Efficient hysteresis-less bilayer type CH₃NH₃PbI₃ perovskite hybrid solar cells.
Bilayer type CH3NH3PbI3 (MAPbI3) perovskite hybrid solar cells were fabricated via a one-step spin-coating process by using solubility controlled MAPbI3 solutions of MAPbI3-DMSO (dimethyl sulfoxide) and MAPbI3-DMF (N, N-dimethylformamide)-HI. The best DMSO-bilayer device showed 1.07 ± 0.02 V V(oc) (open-circuit voltage), 20.2 ± 0.1 mA cm(-2) J(sc) (short-circuit current density), 68 ± 2% FF (fill factor), and 15.2 ± 0.3% η (overall power conversion efficiency) under the forward scan direction and 1.07 ± 0.02 V V(oc), 20.4 ± 0.1 mA cm(-2) J(sc), 70 ± 3% FF, and 15.9 ± 0.4% η under the reverse scan direction. The best HI-bilayer device had 1.08 ± 0.02 V V(oc), 20.6 ± 0.1 mA cm(-2) J(sc), 75 ± 1% FF, and 17.2 ± 0.2% η under the forward scan direction and 1.08 ± 0.02 V V(oc), 20.6 ± 0.1 mA cm(-2) J(sc), 76 ± 2% FF, and 17.4 ± 0.3% η under the reverse scan direction. The deviation of average device efficiency (η(avg)) of 20 DMSO samples and 20 HI samples was 14.2 ± 0.95% and 16.2 ± 0.85%, respectively. Therefore, the HI-bilayer devices exhibited better device efficiency and smaller J-V (current density-voltage) hysteresis with respect to the scan direction than the DMSO-bilayer devices due to the reduced recombination and traps by the formation of a purer and larger MAPbI3 perovskite crystalline film.


Relevance of the pyroptosis-related inflammasome drug targets in the Chuanxiong to improve diabetic nephropathy.
A chronic inflammatory disease caused by disturbances in metabolism, diabetic nephropathy (DN) is a chronic inflammatory disease. Pyroptosis is a novel form of programmed cell death in many inflammation-related diseases, including DN. Therefore, pyroptosis could be a promising target for DN therapy. To get the components and pharmacodynamic targets of Chuanxiong, we identified by searching TCMID, TCMSP, ETCM and HERB databases. Then, from the Molecular Signatures Database (MSigDB) and Gene Ontology (GO) database, pyroptosis genes were collected. Identification of critical genes in DN by bioinformatics analysis and then using the ConsensusClusterPlus package to divide the express data of diff genes into some subgroups with different levels of pyroptosis; the WGCNA machine algorithm was used to simulate the mechanism Chuanxiong improving DN. In this study, we found DHCR24, ANXA1, HMOX1, CDH13, ALDH1A1, LTF, CHI3L1, CACNB2, and MTHFD2 interacted with the diff genes of DN. We used GSE96804 as a validation set to evaluate the changes of APIP, CASP6, CHMP2B, CYCS, DPP8, and TP53 in four different cell proapoptotic states. WGCNA analysis showed that DHCR24, CHI3L1, and CACNB2 had significant changes in different cell proapoptotic levels. In the experimental stage, we also confirmed that the active ingredients of Chuanxiong could improve the inflammatory state and the levels of pyroptosis under high glucose. The improvement of DN by Chuanxiong is related to the change of pyroptosis.


Diabetes and incidence of breast cancer and its molecular subtypes: A systematic review and meta-analysis.
Diabetes mellitus (DM) has been proposed to be positively associated with breast cancer (BCa) risk due to shared risk factors, metabolic dysfunction, and the use of antidiabetic medications. We conducted a systematic review and meta-analysis to evaluate the association between DM and BCa risk. We searched PubMed, Embase, and Web of Science for cohort and case-control studies assessing the association between DM and BCa published before 10 December 2021. Two reviewers independently screened the studies for inclusion, abstracted article data, and rated study quality. Random effects models were used to estimate summary risk ratios (RRs) and 95% confidence intervals (CIs). From 8396 articles identified in the initial search, 70 independent studies were included in the meta-analysis. DM was associated with an overall increased risk of BCa (RR = 1.20, 95% CI: 1.11-1.29). The 24 case-control studies demonstrated a stronger association (RR = 1.26, 95% CI: 1.13-1.40) than the 46 cohort studies (RR = 1.15, 95% CI: 1.05-1.27). Studies reporting risk by menopausal status found that postmenopausal women had an elevated risk of developing BCa (RR = 1.12, 95% CI: 1.07-1.17). No association between DM and BCa risk was observed among premenopausal women (RR = 0.95, 95% CI: 0.85-1.05). In addition, DM was associated with significantly increased risks of oestrogen receptor (ER)+ (RR = 1.09, 95% CI: 1.00-1.20), ER- (RR = 1.16, 95% CI: 1.04-1.30), and triple negative BCa (RR = 1.41, 95% CI: 1.01-1.96). The association estimate for human epidermal growth factor 2-positive BCa was also positive (RR = 1.21, 95% CI: 0.52-2.82), but the CI was wide and crossed the null. Our meta-analysis confirms a modest positive association between DM and BCa risk. In addition, our results suggest that the association between DM and BCa may be modified by menopausal status, and that DM may be differentially associated with BCa subtypes defined by receptor status. Additional studies are warranted to investigate the mechanisms underlying these associations and any influence of DM on BCa receptor expression.


Comparison of resource utilization in the treatment of open-angle glaucoma between two cities in Finland: is more better?
Glaucoma is a progressive optic neuropathy associated with neural rim loss of the optic disc and the retinal nerve fibre layer typically causing visual field (VF) deterioration. Generally, glaucomatous lesions in the eye and in the visual field progress slowly over the years. In population-based cross-sectional studies, the percentage of unilateral or bilateral visual impairment varied between 3-12%. In screening studies, 0.03-2.4% of patients have been found to suffer visual impairment. Glaucoma has previously been associated with substantial healthcare costs and resource consumption attributable to the treatment of the disease. The disease also causes reduction in health-related quality of life (HRQoL) in patients with glaucoma. This study compares patients with diagnosed open-angle glaucoma from two geographically different regions in Finland. A total of 168 patients were examined, 85 subjects from an area with higher per patient treatment costs (Oulu) and 83 patients from a region with lower per patient treatment costs (Turku). All patients had a history of continuous glaucoma medication use for a period of 11 years. For each patient, the total direct costs from glaucoma treatment were calculated and the total amount of resource consumption was determined from registries and patient records. Each patient underwent a clinical examination with visual field assessment and fundus photography. These data were used to determine the current stage of disease for each patient. Health-related quality of life questionnaire (15D) was used in determining each patient's subjective HRQoL score. When applying the current diagnostic criteria for open-angle glaucoma, a total of 40% of patients did not to display any structural or functional damage suggesting glaucoma after 11 years of continuous medical treatment and follow-up. Patients with higher glaucoma stage (worse disease) were found to have statistically higher treatment costs compared with those at lower disease stages. Resource consumption was also greater in the patients in higher glaucoma stage. Patients in the Oulu district consumed more resources, and glaucoma treatment was more expensive than in the Turku area. The total treatment cost in Oulu and Turku was 6010 € and 4452 €, respectively, for the whole 11-year period. There was no statistically significant difference in quality-of-life scores between the two areas. No difference was noted between the higher-spending and lower-spending areas in this respect. However, when the population was analysed as a whole, patients with higher glaucoma stage were found to have lower vision-based 15D scores compared with those at lower disease stages. This observation was made also at both districts independently. Major cost source in open-angle glaucoma treatment is medication, up to 74% of annual costs. In addition, it seems that higher resource consumption and higher treatment costs do not increase the patients' HRQoL as assessed by the 15D instrument.


Role of fine needle aspiration cytology in diagnosis of pleomorphic adenomas.
This retrospective study was carried out to review the cases diagnosed as pleomorphic adenoma in major or minor salivary glands and determine the difficulties encountered on typing this tumour on fine needle aspiration cytology (FNAC). Over a 19-year period (1982-2000) 488 pleomorphic adenomas were diagnosed on FNAC from different sites (parotid - 372 cases, submandibular - 95 cases; oral cavity - 21 cases). Histology was available in 232 cases. Twenty-nine cases where a histological diagnosis of pleomorphic adenoma was made but the cytological diagnosis was variable were also reviewed. In 216 of the 232 cases a good cytohistological correlation was available. On review only 4 of the 16 cases initially diagnosed as pleomorphic adenoma on FNAC where the histology revealed a different tumour were categorized as pleomorphic adenoma, while 3 each were classified as adenoid cystic carcinoma and benign tumour ?type, and 2 each were diagnosed to be muco-epidermoid carcinoma, monomorphic adenoma and acinic cell carcinoma. On review of the FNAC smears from 29 cases where a histological diagnosis of pleomorphic adenoma was available while the cytological diagnosis was variable, only 11 (38%) were categorized as pleomorphic adenoma. In the majority of the remaining cases the cytological diagnosis did not alter markedly, 7 of 10 cases where the tumour could not be typed on cytology initially could not be typed even on review. In conclusion, FNAC is an ideal, fairly accurate preoperative procedure for the diagnosis of pleomorphic adenomas. Certain diagnostic problems occur in differentiating pleomorphic adenomas from adenoid cystic carcinoma, monomorphic adenoma and mucoepidermoid carcinoma. Carcinoma ex-pleomorphic adenoma is difficult to identify on FNAC and in our series all 4 such cases on histology were considered benign on cytology.


RhANP attenuates endotoxin-derived cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota-brain axis.
Atrial natriuretic peptide (ANP) secreted from atrial myocytes is shown to possess anti-inflammatory, anti-oxidant and immunomodulatory effects. The aim of this study is to assess the effect of ANP on bacterial lipopolysaccharide (LPS)-induced endotoxemia-derived neuroinflammation and cognitive impairment. LPS (5 mg/kg) was given intraperitoneally to mice. Recombinant human ANP (rhANP) (1.0 mg/kg) was injected intravenously 24 h before and/or 10 min after LPS injection. Subdiaphragmatic vagotomy (SDV) was performed 14 days before LPS injection or 28 days before fecal microbiota transplantation (FMT). ANA-12 (0.5 mg/kg) was administrated intraperitoneally 30 min prior to rhANP treatment. LPS (5.0 mg/kg) induced remarkable splenomegaly and an increase in the plasma cytokines at 24 h after LPS injection. There were positive correlations between spleen weight and plasma cytokines levels. LPS also led to increased protein levels of ionized calcium-binding adaptor molecule (iba)-1, cytokines and inducible nitric oxide synthase (iNOS) in the hippocampus. LPS impaired the natural and learned behavior, as demonstrated by an increase in the latency to eat the food in the buried food test and a decrease in the number of entries and duration in the novel arm in the Y maze test. Combined prophylactic and therapeutic treatment with rhANP reversed LPS-induced splenomegaly, hippocampal and peripheral inflammation as well as cognitive impairment. However, rhANP could not further enhance the protective effects of SDV on hippocampal and peripheral inflammation. We further found that PGF mice transplanted with fecal bacteria from rhANP-treated endotoxemia mice alleviated the decreased protein levels of hippocampal polyclonal phosphorylated tyrosine kinase receptor B (p-TrkB), brain-derived neurotrophic factor (BDNF) and cognitive impairment, which was abolished by SDV. Moreover, TrkB/BDNF signaling inhibitor ANA-12 abolished the improving effects of rhANP on LPS-induced cognitive impairment. Our results suggest that rhANP could mitigate LPS-induced hippocampal inflammation and cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota-brain axis.


CT angiography for the management of postpartum hemorrhage refractory to conservative treatment.
Postpartum hemorrhage (PPH) is one of the leading causes of maternal morbidity and mortality. Computerized tomographic (CT) angiography is a useful tool to identify hemorrhage from various conditions. However, the feasibility of CT angiography for the management of PPH has not been well evaluated. To evaluate the clinical usefulness of CT angiography in the management of PPH refractory to the conservative treatment. This retrospective cohort study consisted of 528 consecutive patients who were transferred to our institute after delivery at 28 primary maternity hospitals for the management of PPH between 2009 and 2017. Immediate intervention such as arterial embolization and hysterectomy were performed on 278 patients. Of the remaining 250 patients, CT angiography was performed on 61 patients with hemodynamic stability but with sustained hemorrhage refractory to medical treatment. The diagnostic index was assessed using conventional angiography as the reference standard. The clinical outcome was compared between patients with and without contrast extravasation on CT angiography. (1) The prevalence of contrast extravasation was found in 61% of patients (37/61); (2) conventional angiography and arterial embolization were performed in 78% of patients (29/37) with contrast extravasation on CT angiography. Contrast extravasation was confirmed in 83% of patients (24/29) by conventional angiography; (3) among the 24 patients without contrast extravasation on CT angiography, 96% (23/24) were managed conservatively; (4) the patients with contrast extravasation on CT angiography received more packed red blood cell (PRBC) transfusion than those without that condition (7.3 ± 5.2 units vs. 3.8 ± 2.9 units, p = .009). Massive transfusion (defined as transfusion of 10 or more units of PRBC) was more common in patients with contrast extravasation than in those without (27% [10/37] vs. 0% [0/24], p = .004). Conservative treatment succeeded in 96% of patients without contrast extravasation on CT angiography. CT angiography is useful to identify patients requiring intervention in the management of hemorrhage refractory to medical treatment.


Modulation of mRNA Expression of Monoacylglycerol Lipase, Diacylglycerol Lipase and Cannabinoid Receptor-1 in Mice Experimentally Infected with T. gondii.
Toxoplasma gondii, an obligate intracellular parasite, infects more than 30% of world's population. This parasite is considered to be neurotropic, and has high tropism for the central nervous system, and potentially induces cryptogenic epilepsy by no clear mechanism. The current study aimed to investigate the alteration of the main components of the endocannabinoid signaling systems in T. gondii-infected mice. For this purpose, the levels of mRNA expression of monoacylglycerol lipase (MAGL), diacylglycerol lipase (DAGL) and cannabinoid receptor-1 (CB1), were measured by quantitative real time PCR.The mRNA expression level of MAGL was increased by ~ 8-fold in the brains of the Toxoplasma-infected group in comparison with non-infected mice (P<0.0001). The mRNA expression of CB1 gene in the brain of the infected mice was ~ 2 times higher than that measured in control group (P<0.01). The mRNA expression level of DAGL remained unchanged in the infected mice. Overall a substantial increase in MAGL and CB1 expression without any changes in DAGL, in the brain of infected mice suggests that T. gondii disturbs the endocannabinoid signaling pathways, which are known as neurotransmitter modulators involved in epilepsy.


Administering a two-stage spiritual assessment in healthcare settings: a necessary component of ethical and effective care.
This article delineates rationales for administering a spiritual assessment as a universal component of care. The notion that nurses should identify and address patients' spiritual needs remains controversial, particularly in the UK where criticisms derived from secularization theory have appeared in the literature. To respond to these criticisms and to develop rationales supportive of spiritual assessment, I draw upon scholarship from a variety of disciplines including social work, sociology, and medicine. Five rationales are posited to support the concept of universal spiritual assessments: professional ethics, patient autonomy, knowledge of patients' worldviews, the identification of spiritual assets, and accrediting and governmental requirements. Criticisms based on secularization theory are discussed and analysed. A two-stage spiritual assessment - consisting of a brief preliminary assessment followed, if necessary, by a comprehensive assessment - provides a mechanism to efficiently identify patients' spiritual needs. As key members of the healthcare team, nurse managers are ideally situated to ensure that all patients receive a spiritual assessment as a routine component of care. In so doing, they help ensure the provision of ethical and effective care to the diverse spiritual groups that will continue to populate the UK for the foreseeable future.


A case of encapsulated papillary carcinoma of the breast treated with emergency surgery due to sudden hemorrhage.
Emergency surgery is rare in management of breast cancer. We report a case of encapsulated papillary carcinoma (EPC) of the breast where emergency surgery was performed because of unsuccessful control of hemorrhage. A 62-year-old woman visited our hospital complaining of sudden bleeding from the right breast. She had been aware of the tumor for a year, but had left it unattended. It had been increasing in size rapidly for a few days before presentation. Computed tomography showed a hypervascular cystic tumor 9 cm in diameter. Bleeding was observed from a skin breach in the right breast, from which a clot was removed and the wound compressed with gauze. We attempted unsuccessfully to control the hemorrhage over the next 3 days, but the patient became anemic, so emergency surgery was performed to control the bleeding. Histopathology revealed the tumor as estrogen receptor- and progesterone receptor-positive EPC, with a human epidermal growth factor receptor 2 score of 0. There have been only 5 reports of breast cancer treated with emergency surgery. EPC was previously considered an in situ lesion, but the lack of a myoepithelial layer at the lesion's periphery may represent a low grade or indolent form of invasive carcinoma and prognosis is usually good. However, if bleeding into the cyst occurs and hemostasis is difficult, emergency surgery should be considered. Emergency surgery is rare in breast cancer but should always be considered as an option when hemorrhage is not readily controlled.


Erratum: Subcellular Organelle-Targeted Nanostructured Lipid Carriers for the Treatment of Metastatic Breast Cancer [Corrigendum].
[This corrects the article DOI: 10.2147/IJN.S413680.].


Non disseminative nano-strategy against in vivo Staphylococcus aureus biofilms.
Staphylococcus aureus is considered a high priority pathogen by the World Health Organization due to its high prevalence and the potential to form biofilms. Currently, the available treatments for S. aureus biofilm-associated infections do not target the extracellular polymeric substances (EPS) matrix. This matrix is a physical barrier to bactericidal agents, contributing to the increase of antimicrobial tolerance. The present work proposes the development of lipid nanoparticles encapsulating caspofungin (CAS) as a matrix-disruptive nanosystem. The nanoparticles were functionalized with D-amino acids to target the matrix. In a multi-target nano-strategy against S. aureus biofilms, CAS-loaded nanoparticles were combined with a moxifloxacin-loaded nanosystem, as an adjuvant to promote the EPS matrix disruption. In vitro and in vivo studies showed biofilm reduction after combining the two nanosystems. Besides, the combinatory therapy showed no signs of bacterial dissemination into vital organs of mice, while dissemination was observed for the treatment with the free compounds. Additionally, the in vivo biodistribution of the two nanosystems revealed their potential to reach and accumulate in the biofilm region, after intraperitoneal administration. Thus, this nano-strategy based on the encapsulation of matrix-disruptive and antibacterial agents is a promising approach to fight S. aureus biofilms.


Analysis of Cell Cycle Status of Murine Hematopoietic Stem Cells.
Hematopoietic stem cells (HSC) act as paradigmatic tissue-specific adult stem cells. While they are quiescent in steady-state conditions, they enter the cell cycle and proliferate in stress conditions and during tissue regeneration. Therefore, analysis of cell cycle status of HSC is crucial for understanding their biology. However, due to low number of HSC in tissue and need to use many surface markers for their identification, analysis of their cycle status is technically complicated. Here, we presented our simple strategy to analyze cell cycle of strictly defined LKS CD48(-)CD150(+)CD34(-) HSC, together with Ki67 and DAPI staining by flow cytometry.


An accurate electrocardiographic algorithm for differentiation of tremor-induced pseudo-ventricular tachycardia and true ventricular tachycardia.
Tremor-induced electrocardiographic artifacts could be misdiagnosed as ventricular tachycardia (VT). However, there has been no electrocardiographic algorithm effectively differentiating pseudo-VT. In this study, we used 3 electrocardiographic "signs": "Sinus" sign, "Spike" sign, and "Notch" sign, and created an electrocardiographic algorithm. The algorithm was prospectively tested in 98 electrocardiographs (37 tremor-induced pseudo-VT and 61 true VT) Thirty-six out of 37 (97.3%) tremor-induced pseudo-VTs could be accurately diagnosed. In conclusion, this is the first study to systemically analyze the tremor-induced pseudo-VT. Our new electrocardiographic algorithm provides a useful tool for a rapid and accurate diagnosis.


Key role of receptor density in colloid/cell specific interaction: a quantitative biomimetic study on giant vesicles.
This paper presents an experimental study of the adsorption of colloids on model membranes mediated by specific ligand-receptor interactions. The colloids consist of lipid multilamellar liposomes (spherulites) functionalized with the B-subunit of Shiga Toxin (STxB), while the membranes are lipid Giant Unilamellar Vesicles (GUV) containing STxB lipid receptor, Globotriaosylceramide (Gb3). Through confocal microscopy and flow cytometry, we show the specificity of the adsorption. Moreover, we show that flow cytometry can be used to efficiently quantify the kinetics of colloid adsorption on GUVs with very good statistics. By varying the bulk colloid concentration and receptor density in the membrane, we point out the existence of an optimum Gb3 density for adsorption. We propose that this optimum corresponds to a transition between reversible colloid adsorption at low Gb3 density and irreversible adsorption, and likely spherulite fusion, at high density. We compare our results both to STxB-colloids adhering on living cells and to free STxB proteins interacting with GUVs containing Gb3. This biomimetic system could be used for a quantitative evaluation of the early stage of virus infection or drug delivery.


Bridging the gap between batch and column experiments: A case study of Cs adsorption on granite.
Both batch and column methods are conventionally utilized to determine some critical parameters for assessing the transport of contaminants of concern. The validity of using these parameters is somewhat confusing, however, since outputs such as distribution coefficient (Kd) from these two approaches are often discrepant. To bridge this gap, all possible factors that might contribute to this discrepancy were thoroughly investigated in this report by a case study of Cs sorption to crushed granite under various conditions. Our results confirm an important finding that solid/liquid (S/L) ratio is the dominant factor responsible for this discrepancy. As long as the S/L ratio exceeds 0.25, a consistent Kd value can be reached by the two methods. Under these conditions (S/L ratios>0.25), the sorption capacity of the solid is about an order of magnitude less than that in low S/L ratios (<0.25). Although low sorption capacity is observed in the cases of high S/L ratios, the sorption usually takes place preferentially on the most favorable (thermodynamically stable) sorption sites to form a stronger binding. This is verified by our desorption experiments in which a linear isotherm feature is shown either in deionized water or in 1M of ammonium acetate solutions. It may be concluded that batch experiment with an S/L ratio exceeding 0.25 is crucial to obtain convincing Kd values for safety assessment of radioactive waste repository.


Robust one-tube Ω-PCR strategy accelerates precise sequence modification of plasmids for functional genomics.
Functional genomics requires vector construction for protein expression and functional characterization of target genes; therefore, a simple, flexible and low-cost molecular manipulation strategy will be highly advantageous for genomics approaches. Here, we describe a Ω-PCR strategy that enables multiple types of sequence modification, including precise insertion, deletion and substitution, in any position of a circular plasmid. Ω-PCR is based on an overlap extension site-directed mutagenesis technique, and is named for its characteristic Ω-shaped secondary structure during PCR. Ω-PCR can be performed either in two steps, or in one tube in combination with exonuclease I treatment. These strategies have wide applications for protein engineering, gene function analysis and in vitro gene splicing.


The PSG challenge: towards comprehensive scene understanding.
The Panoptic Scene Graph Generation (PSG) challenge evaluates computer vision models to identify relations in images beyond object classification and localization, enabling a deeper understanding of scenes for real-world AI applications.


Polyoxygenated cinnamoylcoumarins as conformationally constrained analogs of cytotoxic diarylpentanoids: synthesis and biological activity.
A series of polyoxygenated cinnamoylcoumarins was synthesized as conformationally constrained analogs of cytotoxic diarylpentanoids. The title compounds were tested against the viability of human chronic myelogenous leukemia (K562), human acute lymphoblastic leukemia (MOLT-4) and human breast adenocarcinoma (MCF-7) cell lines by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Among them, all 6- or 7-hydroxylated compounds 6a-h exhibited remarkable cytotoxic activity. Particularly, 7-hydroxycoumarin analog 6h showed good antiproliferative activity against all tested cell lines (IC50 values≤5.5 μM). The preliminary study with selected compounds 6e and 6f showed that reactivity towards mitochondrial thiol compounds cab be considered as cytotoxic mechanism of designed compounds. Furthermore, the antioxidant activity evaluation of synthesized compounds showed that hydroxylated compounds had antioxidative potential at higher concentrations.


Electrical switching in a magnetically intercalated transition metal dichalcogenide.
Advances in controlling the correlated behaviour of transition metal dichalcogenides have opened a new frontier of many-body physics in two dimensions. A field where these materials have yet to make a deep impact is antiferromagnetic spintronics-a relatively new research direction promising technologies with fast switching times, insensitivity to magnetic perturbations and reduced cross-talk1-3. Here, we present measurements on the intercalated transition metal dichalcogenide Fe1/3NbS2 that exhibits antiferromagnetic ordering below 42 K (refs. 4,5). We find that remarkably low current densities of the order of 104 A cm-2 can reorient the magnetic order, which can be detected through changes in the sample resistance, demonstrating its use as an electronically accessible antiferromagnetic switch. Fe1/3NbS2 is part of a larger family of magnetically intercalated transition metal dichalcogenides, some of which may exhibit switching at room temperature, forming a platform from which to build tuneable antiferromagnetic spintronic devices6,7.


Measuring patients' perceptions of the outcomes of treatment for early prostate cancer.
Compared with careful attention to the physical (eg, urinary, bowel, sexual) dysfunction that may follow treatment, little attention has been given to the behavioral, emotional, and interpersonal changes that the diagnosis of early prostate cancer and subsequent physical dysfunction may bring. To construct patient-centered measures of the outcomes of treatment for early prostate cancer. Qualitative study followed by survey of early prostate cancer patients and group of comparable patients with no history of prostate cancer. Analysis of focus groups identified relevant domains of quality of life, which were represented by Likert scale items included in survey questionnaires. Psychometric analyses of survey data defined scales evaluated with respect to internal consistency and validity. Qualitative analysis identified three domains: urinary control, sexuality, and uncertainty about the cancer and its treatment. Psychometric analysis defined 11 scales. Seven were generically relevant to most older men: urinary control (eg, embarrassment with leakage), sexual intimacy (eg, anxiety about completing intercourse), sexual confidence (eg, comfort with sexuality), marital affection (eg, emotional distance from spouse/partner), masculine self esteem (eg, feeling oneself a whole man), health worry (eg, apprehensiveness about health changes), and PSA concern (eg, closely attending to one's PSA). Four scales were specific to the treatment experience: perceived cancer control, quality of treatment decision making, regret of treatment choice, and cancer-related outlook. The scales provide definition and metrics for patient-centered research in this area. They complement measures of physical dysfunction and bring into resolution outcomes of treatment that have gone unnoticed in previous studies.


Disseminated clustered juvenile xanthogranuloma: an unusual morphological variant of a common condition.
Juvenile xanthogranuloma (JXG) is a benign, self-healing non-Langerhans cell histiocytosis of unknown aetiology, most commonly occurring in infants and children. JXG is characterized by solitary or multiple yellowish cutaneous nodules, the two common clinical variants being a small nodular form and large nodular form, which frequently coexist. Unusual morphological presentations include keratotic, lichenoid, pedunculated, subcutaneous, clustered, plaque-like and giant lesions. We describe the first reported case of 'disseminated' clustered juvenile xanthogranuloma presenting in an infant.


Relationship of perceptual evaluation for resonance disorders to nasalance scores in children with cleft palate.
To determine relationship between screening perceptual assessment for resonance disorders and nasalance scores. Screening perceptual assessment of 115 children with cleft palate with or without lip was performed to determine its relationship to nasalance sores. The perceptual assessment 3-scale (-1: hyponasality; 0: normal; +1: hypernasality) was compared to nasalance scores based on nasometry. To find the weight of Kappa, nasalance scores were converted to a 3-ordinal scale with 3 criteria for cut-off points (-1: nasalance score -1, -1.5 and-2 SD lower than the mean, 0: nasalance score +/- 1 SD, +/- 1.5 and +/- 2 SD of the mean; and + 1: nasalance score + 1 SD, + 1.5, and + 2 SD greater that the mean). Correlations between screening perceptual assessment and nasalance scores were good to excellent. The percentage of agreement was good, the Kappa reliability was fair to moderate in passages of a mixture of oral and nasal consonants (My House) and devoid of nasal consonants (Laying Hen). A weak relationship was found for the nasal passage (Winter). The relationship of speech assessments in the present study varied, as it depended on the different variables and analysis. To ensure a strong relationship, further prospective study is needed.


Use and misuse of serum troponin assays in pediatric practice.
Cardiac troponin (cTn) is instrumental in screening and diagnosing myocardial ischemia in adults. However, the role of cTn screening in the pediatric population is less clear. The purpose of this study was to evaluate the current clinical practice, diagnostic and prognostic value, and resource utilization associated with cTn assays in the pediatric population. A multicenter, retrospective review of all cTn assays performed on patients aged ≤18 years from January 2003 to December 2010 in the Intermountain Healthcare system was conducted. Data collected included patient demographics, location, presenting symptoms, provisional and discharge diagnoses, additional tests, clinical outcomes (hospitalization days, ventilation, and death), and patient charges. During the study period, cTn assays were performed on 3,497 pediatric patients. The most common presenting diagnoses were chest pain (40%), trauma (11%), and poisoning or drug overdose (9%). Irrespective of diagnosis, elevated cTn was associated with an increased rate of hospitalization, ventilation, and death. Overall, 12% of patients had elevated cTn. Of the patients with chest pain, 4% had elevated cTn, 53% of whom were diagnosed with myopericarditis. In the myopericarditis group, 66% presented with fever, and 98% had abnormal electrocardiographic findings. For patients presenting with chest pain, approximately $162,000 was spent per positive result. In conclusion, cTn screening has strong prognostic value in pediatric patients, even in noncardiac diagnoses such as trauma or drug overdose. However, cTn screening in pediatric patients with chest pain provides minimal benefits and is associated with increased resource utilization, unless patients have constitutional symptoms, such as fever and/or electrocardiographic abnormalities.


Non-invasive respiratory support in preterm infants.
Survival of preterm infants has increased steadily over recent decades, primarily due to improved outcomes for those born before 28 weeks of gestation. However, this has not been matched by similar improvements in longer-term morbidity. One of the key long-term sequelae of preterm birth remains bronchopulmonary dysplasia (also called chronic lung disease of prematurity), contributed primarily by the effect of early pulmonary inflammation superimposed on immature lungs. Non-invasive modes of respiratory support have been rapidly introduced providing modest success in reducing the incidence of bronchopulmonary dysplasia when compared with invasive mechanical ventilation, and improved clinical practice has been reported from population-based studies. We present a comprehensive review of the key modes of non-invasive respiratory support currently used in preterm infants, including their mechanisms of action and evidence of benefit from clinical trials.


Creating multiple time-shared laser traps with simultaneous displacement detection using digital signal processing hardware.
We present a design for implementing multiple laser traps for single-molecule studies through time-sharing using commercially available digital signal processing hardware in a computer running a standard multitasking operating system. This design enables four to six independent laser traps with a visitation frequency of 10,000s(-1)trap(-1) and a timing jitter of +/-0.5 micros to be created. The design also achieves nanometer-resolution detection of displacement in all of the traps simultaneously via back focal-plane interferometry and only a single quadrant photodiode detector. Practical design considerations and limitations together with the use of fiberlasers in laser traps are discussed. Using this device, the mechanokinetics of multiple molecular motors or adhesion proteins may be measured simultaneously. We present the example biological application of two kinesin-coated beads in separate traps moving on different portions of a microtubule.


Composite wiring of metacarpal and phalangeal fractures.
Composite wiring techniques using various configurations of Kirschner pins and stainless steel wire sutures have been applied to the treatment of 63 fractures of the long bones of the hand. The secure fixation achieved allowed active motion within 1 week of operation. Thirty-three metacarpal fractures achieved a final mean total active motion of 256 degrees (standard deviation 13.4) (normal total active motion -260 degrees). Twenty-one phalangeal fractures achieved a mean total active motion of 215 degrees (standard deviation, 46 degrees). There were no instances of infection, malunion, nonunion, loss of reduction, or tendon rupture in the 63 fractures that were treated.


Pleuropneumonectomy for a large thymoma with multiple pleural dissemination using median sternotomy followed by posterolateral thoracotomy.
We present 2 cases of a large thymoma with invasion to the hilum of the lung and pleural dissemination. Case 1: a 47-year-old woman was diagnosed with a type B3 thymoma with abundant left pleural effusion and multiple pleural masses, Masaoka stage IVa. A radical resection was planned after chemical pleurodesis and systemic chemotherapy. The left main pulmonary artery and left upper and inferior veins were dissected and resected in the pericardium, while the left main bronchus was cut behind the pericardium through a median sternotomy. Next, the median incision was closed and a left posterolateral thoracotomy was made, thus allowing the pleuropneumonectomy to be safely performed. Case 2: a 47-year-old woman was diagnosed with a type B3 thymoma with lymph node swelling and multiple pleural masses, indicating Masaoka stage IVb. Following induction chemotherapy, a thymothymectomy combined with a right pleuropneumonectomy was performed under a median sternotomy followed by a right posterolateral thoracotomy. The left brachiocephalic vein (BCV) was reconstructed with a ringed polytetrafluoroethylene (PTFE) graft, followed by resection of the right BCV. Next, the right main pulmonary artery and right upper and inferior veins were resected in the pericardium, and the right main bronchus was cut behind the pericardium, followed by reconstruction of the right BCV. Finally, the median incision was closed and a right posterolateral thoracotomy was made, thus allowing performance of a safe pleuropneumonectomy. The median sternotomy allowed safe dissection of pulmonary vessels surrounding the hilum of the lung and, in combination with a posterolateral thoracotomy, was required for performing a pleuropneumonectomy in patients with a huge thymoma with pleural dissemination.


Activation of nuclear factor kappa B in Crohn's disease.
The location and degree of activation of nuclear factor kappa (NFkappaB), a primary transcription factor that plays a regulating role in immune and inflammatory responses, was determined in Crohn's disease using full thickness specimens of bowel collected at surgery. Resected specimens of inflamed and non-inflamed bowel were collected from thirteen patients with Crohn's disease and non-inflamed bowel from eleven control subjects. Prepared frozen sections were immunostained using a monoclonal antibody to the activated form of the p65 subunit of NFkappaB and the number of positive staining cells counted using a Lennox graticule. The number of cells positive for activated NFkappaB was significantly increased (p = 0.001 ) in all layers of inflamed Crohn's disease bowel, compared to non-inflamed bowel from controls. There was also a significant increase ( p = 0.009) in the number of positive cells, when compared to non-inflamed bowel from control subjects, in the submucosa of non-inflamed areas of Crohn's disease bowel. Cells positive for activated NFkappaB were provisionally identified by morphological criteria as mostly macrophages with some lymphocytes. There was no activation in endothelia. NFkappaB is activated within large mononuclear cells in all layers of inflamed areas of the bowel in Crohn's disease and may represent key events in the inflammatory process. Increased activation in the submucosa of non-inflamed Crohn's disease bowel provides further evidence of early immunological activation in macroscopically and microscopically uninvolved areas and an underlying abnormal immune system in Crohn's disease.


NHEJ pathway is involved in post-integrational DNA repair due to Ku70 binding to HIV-1 integrase.
HIV-1 integration results in genomic DNA gaps that are repaired by cellular DNA repair pathways. This step of the lentiviral life cycle remains poorly understood despite its crucial importance for successful replication. We and others reported that Ku70 protein of the non-homologous end joining pathway (NHEJ) directly binds HIV-1 integrase (IN). Here, we studied the importance of this interaction for post-integrational gap repair and the recruitment of NHEJ factors in this process. We engineered HIV-based pseudovirus with mutant IN defective in Ku70 binding and generated heterozygous Ku70, Ku80 and DNA-PKcs human knockout (KO) cells using CRISPR/Cas9. KO of either of these proteins or inhibition of DNA-PKcs catalytic activity substantially decreased the infectivity of HIV-1 with native IN but not with the mutant one. We used a recently developed qPCR assay for the measurement of gap repair efficiency to show that HIV-1 with mutant IN was defective in DNA post-integrational repair, whereas the wild type virus displayed such a defect only when NHEJ system was disrupted in any way. This effect was present in CRISPR/Cas9 modified 293T cells, in Jurkat and CEM lymphoid lines and in primary human PBMCs. Our data provide evidence that IN recruits DNA-PK to the site of HIV-1 post-integrational repair due to Ku70 binding-a novel finding that explains the involvement of DNA-PK despite the absence of free double stranded DNA breaks. In addition, our data clearly indicate the importance of interactions between HIV-1 IN and Ku70 in HIV-1 replication at the post-integrational repair step.


Pseudotumor of kidney.
Pyelocancerous backflow during retrograde pyelography is a roentgen sign indicating renal tumors. An example of a pseudotumor (renal hematoma caused by anticoagulation) is presented which displayed this type of backlfow, demonstrating the nonspecificity of the sign. The diagnostic, especially radiographic, findings of intrarenal hematoma are discussed.


Disorders of face perception and recognition.
Face recognition is one of the most complex visual tasks performed by the human brain. Data from monkeys suggest that area IT may play a key role in identifying faces, and functional imaging research suggests that the human homologue of IT may be located in the medial occipitotemporal cortex, where a FFA has been located. Damage to medial occipitotemporal structures on the right or bilaterally leads to prosopagnosia, the failure to recognize facial identity. Prosopagnosia is not a single functional disorder but a family of dysfunctions, with different patients having different degrees of impairments to various perceptual and memory stages involved in face processing. Understanding the perceptual basis of this disorder and epiphenomena, such as covert recognition, is a goal of current research. Deficits in face perception also may contribute to Capgras syndrome and may be related to the impaired social development of patients with Asperger syndrome. More recently, identified deficits in face processing include the false recognition of unfamiliar faces and the impaired extraction of social information from faces, independent of the recognition of identity. Many of these prosopagnosia and other face processing deficits can be placed in the context of cognitive models of face processing stages, which are being refined continually by data from neurologic patients and functional imaging in normal subjects.


The impact of age on the physical and cellular properties of the human limbal stem cell niche.
The limbal niche in the corneoscleral junction of the eye, habitat of the limbal epithelial stem cells (LESC), facilitates corneal epithelial regeneration by providing physical support and chemical signalling. Anatomical structures within the limbus, namely, limbal epithelial crypts and focal stromal projections, are believed to function as a putative niche for LESCs. In this study, the impact of age on the topography of this niche was investigated. Also, the relationship between niche topography and limbal epithelial cell phenotype was assessed. Ex vivo imaging of the limbus in cadaveric tissue of donors aged from infancy to 90 years was carried out using electron and confocal microscopy. The data suggested that the area occupied by the crypts was sharply reduced after the age of 60 years. The niche microstructures also became smoother with donor age. The phenotypic assessment of cultured limbal epithelial cells harvested from donors of different ages showed that the levels of putative stem cell markers as well as telomerase activity and telomere length remained unchanged, regardless of niche topography. However, the colony forming efficiency of the cultures was significantly reduced with age (p < 0.05). This is the first comprehensive study of the effect of age on the structural and phenotypic characteristics of the human limbal niche. The results have a significant biological value as they suggest a correlation of limbal architecture with decline of re-epithelialisation rate in older patients. Overall, the data also suggest that LESCs harvested from younger donors may be more suitable for cultured LESC therapy production.


Can mean platelet volume and mean platelet volume/platelet count ratio be used as a diagnostic marker for sepsis and systemic inflammatory response syndrome?
To determine whether the mean platelet volume (MPV) and MPV/platelet (PLT) values can be used in the study of sepsis and systemic inflammatory response syndrome (SIRS). In this retrospective case-controlled study, 69 sepsis, 69 SIRS patients, and 72 control group who were treated in the years 2012-2013 were reviewed, and both the MPV and MPV/PLT rates were evaluated in all groups. Statistically significant difference was found between sepsis, SIRS, and control groups when comparing the MPV and MPV/PLT ratio (p less than 0.05), and no significant difference was found between sepsis and SIRS groups in terms of MPV and MPV/PLT ratio (p more than 0.05). Mean platelet volume values for sepsis and control groups was 10.07/8.731 femtoliter (fL) (p=0.000), and 9.45/8.731 fL (p=0.000) for SIRS and control groups. In the group of sepsis patients, the MPV was found to be at cut-off 8.915, sensitivity 71%, and specificity 63.9%. In the group of patients with SIRS, MPV was found to be at cut-off 8.85, sensitivity 69.6%, and specificity 62.5%. For the MPV/PLT values, the specificity and sensitivity were found to be insignificant. This study shows that although there was no significant reduction in the PLT values between the sepsis and SIRS patients, the MPV and MPV/PLT ratio values were found to have significant differences. However, the specificity and sensitivity of the values were not reliable standard to be used as a test.


Autobiographical memory predicts postsurgical pain up to 12 months after major surgery.
Recent cross-sectional studies have identified differences in autobiographical memory (AM) among individuals with chronic pain, but the temporal relationship between the 2 is unknown. Moreover, AM has yet to be studied in patients undergoing major surgery. This study addressed these gaps by conducting a prospective, longitudinal study of memory performance, postsurgical pain, and psychosocial factors in 97 adult participants scheduled for major surgery. Memories were evaluated using the Autobiographical Memory Test before and one month after surgery when participants were asked to recall personal events related to positive and pain-related word cues. Responses were coded for level of specificity, emotional valence, and surgery-related content. Questionnaires assessing presence/absence of pain and psychological functioning were administered before and at 1-, 3-, 6-, and 12-month follow-ups. Generalized estimating equations modelled pain at each postsurgical time point with memory variables as predictors. As hypothesized, higher numbers of specific pain memories recalled before surgery predicted lower odds of pain across all time points (OR = 0.58, 95% CI [0.37-0.91]). Participants who took longer to recall pain memories before surgery (OR = 2.65, 95% CI [1.31-5.37]) and those who produced more surgery-related content at the one-month assessment (OR = 1.31, 95% CI [1.02-1.68]) had greater odds of reporting postsurgical pain up to 12 months later. These findings indicate that presurgical AM biases are risk factors for development and maintenance of postsurgical pain. To the extent that these biases are causal, presurgical interventions that modify the quality and content of patients' memories may prove to be promising strategies in the prevention of chronic postsurgical pain.


Dynamic analysis of the semiconductor laser as a current-controlled oscillator in the optical phased-lock loop: applications.
A methodology for treating the semiconductor laser as a current-controlled oscillator in an optical phase-lock loop is presented. The formalism is applied to phase demodulation of optical beams, reduction of phase noise by self-homodyning, and phase locking of a semiconductor laser array.


Psychosocial risks: is risk management strategic enough in business and policy making?
In times of continuous change and volatile markets, organizations are increasingly characterized by downsizing, work intensification, and resource rationalization. This has resulted in diversification, and the emergence of new risks within the field of occupational health and safety, with an important impact. This paper focuses on one such type of risk in the modern workplace-psychosocial risks. The current study aimed to explore stakeholder perspectives, regarding the extent to which psychosocial risks are incorporated into strategic risk management practices, at both the business and policy level. Semi-structured interviews were conducted with 14 professionals, representing employer, expert, policy maker, and trade union stakeholder perspectives. It was found that the majority of organizations do not sufficiently, if at all, understand and incorporate psychosocial risks into strategic decision making, whereby the key barrier related to practical difficulties of not knowing how to manage psychosocial risks adequately. The study found that there is a need to close the gap between policy and practice on a number of levels. Future recommendations comprise a policy framework and infrastructure underpinned by educational initiatives, partnerships, and networks to drive a shift in attitudes toward recognizing the duality of the concept of risk (including both potential negative and positive outcomes) and moving beyond simple regulatory compliance.


Epithelioid hemangioendothelioma of the right atrium invaded the superior vena cava: case report and review of literature.
Epithelioid hemangioendothelioma (EHE) is a rare hemangioma that can occur anywhere in the body. It occurs most commonly in the liver and lungs, rarely from the heart, and the etiology or risk factors are unclear. So far, timely detection and radical resection is a more acceptable treatment. Reviewing the literature, few cases of cardiac EHE have been reported. We present a rare case of EHE of the right atrium invaded the superior vena cava.


Effects of anti-Xa activity monitoring on the outcome of high-risk pregnancies treated with a prophylactic dose of low-molecular-weight heparin.
To evaluate if anti-Xa level monitoring and dose adjustment in women using a prophylactic dose of enoxaparin can decrease placenta-mediated pregnancy complications. This retrospective observational cohort study included pregnant women receiving enoxaparin prophylaxis, who were followed at the Thrombosis and Hemostasis Outpatient clinic between 2010 and 2017. The dose was adjusted according to enoxaparin anti-Xa levels in the study group or the weight of individuals in the control group. Of 585 women surveyed, 110 met the inclusion criteria; 63 of them were included in the study group and 47 in the control group. Mean starting dose was 46 versus 43 mg (p = .25), mean final dose was 52 mg versus 45 mg (p = .03) and dose adjustment was required in 37% versus 11% (p = .002) in the study and control groups, respectively. Twenty-eight percent of anti-Xa measurements in the second trimester were beneath the prophylactic threshold, compared to 11% and 16% in the first and third trimesters, respectively (p = .02). Labors ended with live birth in 91% versus 94% of cases (p = .5), 85% versus 68% of pregnancies were term (p = .05), 11% versus 23% of newborns were low birth weight (p = .1) and placenta-mediated pregnancy complications were documented in 9% versus 19%, (p = .17) in the study group relative to controls, respectively. The most prominent decrease in anti-Xa levels was observed in the second trimester. Monitored women had significantly more term deliveries and demonstrated a trend toward higher birth weight and fewer placenta-mediated pregnancy complications. Larger studies are needed to confirm improved pregnancy outcome in monitored women.


Validation of the Dyspnoea-12 and Multidimensional Dyspnea profile among older Swedish men in the population.
The Dyspnoea-12 (D12) and Multidimensional dyspnea profile (MDP) are commonly used instruments for assessing multiple dimensions of breathlessness but have not been validated in older people in the population. The aim of this study was to validate the D12 and MDP in 73-years old men in terms of the instruments' underlying factor structures, internal consistency, and validity. A postal survey was sent out to a population sample of 73-years old men (n = 1,193) in southern Sweden. The two-factor structures were evaluated with confirmatory factor analysis, internal consistency with Cronbach's alpha, and validity using Pearson´s correlations with validated scales of breathlessness, anxiety, depression, fatigue, physical/mental quality of life, body mass index (BMI), and cardiorespiratory disease. A total 684 men were included. Respiratory and cardiovascular disease were reported by 17% and 38%, respectively. For D12 and MDP, the proposed two-factor structure was not fully confirmed in this population. Internal consistency was excellent for all D12 and MDP domain scores (Cronbach's alpha scores > 0.92), and the instruments' domains showed concurrent validity with other breathlessness scales, and discriminant validity with anxiety, depression, physical/mental quality of life, BMI, and cardiorespiratory disease. In a population sample of 73-years old men, the D12 and MDP had good psychometrical properties in terms of reliability and validity, which supports that the instruments are valid for use in population studies of older men.


Coiled-coil response to mechanical force: global stability and local cracking.
Coiled coils are important structural motifs formed by two or more amphipathic α-helices that twist into a supercoil. These motifs are found in a wide range of proteins, including motor proteins and structural proteins, that are known to transmit mechanical loads. We analyze atomically detailed simulations of coiled-coil cracking under load with Milestoning. Milestoning is an approach that captures the main features of the process in a network, quantifying kinetics and thermodynamics. A 112-residue segment of the β-myosin S2 domain was subjected to constant-magnitude (0-200 pN) and constant-direction tensile forces in molecular dynamics simulations. Twenty 20 ns straightforward simulations at several load levels revealed that initial single-residue cracking events (Ψ > 90°) at loads <100 pN were accompanied by rapid refolding without either intra- or interhelix unfolding propagation. Only initial unfolding events at the highest load (200 pN) regularly propagated along and between helices. Analysis of hydrophobic interactions and of interhelix hydrogen bonds did not show significant variation as a function of load. Unfolding events were overwhelmingly located in the vicinity of E929, a charged residue in a hydrophobic position of the heptad repeat. Milestoning network analysis of E929 cracking determined that the mean first-passage time ranges from 20 ns (200 pN) to 80 ns (50 pN), which is ∼20 times the mean first-passage time of an isolated helix with the same sequence.


Fusarium toxin residues in physiological samples of piglets.
Physiological samples of 100 piglets fed diets containing 0.01, 0.06, 0.15, 0.22 and 0.42 mg ZON and 0.2, 0.8, 1.0, 1.9 and 3.9 mg DON per kg over a period of 35±1.5 days were investigated for concentrations of deoxynivalenol (DON) and zearalenone (ZON) and their metabolites.DON was detected in serum, bile and urine in increasing concentrations corresponding to the diet contamination. The metabolite de-epoxy-DON was detected only in urine. The DON contamination of the diet was closely reflected by the serum concentrations of the piglets.ZON and its metabolite α-zearalenol were detected in bile fluid, liver and urine, while β-zearalenol was only detected in bile fluid. In serum neither ZON nor its metabolites were found. The total concentration of ZON plus its metabolites in the bile fluid corresponded well with the dietary contamination.For all analyses it has to be noted that toxin residues were detectable even in individual samples of piglets fed the control diet containing 0.01 mg ZON/kg and 0.2 mg DON/kg.


Risk of hip/femur fractures during the initiation period of α-adrenoceptor blocker therapy among elderly males: a self-controlled case series study.
This study aimed to evaluate the risk of hip/femur fractures during the initiation period of α-adrenoceptor blocker therapy using the National Health Insurance claims database, Taiwan, with a self-controlled case series design. All male beneficiaries aged over 50 years as of 2007, who were incident users of α-adrenoceptor blockers and also had a diagnosis of hip/femur fracture within the 2007-2009 study period were identified. The first day when the α-adrenoceptor blocker was prescribed was set as the index date. We partitioned the initial 21 day period following the index date as the post-exposure risk period 1, days 22-60 after the index date as the post-exposure risk period 2, the 21 day period prior to the index date as the pre-exposure risk period 1 and days 22-60 prior to the index date as the pre-exposure risk period 2. The remainder of the study period was defined as the unexposed period. The incidence rate ratio (IRR) of hip/femur fractures within each risk period compared with the unexposed period was estimated using a conditional Poisson regression model. A total of 5875 men were included. Compared with the unexposed period, the IRR of hip/femur fractures was 1.36 (95% confidence interval 1.06, 1.74, P = 0.017) within the post-exposure risk period 1 for patients without concomitant prescriptions of anti-hypertensive agents. Use of α-adrenoceptor blockers was associated with a small but significant increase in the risk of hip/femur fractures during the early initiation period in patients without concomitant prescriptions of anti-hypertensive agents.


Novel mutation located in EC7 domain of protocadherin-15 uncovered by targeted massively parallel sequencing in a family segregating non-syndromic deafness DFNB23.
Hereditary hearing loss is a clinically and genetically heterogeneous disorder associated with mutations of a large number of diverse genes. In this study we applied targeted capture and massively parallel sequencing to identify the disease-causing gene of a Chinese family segregating recessive inherited deafness. After excluding mutations in common deafness genes GJB2, SLC26A4, mitochondrial m.1555A>G, genomic DNA of the proband of family GDSW24 was subjected to targeted next-generation sequencing. Subsequently, a candidate homozygous mutation was confirmed by Sanger sequencing. A novel PCDH15 c.2367_2369delTGT/p.V788-homozygous mutation was detected. In this family, no obvious vestibular disorder was found. The in-frame mutation c.2367_2369delTGT is located in the evolutionarily conserved EC7 domain of Protocadherin-15 and was predicted to be pathogenic. The novel homozygous mutation in a family segregating non-syndromic hearing loss family supports previous reported observations that PCDH15 does not only causes Usher syndrome type 1F, but also DFNB23.


Cardiovascular safety of glucose-lowering agents as add-on medication to metformin treatment in type 2 diabetes: report from the Swedish National Diabetes Register.
To investigate the relative safety of various glucose-lowering agents as add-on medication to metformin in type 2 diabetes in an observational study linking five national health registers. Patients with type 2 diabetes who had been on metformin monotherapy and started another agent in addition to metformin were eligible for inclusion. The study period was 2005-2012. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality, cardiovascular disease (CVD), coronary heart disease (CHD), stroke and congestive heart failure (CHF) were estimated using Cox proportional hazards models, weighted for a propensity score. Of the 20 422 patients included in the study, 43% started on second-line treatment with sulphonylurea (SU), 21% basal insulin, 12% thiazolidinedione (TZD), 11% meglitinide, 10% dipeptidyl peptidase-4 (DPP-4) inhibitor, 1% glucagon-like peptide-1 (GLP-1) receptor agonist and 1% acarbose. At the index date, the mean patient age was ~60 years for all groups except the GLP-1 receptor agonist (56.0 years) and SU (62.9 years) groups. Diabetes duration and glycated haemoglobin levels were similar in all groups. When compared with SU, basal insulin was associated with an 18% higher risk and TZD with a 24% lower risk of mortality [HR 1.18 (95% CI 1.03-1.36) and 0.76 (95% CI 0.62-0.94)], respectively. DPP-4 inhibitor treatment was associated with significantly lower risks of CVD, fatal CVD, CHD, fatal CHD and CHF. This nationwide observational study showed that second-line treatment with TZD and DPP-4 inhibitor as add-on medication to metformin were associated with significantly lower risks of mortality and cardiovascular events compared with SU, whereas basal insulin was associated with a higher risk of mortality.


Interventions to prevent surface transmission of an infectious virus based on real human touch behavior: a case study of the norovirus.
Infectious viruses (e.g., SARS-CoV-2, norovirus) can transmit through surfaces. Norovirus has infected millions of individuals annually. Interventions on norovirus transmission in high-risk indoor environment are important. This study focused on a restaurant in Guangzhou, China. More than 41,000 touches by both diners and staff members were collected using video cameras. A surface transmission model was developed and combined with these real human touch behaviors to analyze the effectiveness of different norovirus prevention strategies. When the virus carrier was a diner, the virus intake fraction of diners in the same table was the highest. Increasing the touch frequency on personal private surfaces would reduce the virus exposure. The virus intake fraction was reduced by 18.4% on average if public surfaces were not touched. Optimization on surface materials could reduce the virus intake fraction by 86.6%. Additionally, disinfecting tablecloths, clothes of diners, and chairs were the three most effective surface disinfection strategies. Controlling human touch behavior (e.g., reducing the self-touches on mucous membranes) is more effective than surface disinfection in controlling norovirus transmission, but surface disinfection cannot be ignored because human behavior is difficult to be controlled.


Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group.
A series of gamma-amino alcohols were synthesized and screened for reuptake inhibition and noncompetitive NMDA antagonism. Compound (+/-)-3f simultaneously and potently inhibits reuptake of 5-HT, NE, and DA, representing a potential wide-spectrum reuptake inhibitor antidepressant. In addition, comparative rat and human studies uncovered a species-selective DA reuptake inhibitor (+/-)-2e, KD(hDAT)/KD(rDAT) = 97.


Consent for teaching: the experience of women attending a gynaecology clinic.
To examine women's experience of the consent process for involvement in medical education in a teaching hospital. Questionnaire survey. The study involved 181 (90% response rate) women aged 17-79 years who attended 1 gynaecology clinic. A gynaecology clinic in an inner London teaching hospital. Women were broadly positive about the presence of students in gynaecology clinics. The current process relies on implied consent and women actively opting out of involvement. Despite hospital policy to inform all outpatients in their appointment letter that students may be present at the clinic, 58% of patients did not recall being informed in this way. Although 91% of women did not object to student presence, only 65% reported having been asked if they wanted it. Subjective feeling of choice about the student presence was associated with advance notice, either by letter or previous experience of students at clinics. Women differentiated between consent for different aspects of interaction with students. Notification of the presence of students in standard appointment letters does not adequately inform patients. Clinical teachers need to ensure that the measures in place to inform women and to seek their active consent about involvement in teaching are robust.


Fetal age assessment based on femur length at 10-25 weeks of gestation, and reference ranges for femur length to head circumference ratios.
The aim of the present study is to establish new reference charts for gestational age assessment based on fetal femur length (FL), and new reference ranges for FL to head ratios at gestational weeks 10-25, and to determine the effect of maternal and fetal factors on these charts. Six hundred fifty low-risk women with regular menstrual periods and singleton pregnancies were recruited to a prospective cross-sectional study after obtaining written consent. FL, outer-outer biparietal diameter (BPD), and head circumference (HC) were measured at 10-25 weeks of gestation. We used regression analysis in order to construct mean curves and to assess the effect of maternal and fetal factors on age assessment. The new chart for age assessment by means of FL was based on 636 measurements. The 95% CI of the mean corresponded to <1 day. The variation between the mean and the 90th percentile was 5, 6, and 7 days at 13, 18, and 23 weeks, respectively, similar to the results when using BPD or HC. Maternal age modestly influenced gestational age assessment (1.3 days/10 years, P = 0.005), whereas smoking, height, body mass index, multiparity, fetal sex, cephalic index, and breech presentation had no impact. Reference charts for FL to head ratios have been presented. Maternal age, fetal sex, and cephalic index influenced the FL/BPD ratio, whereas only fetal sex influenced FL/HC. Fetal age assessment based on FL is an equally robust method as using HC. FL/HC is a more robust ratio to characterize fetal proportions than is FL/BPD.


Solvent-assisted synthesis of Ag2Se and Ag2S nanoparticles on carbon fabric for enhanced thermoelectric performance.
The challenge of developing low-cost, highly flexible, and high-performance thermoelectric (TE) materials persists due to the low thermoelectric efficiency of conducting polymers and the inflexibility of inorganic materials. In this study, we successfully integrated Ag2Se and Ag2S with highly conductive carbon fabric (CF) to produce a flexible thermoelectric material. A facile one-step solvothermal method was employed to synthesize the Ag2Se-CF and Ag2S-CF, which were then subjected to X-ray analysis to confine the phase formation of Ag2Se and Ag2S on the carbon fabric. The analysis revealed that Ag2Se and Ag2S nanoparticles were tightly packed on the surface of carbon fabric, and compositional analysis confirmed the interaction between the material and carbon fabric. The thermoelectric properties of Ag2Se-CF and Ag2S-CF were significantly altered due to carrier concentration and mobility variations, resulting in a low power factor of 6.7 μW/mK2 for Ag2Se-CF and a high-power factor of 24 μW/mK2 at 373 K for Ag2S-CF. The growth of Ag2Se-CF and Ag2S-CF on carbon fabric led to an enhancement in their thermoelectric properties. Further, TE legs were fabricated using the Ag2Se-CF (p-type) and Ag2S-CF (n-type), and the fabricated legs exhibited an output voltage of ∼20 mV to ∼86.65 mV at a temperature gradient (ΔT) of 3-8 K. This work represents a cutting-edge approach to the fabrication of high-performance, wearable thermoelectric devices.


Risk of Adverse Drug Events Observed with Baricitinib 2 mg Versus Baricitinib 4 mg Once Daily for the Treatment of Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
On 23 April 2018, the Food and Drug Administration-based Advisory Committee approved the use of baricitinib 2 mg for the treatment of rheumatoid arthritis and suggested the possibility of serious adverse events associated with baricitinib 4 mg. Hence, we aimed to systematically compare the risk of adverse drug events observed with baricitinib 2 mg versus 4 mg for the treatment of patients with rheumatoid arthritis. Electronic databases including the Cochrane library, MEDLINE, EMBASE and http://www.ClinicalTrials.gov were searched for relevant English publications until April 2018. Adverse drug events at 12 weeks and 24 weeks were considered as the clinical endpoints. RevMan 5.3 software was used to analyze the data whereby risk ratios (RR) and 95% confidence intervals (CI) were calculated. Four trials consisting of a total of 959 participants were included in this analysis. At 12 weeks, no significant difference was observed between 2 mg and 4 mg baricitinib for serious adverse events (RR 1.33; 95% CI 0.63-2.78; p = 0.46), any adverse events after the start of therapy (RR 1.09; 95% CI 0.98-1.21; p = 0.13), discontinuation of drugs due to adverse events (RR 1.19; 95% CI 0.61-2.34; p = 0.60), malignancies (RR 3.03; 95% CI 0.12-73.90; p = 0.50), and major adverse cardiac events (RR 2.95; 95% CI 0.12-71.91; p = 0.51). Infections including herpes zoster infections and serious infections were also similarly manifested. At 24 weeks, serious adverse events (RR 1.84; 95% CI 1.02-3.30; p = 0.04) were significantly higher with baricitinib 4 mg compared with the 2-mg dosage. However, total adverse events after the start of therapy, discontinuation of drug due to adverse events, malignancies, major adverse cardiac events, infections including herpes zoster, and serious infections were not significantly different between the two doses. No significant differences in adverse drug events were observed between baricitinib 2 mg and 4 mg at 12 weeks' follow-up. However, this analysis showed the risk of serious adverse events to be significantly higher with baricitinib 4 mg compared with baricitinib 2 mg at 24 weeks' follow-up. This hypothesis should be confirmed in larger trials with longer follow-up time periods.


Chronic Use of a Sensitized Bionic Hand Does Not Remap the Sense of Touch.
Electrical stimulation of tactile nerve fibers that innervated an amputated hand results in vivid sensations experienced at a specific location on the phantom hand, a phenomenon that can be leveraged to convey tactile feedback through bionic hands. Ideally, electrically evoked sensations would be experienced on the appropriate part of the hand: touch with the bionic index fingertip, for example, would elicit a sensation experienced on the index fingertip. However, the perceived locations of sensations are determined by the idiosyncratic position of the stimulating electrode in the nerve and thus are difficult to predict or control. This problem could be circumvented if perceived sensations shifted over time to become consistent with the position of the sensor that triggers them. We show that, after long-term use of a neuromusculoskeletal prosthesis that featured a mismatch between the sensor location and the resulting tactile experience, the perceived location of the touch did not change.


Cell-to-cell movement of mitochondria in plants.
We report cell-to-cell movement of mitochondria through a graft junction. Mitochondrial movement was discovered in an experiment designed to select for chloroplast transfer from Nicotiana sylvestris into Nicotiana tabacum cells. The alloplasmic N. tabacum line we used carries Nicotiana undulata cytoplasmic genomes, and its flowers are male sterile due to the foreign mitochondrial genome. Thus, rare mitochondrial DNA transfer from N. sylvestris to N. tabacum could be recognized by restoration of fertile flower anatomy. Analyses of the mitochondrial genomes revealed extensive recombination, tentatively linking male sterility to orf293, a mitochondrial gene causing homeotic conversion of anthers into petals. Demonstrating cell-to-cell movement of mitochondria reconstructs the evolutionary process of horizontal mitochondrial DNA transfer and enables modification of the mitochondrial genome by DNA transmitted from a sexually incompatible species. Conversion of anthers into petals is a visual marker that can be useful for mitochondrial transformation.


Experience with endoscopic axillary lymphadenectomy using needlescopic instruments in patients with breast cancer: a preliminary report.
The purpose of this study was to evaluate the safety and efficacy of endoscopic axillary lymphadenectomy using needlescopic instruments in patients with breast cancer. Five patients with breast cancer were treated by partial mastectomy and endoscopic axillary lymphadenectomy. We evaluated the results of the surgical procedure and the postoperative course. In all the patients, endoscopic axillary lymphadenectomy was performed successfully. The mean duration of the operation was 105.4 min, the mean blood loss 19.4 ml, and the mean number of dissected axillary lymph nodes 13. There were no intra- or postoperative complications. The mean amount of lymphorrhea was 131.2 ml, and the mean duration of drainage was 3.6 days. No postoperative analgesics were administered. Endoscopic axillary lymphadenectomy can be performed safely with needlescopic instruments, but further study is needed to establish this technique.


Bacterial contamination of pulmonary artery catheters.
The catheter tips of 152 patients, who were haemodynamically supervised by pulmonary artery monitoring or continuous cardiac output determination, were bacteriologically examined. 106 cultures remained sterile, 21 cultures revealed a growth of non pathogenic organisms. Staphylococcus aureus was cultured 15 times, pseudomonas aeruginosa 4 times, Citrobacter as well as Escherichia coli twice, and Klebsiella and Enterobacter once each. There was no statistically significant connection between dwelling period and contamination. Also diabetes mellitus or corticoid medication in high dosage had no significant influence on contamination rate.


[Retreatment after excimer laser photorefractive keratectomy].
To evaluate the efficacy and safety of reoperation of residual myopia because of regression, undercorrection with or without coexisting severe corneal haze after excimer laser photorefractive keratectomy (PRK). A VISK 20/20 excimer laser was used to treat myopia of -1.00 to -16.50 diopters (spherical equivalent) at corneal plane. 35 patients (51 eyes) who had residual myopia because of regression, undercorrection with or without coexisting severe corneal haze after initial PRK were retreated by using PRK and phototherapeutic keratectomy. At 12 months after retreatment, the rates of uncorrected visual acuity more than or equal to 10/20 or 20/20 were 82.6% and 39.1% respectively, 100.0% and 50.0% in myopia up to -6.00 D, 73.3% and 33.3% in myopia of -6.25 to -16.50 D respectively. 86.3% of eyes were within +/- 1.00 diopters of desired emmetropia. Corneal haze after retreatment was not greater than that observed after initial procedures. The residual myopia because of regression, undercorrection with or without severe corneal haze after initial PRK can be successfully retreated. Although the therapeutic result of retreatment of PRK is less successful than that of the initial procedure, retreatment appears to enhance it.


The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease.
Streptococcus pneumoniae is a Gram-positive bacterial pathogen that colonizes the mucosal surfaces of the host nasopharynx and upper airway. Through a combination of virulence-factor activity and an ability to evade the early components of the host immune response, this organism can spread from the upper respiratory tract to the sterile regions of the lower respiratory tract, which leads to pneumonia. In this Review, we describe how S. pneumoniae uses its armamentarium of virulence factors to colonize the upper and lower respiratory tracts of the host and cause disease.


Ferritin as an early marker of graft rejection after allogeneic hematopoietic stem cell transplantation in pediatric patients.
Diagnosis of adverse events following hematopoietic stem cell transplantation (HSCT) is mainly assigned to clinical symptoms or biopsies and thus rather unspecific and/or invasive. Studies indicate a distinct role of serum ferritin in HSCT and its correlation with adverse events such as graft-versus-host disease (GvHD), veno-occlusive disease (VOD), or infections. However, published data on the relevance of ferritin as a prognostic marker for post-transplant adverse events is rare, especially in pediatric patients. The present study analyzes ferritin plasma concentrations of 138 pediatric patients after HSCT between 2007 and 2010 including the control group (n = 21). Given the initial results regarding ferritin as a significant predictor for acute graft rejection after allogeneic HSCT in 9 of the 138 pediatric patients, serum ferritin of all pediatric patients (n = 27) who experienced graft rejection between 2007 and 2014 was analyzed. In addition, laboratory parameters including C-reactive protein (CRP), lactate dehydrogenase (LDH), fibrinogen, and D-dimer as possible differentiation markers for graft rejection were determined. In 24 (88.9 %) of the 27 pediatric patients with graft rejection, a significant increase of ferritin levels was observed 1 to 7 days prior to (P < 0.0001) and at the time of graft rejection (P < 0.0001). Moreover, there was an increase of D-dimer, CRP, LDH, and fibrinogen 1-7 days before graft rejection. Ferritin increased significantly at time of VOD (P = 0.0067), at time of intestinal (P < 0.0001) and skin GvHD (P < 0.0001), and at time of sepsis (P = 0.0005) and bacteremia (P = 0.0029). Ferritin might serve as a readily available identification marker for differentiation and identification of adverse events after HSCT in combination with other laboratory markers.


Pigs' management practices and exposure to Trichinella spp. in pigs and warthogs in the northern area of Senegal.
Trichinellosis is a neglected and emerging foodborne zoonosis in Africa. Trichinella infection occurs through the consumption of raw or undercooked infected meat and meat products. This study aimed to assess pigs' management practices and determine the exposure of pigs and warthogs to Trichinella spp. in the northern area of Senegal. Surveys and observations were carried out among 40 pig farmers to assess husbandry practices regarding Trichinella spp. life cycle. In addition, 201 pig meat juices and 83 warthog meat juices were extracted and tested for anti-Trichinella antibodies by indirect enzyme-linked immunosorbent assay. Most (97%) of farms practiced a traditional farming system with free-ranging of pigs in 85% of farms. Farms had local pig breed without housing and supplementary feeding. Some farmers (27.5%) used slaughter waste to feed pigs and farmers were not aware that free-range farming is a source of infection to Trichinella infection. They were also unaware that some pig diseases could be transmitted to humans. The seroprevalence of Trichinella infection was 10.9% (95% confidence interval [CI]: 6.6-15.2%) in pigs and 10.8% (95% CI: 4.16-17.52%) in warthogs with significantly higher seroprevalence in male (22.2%: 95% CI: 6.6-37.8%) compared to female (9.2%; 95% CI: 4.9-13.5%) (p < 0.05). The confirmation of exposure to Trichinella spp. in this area in pigs and warthogs shows a significant risk of transmission of this disease to humans if the farming conditions and the health surveillance system are not respected. However, control measures are needed to reduce any risk of transmission of Trichinella infection to humans.


Phase I study of oral S-1 plus Cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer.
To determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable Stage III non-small-cell lung cancer (NSCLC). S-1 was administered orally twice daily for 14 days and cisplatin on Days 1 and 8 of each cycle; this was repeated every 3 weeks. Doses of each drug were planned as follows: level 0, 50/40; level 1, 60/40; level 2, 70/40; level 3, 80/40 (S-1 [mg/m(-2)/day(-1)]/cisplatin [mg/m(-2)/day(-1)]). Thoracic radiation therapy was administered in 2 Gy fractions five times weekly to a total dose of 60 Gy. Ten patients were enrolled in this study. All patients received 60 Gy of thoracic radiotherapy and 7 (70%) patients received four cycles of chemotherapy. At level 1, 2 of 3 patients experienced a delay exceeding 10 days in the cisplatin administration of Day 29. Grade 4 neutropenia and Grade 3 fever occurred in 1 and 1 patients, respectively. Nonhematologic toxicities were mild. None developed >or=Grade 3 esophagitis or lung toxicity. At level 0, 2 of 7 patients developed dose-limiting toxicity. Thus, level 1 was considered the MTD and Level 0 was selected as the RD. Objective responses were seen in all patients. The RD is the level 0 dose, and this regimen is a feasible and well-tolerated regimen for the treatment of patients with Stage III NSCLC.


A simultaneous outbreak of Serratia marcescens and Klebsiella pneumoniae in a neonatal intensive care unit.
We describe two concurrent outbreaks of Serratia marcescens and Klebsiella pneumoniae in a neonatal intensive care unit (NICU). Over a 16-month period, a total of 27 infants were either colonized (N=14) or infected (N=13). There were 15 cases of S. marcescens and 11 cases of K. pneumoniae. Both micro-organisms were involved in one fatal case. Seven preterm babies developed septicaemia, two had bacteraemia, three had respiratory infections and one had purulent conjunctivitis. The S. marcescens and K. pneumoniae isolates were investigated by three molecular methods: enterobacterial repetitive intergenic consensus polymerase chain reaction (PCR), arbitrary primed PCR with M13 primer, and random amplification of polymorphic DNA. Different patterns were found in the 16 S. marcescens epidemic isolates from 16 newborn infants. The major epidemic-involved genotype was linked to the first nine cases and this was subsequently replaced by different patterns. Eight different typing profiles were also determined for the 13 K. pneumoniae isolates from 12 newborn infants. Four K. pneumoniae bacteraemic strains proved to be identical. In conclusion, the typing results revealed that two different micro-organisms (S. marcescens and K. pneumoniae) were simultaneously involved in invasive nosocomial infections in preterm newborns. Two simultaneous clusters of cases were documented. Heterogeneous genotypes among both species were also demonstrated to be present in the NICU at the same time. A focal source for both micro-organisms was not identified but cross-transmission through handling was probably an important route in this outbreak. Strict adherence to handwashing policies, cohorting, isolation of colonized and infected patients, and rigorous environmental hygiene were crucial measures in the containment of the epidemic.


Human airway trypsin-like protease induces mucin5AC hypersecretion via a protease-activated receptor 2-mediated pathway in human airway epithelial cells.
Mucus hypersecretion is a common feature in chronic airway diseases, and serine proteases play a critical role in this process. However, the mechanisms by which serine proteases induce mucin5AC hypersecretion have not been fully explored. In this study, we characterized human airway trypsin-like protease (HAT), a serine protease that is found in the mucoid sputum of patients with chronic airway diseases and is an agonist of protease-activated receptor 2 (PAR2)-induced cellular responses in human bronchial epithelial cells (16HBE). We also investigated the potential involvement of PAR2 in this process. We found that both HAT and PAR2-AP enhance the exocytosis of mucin5AC protein, whereas HAT, but not PAR2-AP, enhances the expression of mucin5AC mRNA. PAR2 is expressed at a much higher level in the cells than the other three PARs. Transfection with an siRNA against the PAR2 receptor or Gαq/11 protein or pretreatment with the Gαq/11 protein inhibitor YM-254890, the PLC inhibitor U73122 or the intracellular Ca(2+) chelator BAPTA-AM all effectively attenuated the HAT-induced cellular responses. Taken together, these results indicate that HAT can stimulate mucin5AC hypersecretion through a PAR2-mediated signaling pathway in 16HBE cells. Thus, PAR2 could represent a novel therapeutic target for chronic airway diseases with mucus hypersecretion.


Effect of varicocelectomy on serum inhibin B levels in infertile patients with varicocele.
In recent years serum inhibin B level has been proposed as a major indicator for Sertoli cell function and spermatogenesis. This study evaluated the effect of varicocelectomy on serum inhibin B levels and semen parameters in infertile patients with varicocele. Thirty consecutive patients with varicocele who were complaining of infertility with oligoasthenospermia on sperm analysis were included in the study. All the patients underwent subinguinal varicocelectomy. Spermogram, serum inhibin B levels and hormone analysis were performed at 6-month postoperative follow-up. The mean age of the patients was 24.06+/-3.6 years. There was no statistically significant difference between the mean serum follicle-stimulating hormone, luteinizing hormone, prolactin and testosterone levels of the patients before and after the treatment (p > 0.05). There was a statistically significant improvement in sperm concentration, forward progressive motility and serum inhibin B levels after the treatment (p < 0.05). Serum inhibin B level as an endocrine marker combined with a spermogram could provide efficient data for evaluating the effect of varicocelectomy on spermatogenesis.


Sex ratio response of the parasitoid wasp Muscidifurax raptor to other females.
This study examines the sex ratio response of the parasitoid wasp Muscidifurax raptor to conspecific and confamilial females in relation to two groups of functional sex ratio models, local mate competition and host quality models. In some but not all experiments, M. raptor females produced a greater proportion of sons in the presence of a conspecific female than when alone, and this sex ratio effect carried over for a day after the females were isolated from each other M. raptor females also produced a greater proportion of sons in the presence of a female of the confamilial parasitoid Spalangia cameroni than when alone (although only on the second day of exposure to S. cameroni, not on the first). M. raptor's sex ratio increase in the presence of conspecifics is consistent with local mate competition models but not with host quality models because the presence of a conspecific female did not cause there to be more, and thus potentially smaller, offspring developing per host. In contrast, the presence of a S. cameroni female did cause there to be more offspring developing per host than when a M. raptor female was alone; thus M. raptor's sex ratio increase in the presence of S. cameroni may be explained by host quality models. An alternative explanation for the sex ratio increase in response to confamilials is that only a sex ratio response to conspecifics may be adaptive, due to local mate competition; but M. raptor females may be unable to distinguish between conspecific and S. cameroni females.


Retracted: Effects of Bevacizumab Combined with Chemotherapy on CT, CyFRA21-1, and ProGRP and Prognosis of Lung Cancer Patients under Nursing Intervention.
[This retracts the article DOI: 10.1155/2022/9422902.].


Effects of sage extract on memory performance in mice and acetylcholinesterase activity.
Salvia officinalis L. (sage) has been widely used in the Tunisian traditional medicine for the treatment of digestive system and memory disorders. This work aims to investigate the anti-amnesiac and antioxidant activity of aqueous extract of S. officinalis (ASOE) in mice. Evaluation of memory functions in rodents was assessed by Y-maze active test after an initial acquisition phase. Results showed that the S. officinalis aqueous extract had high total phenolic contents (6.2mg gallic E/g extract) and flavonoids (2.44mg catechin E/g extract). It exhibited an interesting scavenging activity (IC50=14.5μg/ml). The mice treated with 300mg/kg body weight for 7 days exhibited a significant decrease in avoidance and discrimination errors during a retention trial compared to control group (P<0.05). Acetylcholinesterase (AChE) activity significantly decreased in mice treated with the extract of sage. These findings suggested that aqueous extract of sage leaves possess a mnemonic effect on adult male mice, confirming their use in traditional medicine.


Production of ethanol 3G from Kappaphycus alvarezii: evaluation of different process strategies.
This study evaluated the potential of Kappaphycus alvarezii as feedstock for ethanol production, i.e. ethanol 3G. First, aquatic biomass was subjected to a diluted acid pretreatment. This acid pretreatment generated two streams--a galactose-containing liquid fraction and a cellulose-containing solid fraction, which were investigated to determine their fermentability with the following strategies: a single-stream process (simultaneous saccharification and co-fermentation (SSCF) of both fractions altogether), which achieved 64.3 g L(-1) of ethanol, and a two-stream process (fractions were fermented separately), which resulted in 38 g L(-1) of ethanol from the liquid fraction and 53.0 g L(-1) from the simultaneous saccharification and fermentation (SSF) of the solid fraction. Based on the average fermentable carbohydrate concentration, it was possible to obtain 105 L of ethanol per ton of dry seaweed. These preliminaries results indicate that the use of the macro-algae K. alvarezii has a good potential feedstock for bioethanol production.


Sequential induction of embryonic and adult forms of glutamic acid decarboxylase during in vitro-induced neurogenesis in cloned neuroectodermal cell-line, NE-7C2.
The expression of different forms of glutamate decarboxylases and GABA was investigated in the course of retinoic acid-induced neuronal differentiation of NE-7C2 cell-line established from brain vesicles of 9-day-old mouse embryos lacking functional p53 gene. Non-induced NE-7C2 cells expressed embryonic GAD mRNAs with a low level of embryonic GAD25 protein and did not contain detectable amounts of GABA. Addition of 10(-6) M retinoic acid induced the expression of N-tubulin and a significant increase in the level of embryonic GAD messages and GAD25 protein in early stage differentiating neurones. The enzymatically active embryonic GAD44 was detected at later stages of induction in neurone-like cells and showed a maximum of expression at the time of neurite elongation and network formation. With the advance of neuronal maturation, the expression of embryonic forms declined while the adult GAD65 and GAD67 transcripts became dominant. GABA-containing neurones were first demonstrated on the sixth day of induction coinciding with the peak of GAD44 expression and the beginning of GAD65 expression. The sequential induction of different GAD forms and the stage-dependent GABA synthesis in NE-7C2 cells is highly reminiscent of the temporal pattern found in vivo and suggests that these processes might be involved in the differentiation of neuronal progenitors.


New insights into hidradenitis suppurativa diagnosis via salivary infrared biosignatures: A pilot study.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease which can lead to a prolonged physical disability. HS diagnosis is exclusively clinical with the absence of biomarkers. Our study aims at assessing the HS-diagnostic potential of infrared spectroscopy from saliva, as a biofluid reflecting the body's pathophysiological state. Infrared spectra from 127 patients (57 HS and 70 non-HS) were processed by multivariate methods: principal component analysis coupled with Kruskal-Wallis or Mann-Whitney tests to identify discriminant spectral wavenumbers and linear discriminant analysis to evaluate the performances of HS-diagnostic approach. Infrared features, mainly in the 1300 cm-1 -1600 cm-1 region, were identified as discriminant for HS and prediction models revealed diagnostic performances of about 80%. Tobacco and obesity, two main HS risk factors, do not seem to alter the infrared diagnosis. This pilot study shows the potential of salivary "liquid biopsy" associated to vibrational spectroscopy to develop a personalized medical approach for HS patients' management.


Trio exome sequencing is highly relevant in prenatal diagnostics.
About 3% of newborns show malformations, with about 20% of the affected having genetic causes. Clarification of genetic diseases in postnatal diagnostics was significantly improved with high-throughput sequencing, in particular through whole exome sequencing covering all protein-coding regions. Here, we aim to extend the use of this technology to prenatal diagnostics. Between 07/2018 and 10/2020, 500 pregnancies with fetal ultrasound abnormalities were analyzed after genetic counseling as part of prenatal diagnostics using WES of the fetus and parents. Molecular genetic findings could explain ultrasound abnormalities in 38% of affected fetuses. In 47% of these, disease-causing de novo variants were found. Pathogenic variants in genes with autosomal recessive or X-linked inheritance were detected in more than one-third (70/189 = 37%). The latter are associated with increased probability of recurrence, making their detection important for further pregnancies. Average time from sample receipt to report was 12 days in the recent cases. Trio exome sequencing is a useful addition to prenatal diagnostics due to its high diagnostic yield and short processing time (comparable to chromosome analysis). It covers a wide spectrum of genetic changes. Comprehensive interdisciplinary counseling before and after diagnostics is indispensable.


Accuracy of swirl sign for predicting hematoma enlargement in intracerebral hemorrhage: a meta-analysis.
Hematoma enlargement happens in about 30% patients with intracerebral hemorrhage, which is reported to be closely correlated with poor prognosis. Swirl sign has been reported to have correlation with hematoma enlargement. This meta-analysis analyzed the accuracy of swirl sign for predicting hematoma enlargement in intracerebral hemorrhage. Five databases were searched for potentially eligible literature. Studies were included if they were about the predictive properties of swirl sign for hematoma enlargement in intracerebral hemorrhage. Sensitivity and specificity of swirl sign for hematoma enlargement prediction were pooled. Pooled positive and negative likelihood ratios were also calculated. Six studies with 2647 patients were finally included in meta-analysis. The pooled sensitivity and specificity of swirl sign were 0.45 (95%CI 0.32-0.59) and 0.79 (95%CI 0.73-0.84), respectively. The pooled positive likelihood ratio of swirl sign was 2.2 (95%CI 1.8-2.5). In contrast, the pooled negative likelihood ratio of swirl sign was 0.69 (95%CI 0.57-0.84). This meta-analysis suggests that swirl sign has the relatively high specificity for hematoma enlargement prediction in patients with intracerebral hemorrhage.