of the renal-rachidian trunk, to bring about a marked regression in the paraplegia. This procedure has been carried out five times, and it should be seen within the wider framework of a serie of procedures on the cava system, which are now practised for more than forty years.


Anterior high-resolution OCT in the diagnosis and management of corneal squamous hyperplasia mimicking a malignancy: a case report.
Anterior high-resolution optical coherence tomography (HR-OCT) is a novel non-invasive in vivo imaging modality that can assist in the diagnosis and management of various ophthalmic pathologies. The implementation of diagnosing ocular surface lesions has been explored in previous studies, successfully revealing specific signs in some ocular lesions. This case report aims to exhibit a case of corneal squamous hyperplasia diagnosed via anterior HR-OCT, prior to surgical intervention. A 69 year-old male had blurred vision and foreign body sensation OD for several weeks. A rapidly-grown corneal mass was presented, showing an appearance of a grayish flesh-colored mass with elastic texture. Large vessels supplying the mass were also found. Anterior HR-OCT was performed, and the results suggested the lesion be benign hyperplasia. Superficial keratectomy was done, and the pathologic report showed mild-appearing epithelial squamous hyperplasia, which confirmed the analysis via anterior HR-OCT. In the categorization by Nanji, et al. of corneal surface diseases using anterior OCT, the comparative epithelial thickness (normal range: 47-68 μm); inferior border obscuration of epithelium (normal or benign inferior border: no shadowing); reflectivity of epithelial layer (normal: not hyper-reflective); abrupt transition (normal: no horizontally abrupt transition); and sub-epithelium analysis vary between benign and malignant lesions (normal: demarcated anterior to Bowman's layer), and the differences are systemically sorted. We applied all these characteristics to our patient as guidance, and the measurement results indicated the lesion be a benign lesion, which is consistent with the tissue pathology. Anterior HR-OCT is overall a non-invasive and timely method capable of assisting the diagnosis of ocular surface disease, predicting the qualities of a lesion, and determining the follow-up treatment plan.


Amount of hepatic fat predicts cardiovascular risk independent of insulin resistance among Hispanic-American adolescents.
Nonalcoholic fatty liver disease (NAFLD) has emerged as the major pediatric chronic liver disease, and it is estimated to affect more than one third of obese children in the U.S. Cardiovascular complications are a leading cause of increased mortality in adults with NAFLD and many adolescents with NAFLD already manifest signs of subclinical atherosclerosis including increased carotid intima-media thickness. Volume of intrahepatic fat was assessed in 50 Hispanic-American, overweight adolescents, using Magnetic Resonance Spectroscopy. Lipoprotein compositions were measured using Nuclear Magnetic Resonance. Plasma triglycerides (TG) (p=0.003), TG/HDL ratio (p=0.006), TG/apoB ratio (p=0.011), large VLDL concentration (p=0.019), VLDL particle size (p=0.012), as well as small dense LDL concentration (p=0.026) progressively increased across higher levels of hepatic fat severity, while large HDL concentration progressively declined (p=0.043). This pattern of associations remained even after controlling for gender, BMI, visceral fat, and insulin resistance. Our findings suggest that increased hepatic fat is strongly associated with peripheral dyslipidemia and the amount of fat in the liver may influence cardiovascular risk. Further studies are needed to longitudinally monitor dyslipidemia in children with NAFLD and to examine whether the reduction of hepatic fat would attenuate their long-term CVD risk.


[Correlation between in vitro release and in vivo absorption of sustained-releasing tablets of neostigmine bromide].
To determine the correlation between in vitro release and in vivo absorption of sustained-releasing tablets of neostigmine bromide. Water was used as dissolution medium to measured in vitro release of neostigmine bromide. After a single oral administration of 100 mg neostigmine bromide to rabbits, the plasma concentrations of neostigmine bromide in the rabbits were determined by HPLC. The compartment model and deconvolution method were employed to explain the in vitro-in vivo correlation. Using Y as cumulative in vitro release and Fa as percentage of absorption, the regression equation was established: Fa = 0.9298Y + 4.6074, r = 0.9961. The input function of R = 2.0163Y-11.242,r = 0.9270. The correlation between in vitro release and in vivo absorption of neostigmine bromide is good.


Better detection of Staphylococcus aureus nasal carriage by use of nylon flocked swabs.
Flocked swabs (Copan) were compared to rayon swabs (Copan) for the nasal detection of Staphylococcus aureus in 90 healthy volunteers sampled sequentially during a 5-week period. The use of flocked swabs improved the number of nasal carriers (P = 0.026), the number of positive specimens (P = 0.01), and the quantity of bacteria in positive samples (P = 0.004).


Financial reporting practices: a comprehensive evaluation.
A distinguishing characteristic of high performance organizations is a strong internal control structure-controls that ensure patient care, compliance with regulations, internal efficiencies, and financial reporting. It is controls on financial reporting that are receiving a great deal of attention under a new law, the Sarbanes-Oxley Act of 2002. Public companies are now required by law to document controls over financial reporting, in order to fully address exposures and the effectiveness of current controls. Though many healthcare organizations are not directly affected by the law, regulatory agencies could follow suit and require similar compliance. In fact, several states have introduced bills that require nonprofit organizations to adhere to portions of the act. This article provides a guide for organizations desiring to stay ahead of the curve.


Characterization of pore structure of chromatographic adsorbents employed in separation of monoclonal antibodies using size-exclusion techniques.
Structural properties of commercial chromatographic adsorbents designated for separation of monoclonal antibodies were investigated using size-exclusion techniques. A batch technique provided the specific pore volumes distributed among small, medium and large pores. Inverse size-exclusion chromatography yielded the partition coefficients of dextran solute probes in medium pores. These data were fitted with one- and two-parametric models corresponding to different pore-size distribution functions and the suitability of the individual models for the characterization of the examined materials was then assessed. The reliability of estimation of the parameters of log-normal distribution of cylindrical pores was investigated. Large uncertainties and a strong correlation of the mean pore diameter and width of distribution function were observed.


Surgical and transcatheter left atrial appendage closure in patients with atrial fibrillation and hypertrophic cardiomyopathy.
Patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) are at increased stroke risk in comparison to those with non-valvular AF not affected by HCM. To investigate the role of left atrial appendage closure (LAAC) in patients with HCM and AF. We identified patients with HCM and AF using the National Readmission Dataset. Patients were stratified based on LAAC status. The primary efficacy outcome was a composite of ischaemic and haemorrhagic stroke, TIA, and all-cause mortality. The primary safety outcome was a composite of major bleeding and pericardial complications. Patients were matched using inverse probability of treatment weighting. Cox-proportional hazard regression was applied to calculate the hazard ratio (HR) with a 95% confidence interval (CI) on matched cohorts. We identified 71 980 patients with HCM and AF. 1351 (1.9%) patients underwent LAAC. Two hundred and eighty-seven (21.2%) underwent transcatheter LAAC. LAAC was associated with a lower risk of the primary efficacy outcome (2.5% vs. 5.4%, HR: 0.38; 95% CI: 0.17-0.88; P = 0.024), the primary safety outcome (2.9% vs. 6.8%, HR: 0.39; 95% CI: 0.23-0.66, P = 0.001), and reduced major bleeding. The LAAC group trended towards a lower risk of ischaemic stroke and all-cause mortality. Surgical and transcatheter LAAC was associated with a lower risk of haemorrhagic stroke and major bleeding.


Metabolic changes of H2S in smokers and patients of COPD which might involve in inflammation, oxidative stress and steroid sensitivity.
Oxidative stress and inflammation play crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Most patients with COPD show a poor response to corticosteroids. Hydrogen sulfide (H2S ) has been implicated in the pathogenesis of COPD, but its expression and effects in lung tissue from COPD patients are not clear. In peripheral lung tissue samples from 24 patients, we found that compared with nonsmokers, the protein level of cystathionine-γ-lyase (CSE) was decreased in smokers and COPD patients. CSE mRNA increased but cystathionine-β-synthase (CBS) mRNA decreased in COPD patients. H2S donors increased glutathione and superoxide dismutase in CS exposed U937 cells and inhibited CS-induced TNF-α and IL-8 secretion. Dexamethasone alone had no effect on lipopolysaccharide (LPS) induced TNF-α release by alveolar macrophages from CS exposed rats, however the combination of dexamethasone and H2S donor significantly inhibited TNF-α release. Thus, H2S metabolism is altered in lung tissue of smokers and COPD patients. Supplementation of H2S protects against CS-induced oxidative stress and inflammation in macrophages and H2S on steroid sensitivity deserves further investigation.


Utility of d4-PGE2 as an internal standard to quantify endogenous levels of PGE1, PGE2, 19OH PGE1 and 19OH PGE2 in human seminal fluid by GC-MS-SIM.
Four prostaglandins-PGE1, PGE2, 19OH PGE1 and 19OH PGE2-were quantified in human seminal fluid by GC-MS-SIM using only the internal standard, d4-PGE2. Methods and calculations were developed to minimize errors inherent in using only one internal standard for quantifying four closely related prostaglandins. Preliminary data concerning the statistical significance of the difference found between PGE and 19OH PGE levels in fertile, azospermic and oligospermic men are reported.


The effects of resistance exercise on body composition and physical function in prostate cancer patients undergoing androgen deprivation therapy: an update systematic review and meta-analysis.
The aim of the meta-analysis was to explore effects of resistance exercise (RE) on body composition and physical function in patients with prostate cancer (PCa). We searched the electronic databases of Pubmed, Embase, Cochrane, and web of science. Published studies have been collected from these databases. Search terms include resistance training, strength training, RE, androgen suppression therapy, androgen deprivation therapy and PCa, with a deadline of 31 March 2022. These studies showed significant improvements of body composition(Lean body mass MD: 1.12 95% CI [0.48, 1.76], p < 0.01; Body fat rate MD: -1.12 95% CI [-1.99,-0.24], p < 0.05; Appendicular skeletal mass MD: 0.74 95% CI [0.45, 1.03], p < 0.01) and physical function (leg press MD: 77.95 95% CI [38.90, 117.00], p < 0.01; stair climb MD:-0.30 95% CI [-0.49, -0.12], p < 0.01). In addition, the improvement of Body fat mass (MD: -0.21 95% CI [-0.79, 0.37], p > 0.05), 400 m walk (MD: -21.74 95% CI [-45.53, 2.05], p > 0.05) and times up and go (MD: -0.50 95% CI [-1.03, 0.03], p > 0.05) were not obvious. Subgroup analyses showed that RE for ≥ 6 months (compared with RE intervention for < 6 months) and starting exercise immediately after androgen deprivation therapy (ADT) (compared with delayed exercise after ADT) resulted in more significant improvements in body composition. Furthermore, the results showed that the exercise intensity of 8-12 RM significantly improved body composition. RE seems to be a promising approach in order to improve body composition and physical function in PCa patients to offset their treatment-related side effects. RE should be used as a means of rehabilitation and care for PCa. Starting exercise immediately after ADT and extending exercise time while choosing the right intensity can better improve the patients' body composition and function. INPLASY202280019.


A comparison of verbal, sign, and simultaneous systems for the acquisition of receptive language by an autistic boy.
The effectiveness of verbal, sign, and simultaneous systems for the acquisition of receptive language by an autistic boy was investigated. The subject received training in all three methods by three teachers on each of 18 days. The order of methods and teachers was counterbalanced daily. The study incorporated a 27-word vocabulary composed of nouns, adjectives (colors), and verbs. The dependent variable was the number of correct responses during three daily sets of 20 assessment trials. Results suggest nonsignificant differences among the three methods. A secondary purpose was to investigate systematically the concomitant increases in subject-initiated interactions and eye contact accompanying the language training. The subject was observed during 10-min rest periods following each of the three daily language sessions; the occurrence of behaviors during timed intervals served as the dependent variables. Significant increases for subject-initiated interactions involving physical contact were observed.


Oocyte Scoring Enhances Embryo-Scoring in Predicting Pregnancy Chances with IVF Where It Counts Most.
Our center's quality improvement optimization process on many occasions anecdotally suggested that oocyte assessments might enhance embryo assessment in predicting pregnancy chances with in vitro fertilization (IVF). To prospectively compare a morphologic oocyte grading system to standard day-3 morphologic embryo assessment. We prospectively investigated in a private academically-affiliated infertility center 94 consecutive IVF cycles based on 6 criteria for oocyte quality: morphology, cytoplasm, perivitelline space (PVS), zona pellucida (ZP), polar body (PB) and oocyte size, each assigned a value of -1 (worst), 0 (average) or +1 (best), so establishing an average total oocyte score (TOS). Embryo assessment utilized grade and cell numbers of each embryo on day-3 after oocyte retrieval. Clinical pregnancy was defined by presence of at least one intrauterine gestational sac. Standard IVF cycles in infertile women. Predictability of pregnancy based on oocyte and embryo-grading systems. Average age for all patients was 36.5 ± 7.3 years; mean oocyte yield was 7.97± 5.76; Patient specific total oocyte score (PTOS) was -1.05 ± 2.24. PTOS, adjusted for patient age, was directly related to odds of increased embryo cell numbers (OR 1.12, P = 0.025), embryo grade (OR 1.19, P < 0.001) and clinical pregnancy [OR 1.58 (95%CI 1.23 to 2.02), P < 0.001]. Restricting the analysis to day three embryos of high quality (8-cell/ good grades), TOS was still predictive of clinical pregnancy (OR 2.08 (95%CI 1.26 to 3.44, P = 0.004). Among the 69 patients with embryos of Grade 4 or better available for transfer 23 achieved Clinical Pregnancy. When the analysis was restricted to the 69 transfers with good quality embryos (≥ Grade 4) the Oocyte Scoring System (TOS) (AUC±SE 0.863±0.044, oocyte score) provided significantly greater predictive value for clinical pregnancy compared to the embryo grade alone (AUC 0.646 ± 0.072, embryo grade) p = 0.015. Oocyte-scoring, thus, provides useful clinical information especially in good prognosis patients with large numbers of high quality embryos. This finding appears of particular importance at a time when many IVF centers are committing sizable investments to closed incubation systems with time-lapse photography, which are exclusively meant to define embryo morphology.


Submission or subversion: survival and resilience of Chinese international research students in neoliberalised Australian universities.
Although scholars have noted the detrimental nature of the various changes in higher education prompted by neoliberalism, its impact on the experiences of international Higher Degree by Research (HDR) students has yet to be adequately studied. Informed by Bourdieu's concepts of doxa, field, habitus, and capital, this paper examines the ways in which neoliberalism as doxa in the Australian higher education field has colonised the perception and practice of Chinese international HDR students whilst some students were able to demonstrate resilience to the pervasive neoliberal practices. The paper draws on a larger qualitative research project including interviews with 18 Chinese HDR students from four Australian universities. Data suggest that Chinese HDR research students gradually developed intensified dispositions of self-reliance and self-exploitation in response to neoliberal academic practices whilst others were enculturated into a floating habitus (or vulnerable position) in relation to academic publishing as they attempted to negotiate the tensions across fields and over time. Data further reveal that some participants demonstrated resilience to neoliberalism when empowered by their supervisors with less utilitarian and more critically reflexive supervisory practices. The paper argues that the embrace of neoliberalism in the Australian higher education field has become widespread yet controversial, and that thinking and enacting resilience sociologically may de-neoliberalise the higher education field in Australia and beyond.


Lifetime Exposure to Cigarette Smoke and Risk of Ovarian Cancer by T-cell Tumor Immune Infiltration.
Exposure to cigarette smoke, particularly in early life, is modestly associated with ovarian cancer risk and may impact systemic immunity and the tumor immune response. However, no studies have evaluated whether cigarette smoke exposure impacts the ovarian tumor immune microenvironment. Participants in the Nurses' Health Study (NHS) and NHSII reported on early life exposure to cigarette smoke and personal smoking history on questionnaires (n = 165,760). Multiplex immunofluorescence assays were used to measure markers of T cells and immune checkpoints in tumor tissue from 385 incident ovarian cancer cases. We used Cox proportional hazards models to evaluate HRs and 95% confidence intervals (CI) for developing ovarian tumors with a low (<median) or high (≥median) immune cell percentage by cigarette exposure categories. Women exposed versus not to cigarette smoke early in life had a higher risk of developing ovarian cancer with low levels of T cells overall (CD3+: HR: 1.54, 95% CI: 1.08-2.20) and recently activated cytotoxic T cells (CD3+CD8+CD69+: HR: 1.45, 95% CI: 1.05-2.00). These findings were not statistically significant at the Bonferroni-corrected P value of 0.0083. Adult smoking was not significantly associated with tumor immune markers after Bonferroni correction. These results suggest early life cigarette smoke exposure may modestly increase risk of developing ovarian tumors with low abundance of total T cells and recently activated cytotoxic T cells. Future research should focus on understanding the impact of exposures throughout the life course on the ovarian tumor immune microenvironment.


Thermodynamic stability explains the differential evolutionary dynamics of cytochrome b and COX I in mammals.
By using a combination of evolutionary and structural data from 231 species, we have addressed the relationship between evolution and structural features of cytochrome b and COX I, two mtDNA-encoded proteins. The interior of cytochrome b, in contrast to that of COX I, exhibits a remarkable tolerance to changes. The higher evolvability of cytochrome b contrasts with the lower rate of synonymous substitutions of its gene when compared to that of COX I, suggesting that the latter is subjected to a stronger purifying selection. We present evidences that the stability effect of mutations (ΔΔG) may be behind these differential behaviour.


Zinc transporter 3 and zinc ions in the rodent superior cervical ganglion neurons.
Previous studies have revealed that zinc-enriched (ZEN) terminals are present in all parts of the CNS though with great differences in intensity. The densest populations of both ZEN terminals and ZEN somata are found in telencephalic structures, but also structures like the spinal cord demonstrate impressive ZEN systems spreading terminals several segments around the respective ZEN somata. The present study evaluates whether sympathetic neurons in the superior cervical ganglia (SCG) are ZEN neurons, i.e. contain vesicles that have zinc transporter 3 (ZnT3) proteins in their membranes and contain zinc ions. ZnT3 immunoreactivity (IR) was found in the somata and processes in the postganglionic neurons of mouse SCG. Only a small fraction of neurons (less than 5%), expressed varying degrees of ZnT3. Colchicine treatment, however, increased the number of ZnT3-positive neurons three-fold, suggesting an accumulation of ZnT3 protein in the somata. A small proportion of the postganglionic axons revealed dotted accumulations of ZnT3 IR along their courses. Double labeling showed that all ZnT3-positive neurons and axons were also tyrosine hydroxylase-positive with strong immunofluorescence, while no colocalization was found between ZnT3 and the vesicular acetylcholine transporter (VAChT) or neuropeptide Y IR. VAChT-positive preganglionic neurons were found to terminate on ZnT3 neuronal somata. 6-Methoxy 8-para toluene sulfonamide quinoline fluorescence and zinc selenium autometallography (ZnSe(AMG)) revealed that a subgroup of SCG cells contained free or loosely bound zinc ions. It is therefore concluded that ZnT3 and zinc ions are present in a subpopulation of TH-positive, NPY-negative neurons in the rodent SCG, supporting the notion that vesicular zinc ions may play a special role in the peripheral sympathetic adrenergic system.


Microarrays--planning your experiment.
The rapid increase in the use of microarray studies has generated many questions on how to plan and design experiments that will effectively utilize this technology. Investigators often require answers to questions relating to microarray platforms, RNA samples, options for replication, allocation of samples to arrays, sample sizes, appropriate downstream analysis, and many others. Careful consideration of these issues is critical to ensure the efficiency and reliability of the actual microarray experiments, and will assist in enhancing interpretability of the experimental results.


Acute fatty liver of pregnancy: a case report a review of the literature.
Acute fatty liver of pregnancy (AFLP), a rare and potentially fatal disease, usually affects a primi gravida during the third trimester of pregnancy. We report a case of AFLP with a favourable maternal outcome.


Second harmonic generation on crystalline organic nanoclusters under extreme nanoconfinement in functionalized silica-benzil composites.
We demonstrate a series of organic-inorganic nanocomposite materials combining the mesoporous silica (PS) and benzil (BZL) nanocrystals embedded into its nanochannels (6.0-13.0 nm in diameter) by capillary crystallization. One aims to design novel, efficient nonlinear optical composite materials in which inactive amorphous host PS-matrix provides a tubular scaffold structure, whereas nonlinear optical functionality results from specific properties of the deposited guest BZL-nanocrystals. A considerable contraction of the BZL melt during its crystallization inside the silica nanochannels results in a formation of the texture consisting of (221)- and (003)-oriented BZL nanoclusters (22 nm in length), separated by voids. Specificity of the textural morphology similarly to the spatial confinement significantly influences the nonlinear optical features of composite PS:BZL materials being explored in the second harmonic generation (SHG) experiment. The light polarization anisotropy of the SHG response appears to be considerably reduced at channel diameters larger than 7 nm apparently due to the multiple scattering and depolarization of the light on randomly distributed and crystallographically oriented BZL-nanoclusters. The normalized SHG response decreases nonlinearly by more than one order of magnitude as the channel diameter decreases from 13.0 to 6.0 nm and vanishes when spatial cylindrical confinement approaches the sizes of a few molecular layers suggesting that the embedded BZL clusters indeed are not uniformly crystalline but are characterized by more complex morphology consisting of a disordered SHG-inactive amorphous shell, covering the channel wall, and SHG-active crystalline core. Understanding and controlling of the textural morphology in inorganic-organic nanocrystalline composites as well as its relationships with nonlinear optical properties can lead to the development of novel efficient nonlinear optical materials for the light energy conversion with prospective optoelectronic and photonic applications.


A Real-World Effectiveness Study Comparing a Priority Appointment, an Enhanced Contact Intervention, and a Psychotherapeutic Program Following Attempted Suicide.
To determine the comparative effectiveness of 3 real-practice preventive programs aimed at lowering the relapse risk following a suicide attempt: a single priority appointment with an outpatient psychiatrist, an enhanced contact intervention, and an individual psychotherapy program. This observational study was conducted in a sample of 1,492 suicide attempters from 3 catchment areas in Madrid, Spain, between 2013 and 2017. Relapse was defined as an emergency department return after a new attempt within a 1-year follow-up. Kaplan-Meier survival functions were obtained by intervention, and Cox proportional hazard regression models were used to estimate unadjusted and adjusted risks of relapse by intervention. Sex- and age-stratified analyses were also conducted. Covariates were age, sex, history of suicide attempts, history of psychiatric disorders, main ICD-10 psychiatric diagnostic groups, medical comorbidities, and family support. A total of 133 subjects (8.9%) relapsed. The psychotherapy group had a lower presence of known risk factors for suicide attempt. Individual psychotherapy and enhanced contact were more effective than a single priority appointment at reducing suicide reattempt, with a 40% lower relapse risk in adjusted models. Results did not differ after sex and age stratification. In a naturalistic clinical setting, patients exposed to individual psychotherapy or an enhanced contact intervention had a similar, lower relapse risk than the single priority appointment group.


Clinical and electrophysiological responses to dietary challenge in migraineurs.
Thirty eight patients with a history of diet-induced migraine were studied with recording of clinical responses, electroencephalography in resting state, in response to photic stimulation, and to hyperventilation and visual evoked potentials. Tests were carried out on an initial baseline day and on a second day, after challenge with chocolate, red wine, cheese, and fasting. Lateralized headache occurred in sixteen subjects (42%), four with scintillating scotomata. Electroencephalograms were abnormal on Day 1 and/or Day 2 in twelve subjects (32%), most abnormalities being non-specific slow waves. In three cases there were paroxysmal features. Electroencephalographic response to hyperventilation was calibrated and was found to be exaggerated in eight subjects (21%) on either Day 1 or Day 2; such response was not related to the occurrence of a headache. Photic simulation showed high frequency driving response (so called "H" response) in all 16 individuals who developed headache but in only 14 out of 22 (64%) who did not (p less than 0.01). Pattern reversal visual evoked responses were normal and failed to show any difference in latency or amplitude between headache responders and non-responders.


[Quantitative description of the process of cellular radiation inactivation. X. Closing remarks. Ways for further development of the concepts].
The series of communications to check the applicability of one of the most likely models of the loss of reproductive integrity of irradiated eukaryotic cells has been completed by this paper. Many radiobiologists accept the cytogenetic model but no one has analyzed mathematically its applicability. We have succeeded in explaining some significant experimental data and therefore our model is something more than a simple working hypothesis. In this paper the model is considered to prove its significance as the first approach to a more detailed study of the phenomenon.


Ultrastructural and morphological changes in Leishmania (Viannia) braziliensis treated with synthetic chalcones.
Cutaneous leishmaniasis has an estimated incidence of 1.5 million new cases per year and the treatment options available are old, expensive, toxic, and difficult to administer. Chalcones have shown good activity against several species of Leishmania. However few studies have discussed the mechanisms of action and drug target of this group of compounds in Leishmania. The synthetic chalcones that were evaluated in the present study were previously shown to exhibit activity against Leishmania (Viannia) braziliensis. The objective of the present study was to identify ultrastructural and morphological changes in L. (V.) braziliensis after treatment with three synthetic chalcones (1-3). Promastigotes were treated with chalcones 1-3 and evaluated by transmission and scanning electron microscopy. Cellular and nuclear morphology of the parasites, changes in membrane permeability, and DNA fragmentation in agarose electrophoresis gel were also investigated after exposure to synthetic chalcones. All three synthetic chalcones (1-3) induced ultrastructural alterations in mitochondria, intense vacuolization, two nuclei with rounding of parasites, and cellular and nuclear shrinkage. Chalcones 1-3 also induced no changes in membrane permeability, and presence of nucleosome-sized DNA fragments. Synthetic chalcones 1-3 induced ultrastructural and morphological changes, suggesting that chalcones 1-3 induce apoptosis-like cell death. Further studies should be conducted to elucidate other aspects of the action of these chalcones against Leishmania spp. and their use for the treatment of cutaneous leishmaniasis.


Assembling Metal Organic Layer Composites for High-Performance Electrocatalytic CO2 Reduction to Formate.
2D metal-organic-framework (MOF) based composites have emerged as promising candidates for electrocatalysis due to their high structural flexibility and fully exposed active sites. Herein, a freestanding metal-organic layer (MOL) with a 2D kgd (kagome dual) lattice was constructed with abundant surface oxygenate groups serving as anchoring sites to immobilize diverse guests. Taking Bi as an example, tetragonal Bi2 O3 nanowires can be uniformly grown on MOLs after solvothermal treatment, the structural evolution of which was followed by ex situ electron microscopy. The as-prepared Bi2 O3 /MOL exhibits excellent CO2 electroreduction activity towards formate reaching a specific current of 2.3 A mgBi -1 and Faradaic efficiencies of over 85 % with a wide potential range from -0.87 to -1.17 V, far surpassing Bi2 O3 /UiO (a 3D Zr6 -oxo based MOF) and Bi2 O3 /AB (Acetylene Black). Such a post-synthetic modification strategy can be flexibly extended to develop versatile MOL composites, highlighting the superiority of optimizing MOL-based composites for electrocatalysis.


The kisspeptin-1 receptor antagonist peptide-234 aggravates uremic cardiomyopathy in a rat model.
Uremic cardiomyopathy is characterized by diastolic dysfunction, left ventricular hypertrophy (LVH), and fibrosis. Dysregulation of the kisspeptin receptor (KISS1R)-mediated pathways are associated with the development of fibrosis in cancerous diseases. Here, we investigated the effects of the KISS1R antagonist peptide-234 (P234) on the development of uremic cardiomyopathy. Male Wistar rats (300-350 g) were randomized into four groups: (i) Sham, (ii) chronic kidney disease (CKD) induced by 5/6 nephrectomy, (iii) CKD treated with a lower dose of P234 (ip. 13 µg/day), (iv) CKD treated with a higher dose of P234 (ip. 26 µg/day). Treatments were administered daily from week 3 for 10 days. At week 13, the P234 administration did not influence the creatinine clearance and urinary protein excretion. However, the higher dose of P234 led to reduced anterior and posterior wall thicknesses, more severe interstitial fibrosis, and overexpression of genes associated with left ventricular remodeling (Ctgf, Tgfb, Col3a1, Mmp9), stretch (Nppa), and apoptosis (Bax, Bcl2, Casp7) compared to the CKD group. In contrast, no significant differences were found in the expressions of apoptosis-associated proteins between the groups. Our results suggest that the higher dose of P234 hastens the development and pathophysiology of uremic cardiomyopathy by activating the fibrotic TGF-β-mediated pathways.


Vitamin A preserves cardiac energetic gene expression in a murine model of diet-induced obesity.
Perturbed vitamin-A metabolism is associated with type 2 diabetes and mitochondrial dysfunction that are pathophysiologically linked to the development of diabetic cardiomyopathy (DCM). However, the mechanism, by which vitamin A might regulate mitochondrial energetics in DCM has previously not been explored. To test the hypothesis that vitamin-A deficiency accelerates the onset of cardiomyopathy in diet-induced obesity (DIO), we subjected mice with lecithin retinol acyltransferase (Lrat) germline deletion, which exhibit impaired vitamin-A stores, to vitamin A-deficient high-fat diet (HFD) feeding. Wild-type mice fed with a vitamin A-sufficient HFD served as controls. Cardiac structure, contractile function, and mitochondrial respiratory capacity were preserved despite vitamin-A deficiency following 20 wk of HFD feeding. Gene profiling by RNA sequencing revealed that vitamin A is required for the expression of genes involved in cardiac fatty acid oxidation, glycolysis, tricarboxylic acid cycle, and mitochondrial oxidative phosphorylation in DIO as expression of these genes was relatively preserved under vitamin A-sufficient HFD conditions. Together, these data identify a transcriptional program, by which vitamin A preserves cardiac energetic gene expression in DIO that might attenuate subsequent onset of mitochondrial and contractile dysfunction.NEW & NOTEWORTHY The relationship between vitamin-A status and the pathogenesis of diabetic cardiomyopathy has not been studied in detail. We assessed cardiac mitochondrial respiratory capacity, contractile function, and gene expression by RNA sequencing in a murine model of combined vitamin-A deficiency and diet-induced obesity. Our study identifies a role for vitamin A in preserving cardiac energetic gene expression that might attenuate subsequent development of mitochondrial and contractile dysfunction in diet-induced obesity.


Immunization Monitoring Program, Active: a model of active surveillance of vaccine safety.
In Canada since 1993 the nation's passive system for reporting postimmunization adverse events has been supplemented by the active surveillance of inpatients at 10 to 12 pediatric referral centers, a system referred to as the Immunization Monitoring Program, Active. Participating centers are located from coast-to-coast and receive referrals from every province and territory. Approximately 20 percent of the population aged 0 to 12 years lives in the immediate vicinity of these centers. Nurse monitors at each center search for numerous target conditions, including postimmunization adverse events and vaccine-preventable infections. Vaccine safety observations have included (1) a substantial decrease in the risk of the development of febrile seizures and hypotonic-hyporesponsive episodes since the country switched from whole-cell to acellular pertussis-containing vaccines, (2) no evidence for encephalopathy resulting from the latter vaccines, (3) a generally benign outcome with postimmunization thrombocytopenia cases, and (4) an unexpectedly high rate of disseminated bacille Calmette-Guérin infections among aboriginal infants. Concomitant disease surveillance has been important for sustaining the surveillance system because few postimmunization adverse events require hospital admission.


Correction: Javed et al. Zinc Oxide Nanoparticles (ZnO NPs) and N-Methylol Dimethyl Phosphonopropion Amide (MDPA) System for Flame Retardant Cotton Fabrics. Polymers 2022, 14, 3414.
The authors wish to make a correction to this paper [...].


The thermoregulatory function of diel vertical migration for a juvenile fish, Cottus extensus.
Juvenile sculpin (Cottus extensus) less than 30 mm long exhibit a diel vertical migration in the limnetic zone of Bear Lake (Utah-Idaho). Using mid-water and bottom trawls we found that these fish inhabit the bottom of the lake (5° C) during the day but migrate 30-40 m into the water column at night where they reside in the metalimnion or epilimnion at temperatures near 13-16°C. Larger fish do not migrate into the water column. Stomach analyses demonstrated that the young-of-the-year fish do not migrate into the water column to feed: from July to October their diet is 70-93% benthic ostracods and copepods, and pelagic prey are rarely consumed. Furthermore, gut fullness of the sculpin increases through the daylight period and decreases through the night, reaching minimum levels just before the dawn descent. Laboratory experiments demonstrated that the diel migration would increase digestion rate from 3%/h at profundal temperatures, to 22%/h in the warmer surface water, thus allowing the fish to empty their guts overnight and permit feeding the following day. Additionally, sculpin held in a temperature and feeding regime that mimicked that experienced by migrating fish grew 300% faster than those reared at 5° C. Given the overwhelming importance of fast growth for juvenile fishes, a post-feeding thermotaxs that increases digestion may be a common phenomenon increasing growth, and affecting the distribution and bioenergetic relationships of fish.


The use of Indonesian randu honey for chronic wounds in a patient with uncontrolled type 2 diabetes mellitus: A case report.
Honey has been recorded as having healing properties at a low cost. Many studies have been conducted related to Manuka honey, but studies about Indonesian randu honey are still limited. We report the use of Indonesian randu honey as a wound dressing on non-pressure chronic skin ulcers in uncontrolled T2DM patient. A 54-year-old man with uncontrolled T2DM came with an unrecovered wound. A thorough inspection revealed several exposed bones, tendons, muscles, and meniscus in the left lower leg region. It was supposed to be amputated, but he declined. He received insulin, debridement, STSG, and a combination of Indonesian randu honey dressing and VAC on the exposed wound before and after the debridement and STSG. There was skin graft lysis, and we intended to do another surgery, but he preferred to be an outpatient. As an outpatient, he received honey wound dressing and insulin. After 1.5 years, the wound was fully closed, and he could walk with the help of a walking stick. Treatment for multiple exposed bones, tendons, and muscles in uncontrolled T2DM patient are complex. Studies reported that Indonesian honey could provide an antibacterial effect, cost-efficiency, speed up wound healing with no side effects, and no physical-chemical properties differences compared to Manuka honey. Using Indonesian randu honey as wound dressing could stimulate wound healing with no side effects in chronic wounds with uncontrolled T2DM that were supposed to be amputated. However, it took several months for the wound to fully close.


Three different bacterial detection systems for platelet concentrates under inter-laboratory conditions.
A variety of screening methods are currently used worldwide in order to decrease the risk of transfusion-transmitted sepsis and improve the safety of PCs. PCs inoculated with five different transfusion-relevant species of bacteria at concentrations of 1, 10, and 100 colony-forming units (CFU)ml(-1) were stored at 22°C for 7 days. Flow cytometry (FACS), BacT/Alert automated culturing, and a quantitative real-time PCR (Q-PCR) were then used to detect the presence of bacteria in samples prepared from these PCs. At the initial spiking concentrations of 1, 10, and 100 CFU ml(-1), Q-PCR detected all five bacterial species tested. Screening with the BacT/Alert culture-based system allowed bacterial detection (inoculated on day 0) within a mean time of 15.13 h for all three spiking concentrations. Using FACS, positive signals were obtained for all three concentrations of Escherichia coli and Bacillus cereus on day 1 and for initial spiking concentrations of Pseudomonas aeruginosa and Staphylococcus aureus of 1 CFU ml(-1) on day 2. For Staphylococcus epidermidis, detection of an initial inoculum of 1 CFU ml(-1) was possible only beginning on day 6. This study shows that under standard laboratory conditions the sensitivity of FACS in the detection of bacterial contamination of PCs was lower than that of either the BacT/Alert automated culturing method or Q-PCR.


Enantioselective Bioaccumulation of the Chiral Insecticide Indoxacarb in Zebrafish (Danio rerio).
Indoxacarb is a typical chiral insecticide widely used in agricultural pest control. In the present study, zebrafish was used as a model animal to explore the enantioselective bioaccumulation behavior of indoxacarb to nontarget species in aquatic environments. Zebrafish were exposed to 0.025 and 0.1 mg/L rac-indoxacarb solution for 12 d under the semistatic method, and the bioconcentration factor (BCF) and enantiomeric fraction of zebrafish were investigated. The results showed that the (-)-R-indoxacarb preferentially accumulated in zebrafish. The BCF values at 0.025 mg/L exposure levels were 1079.8 and 83.4 L/kg for (-)-R-indoxacarb and (+)-S-indoxacarb after 12 d, respectively. The BCF values at 0.1 mg/L exposure levels were 1752.1 and 137.0 L/kg for (-)-R-indoxacarb and (+)-S-indoxacarb after 10 d, respectively. The half-life values of (-)-R-indoxacarb and (+)-S-indoxacarb were 3.47 and 2.05 d for 0.025 mg/L concentration exposure and 4.95 and 2.66 d for 0.1 mg/L concentration exposure, respectively. The enantiomeric fraction values were in the range of 0.48 to 0.55 and 0.89 to 1.00 for water and zebrafish samples, respectively. Studies on the enantioselective bioaccumulation behavior of indoxacarb will provide data for assessing the environmental fate and potential toxic effects of indoxacarb on aquatic organisms. Environ Toxicol Chem 2021;40:1007-1016. © 2020 SETAC.


Cerebrospinal fluid.
It is hoped that we have demonstrated that collection, handling, and limited analysis of CSF samples from the dog and cat are relatively simple. No special equipment or handling is required, and the procedures are within the capabilities of any veterinarian interested in performing them. In addition, although this article was not intended to present a detailed discussion on the interpretation of the analysis of CSF, we have demonstrated some very practical interpretations to the various aspects of a routine CSF analysis. When combined with a signalment, complete history, and thorough general physical and neurologic examination, CSF analysis can prove invaluable in the workup of an animal with a neurologic disorder. Relatively simple laboratory procedures can be helpful in differentiating peripheral blood contamination from true intrathecal hemorrhage, in identifying an active inflammatory process, in potentially characterizing an etiologic agent, and, on rare occasions, in identifying primary or metastatic neoplastic disease involving the CNS. In many cases, the above is not directly possible, because the changes observed in our routine analysis are nonspecific. Yet, documenting and following these "nonspecific" alterations are helpful in determining if there is progression or regression of the disease process. In turn, these changes or lack of changes are helpful in identifying if the proper therapy has been instituted and if additional or different therapy is required.


Head-to-head comparison of the diagnostic performance of coronary computed tomography angiography and dobutamine-stress echocardiography in the evaluation of acute chest pain with normal ECG findings and negative troponin tests: A prospective multicenter study.
To perform a head-to-head comparison of coronary CT angiography (CCTA) and dobutamine-stress echocardiography (DSE) in patients presenting recent chest pain when troponin and ECG are negative. Two hundred seventeen patients with recent chest pain, normal ECG findings, and negative troponin were prospectively included in this multicenter study and were scheduled for CCTA and DSE. Invasive coronary angiography (ICA), was performed in patients when either DSE or CCTA was considered positive or when both were non-contributive or in case of recurrent chest pain during 6month follow-up. The presence of coronary artery stenosis was defined as a luminal obstruction >50% diameter in any coronary segment at ICA. ICA was performed in 75 (34.6%) patients. Coronary artery stenosis was identified in 37 (17%) patients. For CCTA, the sensitivity was 96.9% (95% CI 83.4-99.9), specificity 48.3% (29.4-67.5), positive likelihood ratio 2.06 (95% CI 1.36-3.11), and negative likelihood ratio 0.07 (95% CI 0.01-0.52). The sensitivity of DSE was 51.6% (95% CI 33.1-69.9), specificity 46.7% (28.3-65.7), positive likelihood ratio 1.03 (95% CI 0.62-1.72), and negative likelihood ratio 1.10 (95% CI 0.63-1.93). The CCTA: DSE ratio of true-positive and false-positive rates was 1.70 (95% CI 1.65-1.75) and 1.00 (95% CI 0.91-1.09), respectively, when non-contributive CCTA and DSE were both considered positive. Only one missed acute coronary syndrome was observed at six months. CCTA has higher diagnostic performance than DSE in the evaluation of patients with recent chest pain, normal ECG findings, and negative troponine to exclude coronary artery disease.


Stability analysis and control technology of the sump-surrounding rock under a 1200-m-deep goaf: a case study.
In this study, a sump in the Xingdong coal mine (buried at a depth of over 1200 m) was used to analyze the surrounding rock's stability and control technology. Under the combined influences of various complex conditions, such as the burial depth of over 1200 m, ultra-high ground stress, and location under the goaf, the sump support became extremely difficult, severely restricting the efficient production of the mine. The overall pressure-relief mechanisms and degree of the sump surrounding the rock environment under the goaf were studied, and the rationality of the sump location was verified through numerical simulations and field tests. A more effective support scheme was proposed based on the deformation characteristics and failure mechanisms of the temporary sump-surrounding rock under the supporting conditions. The combined control technology employed the lengthened strong anchor bolts (cables), full-section concrete-filled steel tubular supports, and pouring full-section reinforced concrete and full-section long-hole grouting reinforcement. The field test results showed that after adopting the new support scheme, the sump-surrounding rock tended to be stable after three months. The sump roof subsidence amount, floor heave amount, and convergence of the two sidewalls of the sump were 17.2-19.2 mm, 13.9-16.5 mm, and 23.2-27.9 mm, respectively, thus satisfying the application requirements. This study provides an essential reference for deep-mine roadway support under a complex high-ground-stress environment.


Spontaneous closure of ductus arteriosus in interrupted aortic arch with ventricular septal defect.
A 2-month-old boy diagnosed with interrupted aortic arch type B was treated with a two-stage procedure. His ductus arteriosus had closed spontaneously. Collaterals via both vertebral arteries developed. A 15-mm stenotic segment existed between the left subclavian artery and the descending aorta. The direct anastomosis between the common carotid artery and the descending aorta was performed as a first palliation at the age of 3 months. The left subclavian artery was reconstructed by end-to-side anastomosis to the descending aorta. The postoperative course was uneventful. The closure of ventricular septal defect and pulmonary artery debanding were performed as a second operation 4 months after the first palliation. The patient is alive and well 7 months after the second operation.


Verb finding in aphasia.
Word finding for nouns and verbs was examined in a heterogeneous group of aphasics (N = 9) by comparing the ability to generate synonyms and sentences for the same set of 20 nouns and 20 verbs. Synonym Generation performance resembled that of an age-matched group of normal control subjects (n = 9): In both groups, some subjects produced comparable numbers of synonyms for nouns and verbs while other subjects produced significantly fewer synonyms for verbs. Essentially the same two patterns were displayed on Sentence Generation using the frequency of "empty" nouns (e.g., 'it', 'man') and "empty" verbs (e.g., 'is', 'do') as an index of word-finding difficulty: In both groups, some subjects produced comparable numbers of empty nouns and verbs, while other subjects produced significantly more empty verbs. However, the Sentence Generation performance of one aphasic subject stood out overall by her tendency to avoid empty verbs and produce incomplete sentences. This pattern of performance was interpreted as a breakdown in an early stage of sentence planning that may be directly related to her diagnosis of transcortical motor aphasia.


Ontario appellate court denies HIV-positive man's constitutional claim to medical marijuana.
In January 2002, the Ontario Court of Appeal denied a claim by a Toronto man living with HIV/AIDS that Canada's laws prohibiting marijuana possession and cultivation infringe his constitutional rights to liberty and security of the person.


Proton magnetic resonance spectroscopy of leech muscle and nervous system.
1. Proton nuclear magnetic resonance spectroscopy (1H NMR) was used to measure the major intracellular metabolites in perchloric acid extracts of the Macrobdella decora muscle and nervous systems and the Oryctolagus cuniculus cerebrum. 2. Acetate, alanine, choline, glutamate, inositol, and lactate were assigned in the spectrum of leech ventral cord, leech muscle, and rabbit cerebrum. 3. Hirudonine and propionate were clearly observed only in the spectrum of leech muscle. 4. Creatine, N-acetyl aspartate, gamma aminobutyric acid, aspartate, and taurine, distinctive components of spectra of the mammalian cerebrum, were not seen in the invertebrate spectra. 5. 1H NMR spectroscopy provides a simple and rapid means of characterizing the major organic metabolites found in leech muscle and nervous tissues.


An in vitro 3D annulus fibrosus cell culture model with type I collagen: An examination of cell-matrix interactions.
Disorders of the intervertebral disc (IVD) are widely known to result in low back pain; one of the most common debilitating conditions worldwide. As a multifaceted condition, both inflammatory environment and mechanical factors can play a crucial role in IVD damage, and in particular, in the annulus fibrosus (AF), the highly collagenous outer ring of the IVD. As a result, a better understanding of how cells from the IVD, and specifically the AF, interact and respond to their environment is imperative. The goal of this study is to use collagen type I as an in vitro three-dimensional extracellular matrix for AF cells of IVD and briefly examine both the cellular and mechanical effect of exposure to an inflammatory stimulant. We utilized type I collagen as a 3D in vitro model material for culturing AF cells of Sprague Dawley rat tail IVDs. We showed that the cultured cells are viable and metabolically active; these cells also induced a distinct and significant contraction on their collagen matrix. Furthermore, to demonstrate potential versatility of our model our model and its versatility, we used lipopolysaccharide (LPS), as a known inflammatory stimulant in IVDs, to manipulate the cells and their interaction. LPS treatment resulted in detectable changes to the contraction cells induced on the collagen matrix and affected the mechanical properties of these constructs.


[Arthroscopic tightening of the anterior cruciate ligament].
We present here the preliminary results obtained with arthroscopic tightening of the anterior cruciate ligament. Six patients underwent the technique. Four had had prior ligamentoplasty, two had sequelae of tibial spine fractures. Laxity persisted in all cases. The transplant or the ligament were continuous and insertion points were well-positioned. The procedure consisted in using a trephine to bore the tibial bone at the "foot" of the ligament or transplant in order to tighten the ligament. There was no evidence of instability after the arthroscopic tightening procedure. Mean pre- and postoperative differential anterior drawer values were successively 9.2 and 3.9 mm. For native or reconstructed anterior cruciate ligaments, which are continuous and well-positioned but not loose, arthroscopic tightening spares the need for ligament transplant and appears to be free of specific morbidity.


Dataset for chemorheological and rheokinetic analysis of carbohydrate-HMF-amine adhesives.
The work consists of primary and analysed data from rheological measurements of carbohydrate-hydroxymethylfurfural-amine adhesives. The studied adhesives are a bio-based alternative to conventional wood adhesives. The rheological properties were studied at different temperatures in isothermal (80, 90, 95 °C) and non-isothermal (20-120 °C) oscillatory measurements. Non-isothermal rheological measurements were used for the determination of the activation energy based on Vyazovskin's isoconversional method. The viscosity profile of the adhesives, determined from isothermal measurements, was fitted by an empirical model. The viscosity kinetic constant can be obtained from this empirical model and used in further rheokinetic analysis. Data from density and swelling experiments was measured for the characterization of the adhesive network. The determined polymer-solvent interaction parameter is included in the collected data. The provided datasets were used in the investigation of the reactivity and curing reaction of the studied adhesives. A discussion and interpretation of the data can be found in the previous publication [1].


Correction: A Mobile App (FallSA) to Identify Fall Risk Among Malaysian Community-Dwelling Older Persons: Development and Validation Study.
[This corrects the article DOI: 10.2196/23663.].


Women's perspectives are required to inform the development of maternal obesity services: a qualitative study of obese pregnant women's experiences.
Increasing maternal obesity trends and accompanying risks have led to the development of guidelines internationally. However, the evidence-base is poor for effective intervention, and there is a lack of representation from the perspective of obese pregnant women in guidelines. Women's engagement with weight management support services is low. To explore obese pregnant women's experiences to better understand factors which need to be considered when developing services that women will find acceptable and utilize. Obese women referred to an antenatal dietetic service in the Northeast of England, UK. Low-structured depth-interviews allowed women to freely discuss their own experiences. Discussion prompts were included; however, issues that women raised were explored thoroughly. Women summarized what they considered most important to ensure the analyses placed appropriate emphasis on factors women perceived as important. Thematic analysis identified common themes. Saturation was confirmed after 15 interviews. Key issues included: women's weight; families; experience of negativity; and priorities and desired outcomes. These combined represented women's perspectives of issues which they considered important and integral to their lived experience of being obese and pregnant. The theme incorporates women's pregnancy-related experiences, as well as life experiences which contributed to how they felt about their weight during pregnancy. There are strong associations with women's lived experiences and engagement with antenatal weight management services. Incorporating women's perspectives in the development of these services could encourage engagement by focussing on women's priorities and motivations, while taking into consideration their socially related experiences in addition to their clinical health needs.


Relaxation training affects success and activation on a teaching test.
We studied the effects of an audiocassette-relaxation training period (ART) and its timing on success at a teaching test (lecture type), on observed tension and on a number of physiological responses. The electrical activity of the upper trapezius muscle (EMG), heart rate (HR) and blood pressure (BP), of female and male instructor candidates, were examined before, during and after the teaching test as well as during its critique. The relaxation period (18 min) was presented either on the preceding night (ARTnt) or immediately before the teaching test (ARTimm). The influence of personality (types A-B and extrovert-introvert) was also studied. ART improved success at the teaching test in both sexes. In males (but not in females), ARTimm decreased EMG level during the test, but ARTnt increased EMG at the test period as compared to the control group. In females, both ARTnt and ARTimm lowered HR more than in the control group. ARTimm lowered systolic BP in both sexes. Personality types affected the ART responses; ART was more beneficial for type A than B subjects.