Creating ophthalmology experiences in undergraduate medical education: pilot of a cased-based learning ophthalmology tool.
To evaluate medical student perceptions of a novel ophthalmology resource delivered through facilitated workshops in the core clerkship curriculum. We created www.2020sim.com, a free case-based learning (CBL) ophthalmology tool, adapted from NephSIM (www.nephsim.com). The tool was first piloted with the internal medicine (IM) residents. After confirming a need, we focused on undergraduate medical education (UME) by expanding the 20/20 SIM content and partnering with the neurology (pilot academic year [AY] 2020-2021) and pediatric clerkships (pilot AY 2021-2022) to deliver a facilitated one-hour ophthalmology workshop within each clerkship's didactic curriculum. We evaluated the tool using pre- and post-surveys and knowledge assessments. Of 80 IM residents, 33 (41.3%) completed the needs assessment. Of the 25 residents who attended the workshop, 23 (92.0%) completed the exit survey. IM residents reported discomfort in several ophthalmology domains (9 of 14 rated mean score < 3.0), confirming a need. Most (n = 21/23, 91.3%) rated the tool as good/excellent. Of 145 neurology clerkship students, 125 (86.2%) and at least 88 (60.7%) students completed the pre- and post-test/exit surveys, respectively. On average, participants highly rated the tool, perceiving 20/20 SIM to be relevant to their education [4.1 (0.8)]. Mean pre- to post-test knowledge scores increased from 7.5 to 8.5/10.0 points (p < 0.001). Of the 136 pediatric clerkship students, 67 (49.3%) and 51 (37.5%) completed the pre- and post-surveys, respectively. Respondents perceived increased comfort with ophthalmology topics after the facilitated workshop [3.8 (0.8)]. Mean pre- to post-test knowledge scores trended from 1.8 to 2.0/5.0 points (p = 0.30). Collectively, 20/139 (14.4%) of exit survey respondents visited www.2020sim.com within 1 month after the workshop. After identifying areas of greatest need with residents, we partnered with core clerkships to deliver cross-disciplinary ophthalmology content in UME. We found high engagement with 20/20 SIM, with trends toward increased knowledge.


Operative treatment of acute acromioclavicular joint injuries graded Rockwood III and IV: risks and benefits in tight rope technique vs. k-wire fixation.
Operative treatment of acromioclavicular joint injuries is recommended for higher degree dislocations. Recently a new option has become available with the minimally-invasive tight rope technique. Whereas clinical studies justify the medical use, risks and benefits remain unclear. Therefore, this study analyzed these facts associated with this procedure and compared them to K-wire fixation. A retrospective analysis was performed of patients surgically treated either with the TightRope™-technique (TR) or K-wires (KW) for a first event isolated Rockwood type III or higher acromioclavicular joint dislocation between 2004 and 2011. Timing for surgery, surgical duration, length of hospital stay, costs, complications and outpatient visits were recorded. 41 patients were included (TR: n = 18; KW: n = 23) with comparable demographics and injury severity. A trend towards shorter operation time was seen in the TR group (TR: 64.3 ±19.8 min. vs. KW: 80.9 ±33.7 min., n.s.) A tendency for lower total operation theater costs was seen in the TR group (TR: 474 ±436.5€ vs. KW: 749.1 ±31.2€, n.s.). Patients from the TR group left hospital earlier (TR: 2 ±1d vs. KW: 3.6 ±1.8d, p = 0.002). Severe complications (i.e. a fracture of the clavicle or nerve damage) occurred in neither of the groups. Early loss of reduction (n = 1) and impaired wound healing (n = 2) was seen in the TR group. Migrating K-wires (n = 4), loss of reduction (n = 1) and impingement syndrome (n = 1) were recorded in the KW group. Usage of the tight rope technique offered advantages, such as being a safe minimally-invasive technique and showed a tendency towards shorter operation time, and lower physician- and total operation and theater costs. Material costs were significantly higher for this device but patients were discharged earlier. The influence of different clinical long-term results on the financial outcome needs to be evaluated in further studies.


A paired case-control comparison of ziprasidone on visual sustained attention and visual selective attention in patients with paranoid schizophrenia.
Cognitive impairment is one of the main targets of the treatment to schizophrenia.The atypical antipsychotic was proved to improve the cognition function of the patients. There were a few of clinical trials to detect the effect of medicine treatment on attention function. But the respective changes of sustained and selective attention in the patients with treatment of ziprasidone were rarely investigated. This present study was to explore the effect of ziprasidone on visual sustained and selective attention in schizophrenia. There were 81 patients who were treated with ziprasidone and matched with 81 healthy controls in this open-label trial. The functions were evaluated by Continuous Performance Test (CPT) and Color Word Test (CWT) at baseline and eight weeks later. Between two groups the functions were compared at the two time points, and in patients group those were compared prior to and post treatment. As compared with healthy controls, the functions of the patients were worse. But after 8 weeks treatment of ziprasidone the functions improved in some degree, which were indicated by the change of CPT and CWT indexes. Furthermore, those of patients post treatment were better than prior to treatment. Patients with paranoid schizophrenia have visual sustained and selective attention deficits. The deficits can be improved partly with ziprasidone treatment.


A rheostat sets B-cell receptor repertoire selection to distinguish self from non-self.
In bone marrow VDJ-recombination continuously generates original repertoires of immature B cells expressing IgM-B cell receptor (BcR), in which each cell recognizes the wide variety of self and non-self antigens with an individually different spectrum of avidities. High avidity self-reactive B cells try to edit their BcRs by secondary or multiple VL-rearrangements to JL-rearrangements. If they do not manage to change their self reactivity, they are deleted by apoptosis. Low avidity self-reactive B cells are anergized, while B cells with no avidity to self are ignored. A rheostat crosslinking antigen-binding BcRs, self antigen complexed with pentameric IgM and Fcμ-receptor monitors high, low or no binding. PI3K and PTEN are the effectors of this self antigen-sensing device. In mature B cells this rheostat continues to function in the activation of resting B cells by foreign antigens which crosslink BcR, antigen and pentameric IgM with Fcμ-receptors.


Cath-DM-NT, a peptide derived from the skin of Duttaphrynus melanostictus, shows dual lectin-like and antioxidant activity.
Chansu, a mixture extracted from Duttaphrynus melanostictus or Bufo gargarizans Cantor, is a traditional Chinese medicine with a broad range of medical applications. However, the peptides/proteins in it have not received adequate attention. Herein, a Cathelicidin-DM-derived peptide named Cath-DM-NT was identified from the skin of D. melanostictus. Previous studies have shown that Cathelicidin-DM has significant antibacterial activity, while Cath-DM-NT has no antibacterial activity. In this study, Cath-DM-NT is found to have lectin-like activity which can agglutinate erythrocytes and bacteria, and bind to lipopolysaccharide (LPS). In addition, Cath-DM-NT has antioxidant activity, which can scavenge 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), 1,1-diphenyl-2-picrylhydrazyl (DPPH), and nitric oxide (NO) radicals and reduce Fe3+. Consistently, Cath-DM-NT can protect PC12 cells from H2O2-induced oxidative damage and carrageenan-induced paw edema, reduce malondialdehyde (MDA) and reactive oxygen species (ROS) accumulation, and restore superoxide dismutase (SOD) and glutathione (GSH) levels. Our study suggests that Cath-DM-NT can serve as a lead compound for the development of drugs with dual lectin and antioxidant effects.


School-Based Health Centers in the United States: Roots, Reality, and Potential.
Given the amount of time children and adolescents spend in school, these locations may be ideal for simultaneously supporting young people's health and academic achievement. School-based health centers (SBHCs) not only bring care to students in accessible and familiar locations, these centers also provide guidance for young people during a life stage when they are establishing lifelong health behavior habits. This article examines the literature exploring the impact of SBHCs from the perspective of multiple stakeholder groups including students, guardians, school personnel, community members, providers, hospital administrators, public health officials, and insurers. Studies describe the positive effects of SBHCs on students' health and educational outcomes. SBHCs are generally associated with decreased health care disparities among students, accelerated treatment, and increased school attendance. Additional research exploring strategies for optimizing SBHC's economic efficiency and tailoring SBHC services to meet the needs of vulnerable patient populations is essential. Investigation into the impacts of SBHCs on community stakeholders outside of the student population is also vital.


Strategies in stable ischemic heart disease: lessons from the COURAGE and BARI-2D trials.
There is a continuing debate regarding the most effective strategy for treating stable ischemic heart disease (SIHD). Conflicting data have emerged from several small, randomized controlled trials and meta-analyses regarding the benefits of early revascularization in SIHD. Two recent multicenter, randomized trials, the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial and the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI-2D) trial, compared two management strategies in SIHD-an initial conservative approach with optimal medical therapy (OMT) versus a strategy of early revascularization in combination with OMT. COURAGE randomized SIHD patients who were candidates for percutaneous coronary intervention (PCI) to either a strategy of early PCI in combination with OMT or OMT alone, whereas BARI-2D randomized diabetic patients with coronary artery disease to either early revascularization (PCI or coronary artery bypass surgery [CABG]) versus OMT. This review examines the principal findings of these trials, with discussion of their strengths, limitations, and applicability to the general population. The results support the hypothesis that in patients with SIHD, early revascularization with PCI in combination with OMT is not superior to OMT alone in reducing mortality and other major cardiovascular events. Subset analysis from BARI-2D did suggest that early CABG, although it did not reduce mortality, significantly reduced the rate of nonfatal myocardial infarction compared with an initial OMT approach. Based on these data, the majority of patients with SIHD should be managed initially with medical therapy, a strategy that is also the most cost effective. Revascularization can be considered for patients with severe or refractory symptoms despite a trial of medical therapy. For diabetic patients who have extensive coronary artery disease, early revascularization with CABG may be reasonable.


Missing Cells-A Rare Case of Persisting Thrombocytopenia in Pregnancy With Dengue and Role of Romiplostim in These Cases.
Dengue cases in pregnancy have high morbidity and mortality. More so if it leads to immune thrombocytopenic purpura which causes a drastic decrease in platelet, increasing chances of bleeding and mortality and pregnancy itself being a state of hemodynamic instability. Here, we present a case of dengue causing secondary immune thrombocytopenia. Managing these cases is challenging and need a multidisciplinary approach and should be done at a higher center. In previous reports, thrombocytopenia in such cases responded to steroids or IVIG. But in our case patient did not respond to either of them but to Romiplostim. There are only a few studies on the use of Romiplostim in dengue and dengue induced ITP and more study is required. Dengue induced persistent thrombocytopenia is rare but should always be kept in mind in managing these cases.


Sox9 overexpression in uterine epithelia induces endometrial gland hyperplasia.
SOX9 is a high mobility group transcription factor that is required in many biological processes, including cartilage differentiation, endoderm progenitor maintenance, hair differentiation, and testis determination. SOX9 has also been linked to colorectal, prostate, and lung cancer. We found that SOX9 is expressed in the epithelium of the adult mouse and human uterus, predominantly marking the uterine glands. To determine if SOX9 plays a role in the development of endometrial cancer we overexpressed Sox9 in the uterine epithelium using a progesterone receptor-Cre mouse model. Sox9 overexpression in the uterine epithelium led to the formation of simple and complex cystic glandular structures in the endometrium of aged-females. Histological analysis revealed that these structures appeared morphologically similar to structures present in patients with endometrial hyperplastic lesions and endometrial polyps that are thought to be precursors of endometrial cancer. The molecular mechanisms that cause the glandular epithelium to become hyperplastic, leading to endometrial cancer are still poorly understood. These findings indicate that chronic overexpression of Sox9 in the uterine epithelium can induce the development of endometrial hyperplastic lesions. Thus, SOX9 expression may be a factor in the formation of endometrial cancer.


Enhancing safety and outcomes with the newer antithrombotic and antiplatelet agents.
Novel antithrombotic and antiplatelet agents may help reduce the short-term risk of ischemic complications and the long-term risk of restenosis in patients undergoing coronary revascularization procedures. Recent clinical trials suggest that, compared with heparin, direct thrombin inhibitors (such as hirudin and hirulog) offer a predictable dose-response effect on the activated partial thromboplastin time without a concomitant increase in bleeding. Among the newer antiplatelet agents, the platelet integrin glycoprotein IIb/IIIa inhibitors (including c7E3 Fab and Integrelin) have generated the greatest interest. Clinical trial data have shown that c7E3 Fab (administered in conjunction with heparin) significantly reduces ischemic events and improves clinical outcomes. In phase II trials, Integrelin has also shown similar effects. The primary limitations have been an increase in heparin-associated bleeding, which suggests that the safety profile may be enhanced by careful adjustment of the heparin dose implementation of other patient management guidelines. The safety and efficacy data obtained in future trials should shed more light on the appropriate roles of these drugs in interventional cardiology.


Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line.
Increasing incidence of various cancers has been reported in diabetic patients. O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. However, the mechanisms by which O-GlcNAcylation promotes tumor growth remain unclear. Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. Results revealed that treatment with Thiamet G (TMG), an inhibitor of O-GlcNAc hydrolase, increased both anchorage-dependent and -independent growth of the cells. O-GlcNAc transferase overexpression also increased the growth. These treatments increased AMPK O-GlcNAcylation in a dose-dependent manner, which led to reduced AMPK phosphorylation and mTOR activation. Chemical inhibition or activation of AMPK led to increased or decreased growth, respectively, which was consistent with the data with genetic inhibition of AMPK. In addition, TMG-mediated acceleration of tumor growth was abolished by both chemical and genetic inhibition of AMPK. To examine the effects of AMPK O-GlcNAcylation in vivo, the LoVo cells were s.c. transplanted onto the backs of BALB/c-nu/nu mice. Injection of TMG promoted the growth and enhanced O-GlcNAcylation of the tumors of the mice. Consistent with in vitro data, AMPK O-GlcNAcylation was increased, which reduced AMPK phosphorylation and resulted in activation of mTOR. Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR.


The Zürich amygdalo-hippocampectomy series: a short up-date.
Selective amygdalohippocampectomy was developed as a surgical treatment for temporal lobe epilesy with a well-defined unilateral mesiobasal limbic seizure onset. Since 1975, 236 patients have been operated on in Zürich. We briefly summarize recent studies on the seizure outcome with analysis of the postoperative long-term fluctuations in relation to postoperative anticonvulsant drug treatment, on the underlying neuropathology, and on the relationships between magnetic resonance scanning estimates of total volume of the removed tissue and the resection scores of amygdala, hippocampus and parahippocampus gyrus.


Perampanel: A Review in Drug-Resistant Epilepsy.
Perampanel (Fycompa®), an orally-active, selective, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, is a first-in-class antiepileptic drug (AED) offering the convenience of once-daily administration. In the EU and US, perampanel is approved in patients with epilepsy aged ≥12 years for the adjunctive treatment of primary generalized tonic-clonic seizures (GTCS) and partial-onset seizures (POS; with or without secondary generalization). In phase III trials of 17 or 19 weeks' duration, add-on perampanel ≤12 mg/day significantly improved seizure control in patients aged ≥12 years who were experiencing either primary GTCS or POS (with or without secondary generalization), despite ongoing treatment with stable dosages of one to three AEDs. Improvements in seizure control were maintained for up to 2 years in extensions of these core studies. Perampanel also provided sustained seizure control for up to ≈4 years in an extension of two phase II studies in patients aged ≥18 years with drug-resistant POS. Adjunctive perampanel therapy was generally well tolerated. Treatment-emergent adverse events were most commonly CNS-related (e.g. dizziness, somnolence, fatigue and irritability) and dose-related; however, most were of mild to moderate intensity. Clinical experience with perampanel is accumulating, although comparative studies and pharmacoeconomic data that could assist in positioning it relative to other AEDS that are approved and/or recommended as adjunctive therapy are lacking. Nonetheless, on the basis of its overall clinical profile and unique mechanism of action, perampanel is a useful additional adjunctive treatment option for patients with drug-resistant POS, with or without secondary generalization, and primary GTCS.


Design, synthesis and antimicrobial evaluation of novel 2-aryl-thiazolidin-4-one derivatives.
Novel 2-arylthiazolidin-4-one derivatives (8a-q and 11) have been synthesized in good-to-excellent yields (70-96%) by one-pot three-component condensation-cyclization reaction of aromatic or aliphatic primary amines, aromatic aldehydes, and thioglycolic acid in polypropylene glycol at 110°C temperature. The in vitro antimicrobial activity of the synthesized 2-arylthiazolidin-4-ones was investigated against a panel of six pathogenic fungal strains, a Gram-positive and three Gram-negative bacteria. Results revealed that the compounds (8a-d) bearing 3-(4-(1H-imidazolylmethyl)phenyl)-substituent displayed significant antibacterial efficacy specifically against Klebsiella pneumoniae (minimum inhibitory concentration 12.5 μg/mL). In addition, some of the synthesized compounds have also shown antimicotic activity against Sporothrix schenckii, Trichophyton mentagrophytes, and Aspergillus fumigatus at the concentration of 50 μg/mL.


Neonatal sepsis and simple minor neurological dysfunction.
This study examined potential risk factors for and consequences of simple minor neurological dysfunction (SMND), in a group of very low-birthweight newborns followed until preschool age. This was a prospective longitudinal study. Children with birthweight <1500 g were assessed at 4-6 years of age. Twenty-eight children with normal neurological examination and 35 children with SMND were included in the final analysis. Risk factors for the development of SMND and its association with certain neuropsychiatric conditions were studied. Based on neonatal data, in children with SMND, Apgar score at 1 min (6.13 ± 2.37 vs 7.66 ± 1.04, P = 0.008) and at 5 min (8.63 ± 1.29 vs 9.45 ± 0.65, P = 0.019) was lower, duration of hospital stay was longer (45.8 ± 21.8 vs 35.1 ± 18.2 days, P = 0.037), and the frequency of sepsis was higher (73.5 vs 25%, P < 0.001). Sepsis was found to be an independent risk factor for SMND (OR, 7.6; 95% CI: 2.2-26.0; P = 0.001). The children with SMND had lower intelligence quotient and higher prevalence of hyperactivity and refraction error. Postnatal sepsis was the single most important risk factor for the development of SMND, and these children with SMND are at great risk for certain neuropsychiatric conditions. Preventive strategies, particularly for sepsis in the neonatal period, and early diagnosis and rehabilitation of future neuropsychiatric disorders are needed for better management of these cases.


Development of a Temperate Climate-Adapted indica Multi-stress Tolerant Rice Variety by Pyramiding Quantitative Trait Loci.
Successful cultivation of rice (Oryza sativa L.) in many Asian countries requires submergence stress tolerance at the germination and early establishment stages. Two quantitative trait loci, Sub1 (conferring submergence tolerance) and AG1 (conferring anaerobic germination), were recently pyramided into a single genetic background, without compromising any desirable agronomic traits, leading to the development of Ciherang-Sub1 + AG1 (CSA). However, little research has been conducted to enhance plant tolerance to abiotic stress (submergence) and biotic stress (rice blast), which occur in a damp climate following flooding. The BC2F5 breeding line was phenotypically characterized using the AvrPi9 isolate. The biotic and abiotic stress tolerance of selected lines was tested under submergence stress and anaerobic germination conditions, and lines tolerant to each stress condition were identified through phenotypic and gene expression analyses. The Ciherang-Sub1 + AG1 + Pi9 (CSA-Pi9) line showed similar agronomic performance to its recurrent parent, CSA, but had significantly reduced chalkiness in field trials conducted in temperate regions. Unexpectedly, the CSA-Pi9 line also showed salinity tolerance. Thus, the breeding line newly developed in this study, CSA-Pi9, functioned under stress conditions, in which Sub1, AG1, and Pi9 play a role and had superior grain quality traits compared to its recurrent parent in temperate regions. We speculate that CSA-Pi9 will enable the establishment of climate-resilient rice cropping systems, particularly in East Asia.


The duality of STAT2 mediated type I interferon signaling in the tumor microenvironment and chemoresistance.
The tumor microenvironment consists of tumor cells, extracellular matrix, blood vessels, and non-tumor cells such as fibroblasts and immune cells. Crosstalk among components of this cellular ecosystem can transform non-malignant cells and promote tumor invasion and metastasis. Evidence is accumulating that the transcription factor STAT2, a downstream effector of type I interferon (IFN-I) signaling, can either inhibit or promote tumorigenesis depending on the unique environment presented by each type of cancer. STAT2 has long been associated with the canonical JAK/STAT pathway involved in various biological processes including reshaping of the tumor microenvironment and in antitumor immunity. This dichotomous tendency of STAT2 to both inhibit and worsen tumor formation makes the protein a curious, and yet relatively ill-defined player in many cancer pathways involving IFN-I. In this review, we discuss the role of STAT2 in contributing to either a tumorigenic or anti-tumorigenic microenvironment as well as chemoresistance.


Psychometric evaluation of the Swallowing Outcomes After Laryngectomy (SOAL) patient-reported outcome measure.
The purpose of this study was to evaluate the psychometric properties of the Swallowing Outcomes After Laryngectomy (SOAL) in a large group of people who underwent a laryngectomy. We conducted a cross-sectional psychometric study of laryngectomy patients (minimum 3 months posttreatment) attending routine hospital follow-up for the psychometric evaluation of SOAL. One hundred ten people participated in this study. Thirteen percent of the patients had a laryngectomy, 63% had laryngectomy with radiotherapy, and 24% had laryngectomy with chemoradiation therapy. The SOAL showed good quality of data (minimal missing data and floor effects); good internal consistency (α = 0.91); and adequate test-retest reliability (intra-class correlation coefficient = 0.73). In terms of validity, it differentiated people by treatment group (F(2,85) = 8.02; p = .001) and diet texture group (t(102) = -7.33; p < .001). The SOAL demonstrates good validity and has potential for use in research. Further study is required to determine its clinical application. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1639-E1645, 2016.


Does the addition of post-operative gabapentin reduce the use of narcotics after orthopedic surgery?
To evaluate the efficacy of post-operative gabapentin administration as an analgesic agent and its effect on narcotic use after orthopedic surgery in an outpatient sports medicine practice by comparing patients prior to and after initiating the routine use of gabapentin as part of a standardized post-operative pain medication regimen. We hypothesized that adding gabapentin to a multimodal post-operative pain regimen would decrease the number of requested pain medication refills and have no detrimental effect on Visual Analogue Scale and Single Assessment Numerical Evaluation scores at these early post-operative visits. All outpatient surgical patients, <90 years of age, undergoing outpatient orthopedic surgery by the study's senior author were included between 08/05/2021 and 02/22/2022. Patients were allowed 1 narcotic refill post-operatively and only in the first 3 weeks. The primary outcome was difference in percentage of patients who requested a narcotic refill within 3 weeks post-op. Two- and 6-week Visual Analogue Scale and Single Assessment Numerical Evaluation scores, and baseline health and demographic data. T-tests were run on continuous variables, Chi-Square or Fisher's Exact Test were run on dichotomous variables, and Mann-Whitney U test was run on all other categorical variables. Statistical significance was set at P < .05 for all tests. There was a significant difference in narcotic refills at 3 weeks: 23 pre-gabapentin patients and 9 post-gabapentin patients (22.8% vs 9.0%, respectively: P = .006). There were no differences between 2- and 6-week Visual Analogue Scale and 2-week Single Assessment Numerical Evaluation scores. There was a significant difference in 6-week SANE between groups: mean difference = 6.4 (P = .027) though less than the established MCID. Addition of gabapentin to a post-operative multimodal pain regimen reduced the use of narcotics after orthopedic sports medicine surgeries while also providing equivalent pain control.


An Analysis of Interns' Feedback after Dermatology Posting.
Dermatology knowledge among fresh medical graduates is poor in India as undergraduate medical curriculum and Internship training lack adequate focus on this subject. This contributes to the inappropriate management of Dermatology patients by the medical graduates. To analyse the expectations, motivations and experience of interns during their dermatology posting. This was a retrospective record review of questionnaire-based anonymous validated feedback forms submitted by interns posted in a dermatology department of a tertiary care institute. The feedback form contained nine multiple choice questions some of which allowed multiple responses. A total of 63 completed forms were analysed. The common expectations before the posting were, to learn the management of basic dermatological problems (98.4%), to take an informed decision regarding post-graduation in dermatology (53.9%) and hope that the posting will be useful for the postgraduate entrance test (50.7%). After the posting, 69.87% of them felt that their expectations were fulfilled. After the posting, 84.1% of the interns felt that they would have liked to study dermatology as a separate undergraduate subject with a summative assessment at the end. The sample size was less and the feedback form contained limited questions. The majority of the interns were satisfied after dermatology posting. Increased exposure of interns to dermatology inpatients and side laboratory procedures will further enrich their clinical experience. The inclusion of dermatology as a separate subject with examination in the undergraduate curriculum was a felt need.


Customized implant abutments: technical notes.
Custom-fabricated angulated abutments can be of value when implant angulation or position jeopardizes esthetics and/or function and makes retrievability difficult. A wax pattern is prepared over a castable pattern or gold cylinder. After the casting is completed, a secondary screw channel is created in the angulated abutment to retain the superstructure and the definitive prosthesis. The rationale for the use of customized angulated abutments is described. Technical procedures are presented that allow for modifications of individual cases.


A Depression Prevention Intervention for Adolescents in the Emergency Department.
To evaluate acceptability and feasibility of a theoretically based two-part (brief in-person + 8-week automated text message) depression prevention program, "intervention for DepressiOn and Violence prevention in the Emergency department" (iDOVE), for high-risk adolescents. English-speaking emergency department (ED) patients (age 13-17, any chief complaint) were sequentially approached for consent on a convenience sample of shifts and screened for inclusion based on current depressive symptoms and past-year violence. After consent, baseline assessments were obtained; all participants were enrolled in the two-part intervention (brief in-ED + 8-week two-way text messaging). At 8 weeks, quantitative and qualitative follow-up assessments were obtained. Measures included feasibility, acceptability, and preliminary data on efficacy. Qualitative data were transcribed verbatim, double coded, and interpreted using thematic analysis. Quantitative results were analyzed descriptively and with paired t tests. As planned, 16 participants (eight each gender) were recruited (75% of those who were eligible; 66% nonwhite, 63% low income, mean age 15.4). The intervention had high feasibility and acceptability: 93.8% completed 8-week follow-up; 80% of daily text messages received responses; 31% of participants requested ≥1 "on-demand" text message. In-person and text message portions were rated as good/excellent by 87%. Qualitatively, participants articulated: (1) iDOVE was welcome and helpful, if unexpected in the ED; (2) the daily text message mood assessment was "most important"; (3) content was "uplifting"; and (4) balancing intervention "relatability" and automation was challenging. Participants' mean ΔBDI-2 (Beck Depression Inventory) from baseline to 8-week follow-up was -4.9, (p = .02). This automated preventive text message intervention is acceptable and feasible. Qualitative data emphasize the importance of creating positive, relevant, and interactive digital health tools for adolescents.


Tuning electron delocalization of hydrogen-bonded organic framework cathode for high-performance zinc-organic batteries.
Stable cathodes with multiple redox-active centres affording a high energy density, fast redox kinetics and a long life are continuous pursuits for aqueous zinc-organic batteries. Here, we achieve a high-performance zinc-organic battery by tuning the electron delocalization within a designed fully conjugated two-dimensional hydrogen-bonded organic framework as a cathode material. Notably, the intermolecular hydrogen bonds endow this framework with a transverse two-dimensional extended stacking network and structural stability, whereas the multiple C = O and C = N electroactive centres cooperatively trigger multielectron redox chemistry with super delocalization, thereby sharply boosting the redox potential, intrinsic electronic conductivity and redox kinetics. Further mechanistic investigations reveal that the fully conjugated molecular configuration enables reversible Zn2+/H+ synergistic storage accompanied by 10-electron transfer. Benefitting from the above synergistic effects, the elaborately tailored organic cathode delivers a reversible capacity of 498.6 mAh g-1 at 0.2 A g-1, good cyclability and a high energy density (355 Wh kg-1).


Day-3 embryo metabolomics in the spent culture media is altered in obese women undergoing in vitro fertilization.
To determine whether the global metabolomic profile of the spent culture media (SCM) of day-3 embryos is different in obese and normoweight women undergoing in vitro fertilization (IVF). Prospective cohort analysis. IVF clinic. Twenty-eight young, nonsmoking women with normoweight, nonsmoking male partners with mild/normal sperm factors undergoing a first IVF attempt for idiopathic infertility, tubal factor infertility, or failed ovulation induction: obese ovulatory women (n = 12); obese women with polycystic ovary syndrome (PCOS; n = 4); normoweight ovulatory women (n = 12). Fifty μl of SCM collected from two day-3 embryos of each cohort. Metabolomic profiling via ultrahigh performance liquid chromatography coupled to mass spectrometry of SCM from a total of 56 embryos. The untargeted metabolomic profile was different in obese and normoweight women. Partial least squares discriminant analysis resulted in a clear separation of samples when a total of 551 differential metabolites were considered. A prediction model was generated using the most consistent metabolites. Most of the metabolites identified were saturated fatty acids, which were detected in lower concentrations in the SCM of embryos from obese women. The metabolomic profile was similar in obese women with or without PCOS. The metabolomic profile in the SCM of day-3 embryos is different in normoweight and obese women. Saturated fatty acids seem to be reduced when embryos from obese patients are present. NCT01448863.


Mutations in topA interfere with the inducible expression of DNA damage response loci in Salmonella typhimurium.
Strains of Salmonella typhimurium deficient in topoisomerase I activity (topA mutants) are UV sensitive and non-mutable (Overbye and Margolin: J Bacteriol 146:170-178, 1981). Using lac-operon fusions to DNA damage inducible (din) loci we investigated whether these observations could be explained by an inability of topA strains to efficiently induce DNA damage responses. Mitomycin C (MMC)-induced expression of lac-operon fusions to uvrB and to a second SOS locus, din-9, was largely eliminated in topA bacteria. The inducible expression of several other din-fusions was also diminished. This inducibility defect was mimicked by growth of din-9 topA+ bacteria in media of high osmolarity, a condition that leads to increased DNA supercoiling. Inhibitors of DNA gyrase efficiently induced din-9 in topA bacteria. Together, these results suggest that the topA effect on din expression may be mediated at the level of DNA supercoiling. The sensitivities of a number of din-fusions to topA paralleled the degree to which they were repressed by excess LexA, suggesting that mutations in topA might influence LexA-operator interactions and/or increase lexA expression.


Deviation Management: Key Management Subsystem Driver of Knowledge-Based Continuous Improvement in the Henry Ford Production System.
To develop a business subsystem fulfilling International Organization for Standardization 15189 nonconformance management regulatory standard, facilitating employee engagement in problem identification and resolution to effect quality improvement and risk mitigation. From 2012 to 2016, the integrated laboratories of the Henry Ford Health System used a quality technical team to develop and improve a management subsystem designed to identify, track, trend, and summarize nonconformances based on frequency, risk, and root cause for elimination at the level of the work. Programmatic improvements and training resulted in markedly increased documentation culminating in 71,641 deviations in 2016 classified by a taxonomy of 281 defect types into preanalytic (74.8%), analytic (23.6%), and postanalytic (1.6%) testing phases. The top 10 deviations accounted for 55,843 (78%) of the total. Deviation management is a key subsystem of managers' standard work whereby knowledge of nonconformities assists in directing corrective actions and continuous improvements that promote consistent execution and higher levels of performance.


What is the impact of personal care products selection on greywater characteristics and reuse?
Accounting for up to three quarters of the wastewater volume resulting from domestic activities but containing only a third of its organic content, greywater is seen as an alternative water source for non-potable reuse. This unique study explores the question whether consumers' product selection could affect the treatability and reuse of bathroom greywater. Fifty five personal care and household products (PCHP) were analysed for their effects on a range of water quality parameters including their aquatic and soil toxicity using Microtox® and MicroResp™. The organic content of these PCHPs varied considerably, not only from one category to another (0.2 gTOC.L-1 for hair conditioners to 2.7 gTOC.L-1 for toothpastes), but also within each category (0.1 gTOC.L-1 to 3.6 gTOC.L-1 amongst the shampoos). As expected, the PCHPs' macronutrient content was low, suggesting some limitation towards biological treatment of bathroom greywater. Regarding the impact of product selection on toxicity towards aquatic and soil microorganisms, the results revealed a higher sensitivity of Vibrio fischeri to the individual PCHPs than the MicroResp™ soil microorganisms. In the latter case, 75% of the products caused a stimulation response from the microorganisms although some decreases in basal respiration were observed for specific PCHPs within product categories. However, based solely on MicroResp™, the short-term discharge of treated bathroom greywater, regardless of consumer product selection, is unlikely to have a negative impact on soil microbial activity. Overall, the work has demonstrated the importance of consumer choice on the pollution load and treatability of greywater. However, no clear link between greywater characteristics and factors that normally determine consumer product selection (branding, type) were identified. This means it is not currently possible for consumers to actively manage the issue through choice such that process designers and technology developers must ensure technologies are sufficiently robust to manage the potential variations that could occur.


Carotenoid and polyphenol bioaccessibility and cellular uptake from plum and cabbage varieties.
Plum and cabbage are rich in carotenoids and polyphenols. However, their bioactivity depends on their release and intestinal uptake. Four varieties of Brassicaceae (Duchy, Scots Kale, Kale, Kalorama) and Prunus (Cherry Plum, Plum 620, Ersinger, Italian Plum) were studied; bioaccessibility following in vitro digestion, cellular uptake (Caco-2 vs. co-culture cell model: Caco-2:HT-29-MTX (90:10%) and colonic fermentation were determined for carotenoids/polyphenols; the influence of certain kitchen preparations was likewise studied. Carotenoids were non-significantly influenced by the latter, while for polyphenols, boiling and steaming significantly reduced total phenolics (p<0.05). Carotenoid bioaccessibility did not differ significantly between Prunus vs. Brassicaceae varieties, but xanthophyll was higher than carotene bioaccessibility (p<0.01). Polyphenol bioaccessibility was low (<10%), possibly compromised by the cream containing test meal. Total carotenoid cellular uptake varied between varieties (0.3-4.1%), being higher for carotenes (4.1%) than for xanthophylls (1.6%, p<0.01), and were higher for the co-culture cell model compared to Caco-2 cells (p<0.01). Total carotenoid recovery in the colonic fraction varied from 4% to 25%. Lower bioaccessibility of carotenes thus appeared to be somewhat counterbalanced by higher cellular uptake. The potential positive role of the mucus layer for cellular uptake and the fate of the colonic digesta deserve further attention in the future.


Abnormal "hair-like" filaments in chronic maxillary sinusitis . A scanning electron microscopic investigation.
Scanning electron microscopic investigations were performed on the maxillary sinus mucosa of five healthy persons and seven patients with chronic maxillary sinusitis. The occurrence of previously undescribed hair-like filaments in one case of chronic maxillary sinusitis is presented. These abnormal filaments are much longer (about 50--60 micron) and thinner (about 0.08 micron) than normal kinocilia (about 0.2 micron thick and 5--7 micron long), thus exhibiting a hair-like appearance. As the microvilli (cytofila) in maxillary sinus mucosa have the same thickness (about 0.08 micron), these hair-like filaments could be regarded as abnormally long microvilli. The possible significance of these abnormal filaments is discussed.


[Studies on biomechanics of human foot: a review].
The plantar pressure and shear force measurement, the function and effect of joints, bones and ligaments of foot during running and walking, and the modeling and finite element analysis of human foot are three important aspects in biomechanical study of foot. They are also the basis of the study of rehabilitation. In this paper, studies on the three aspects are reviewed, and further promising developments are proposed.


Physiological responses of pumpkin to zinc oxide quantum dots and nanoparticles.
The present study investigated that the potential of soil or foliar applied 15 mg/L zinc oxide quantum dots (ZnO QD, 11.7 nm) to enhance pumpkin (Cucurbita moschata Duch.) growth and biomass in comparison with the equivalent concentrations of other sizes of ZnO particles, ZnO nanoparticles (ZnO NPs, 43.3 nm) and ZnO bulk particles (ZnO BPs, 496.7 nm). In addition, ZnSO4 was used to set a Zn2+ ionic control. For foliar exposure, ZnO QD increased dry mass by 56% relative to the controls and values were 17.3% greater than that of the ZnO NPs particles. The cumulative water loss in the ZnO QD treatment was 10% greater than with ZnO NPs, suggesting that QD could better enhance pumpkin growth. For the root exposure, biomass and accumulative water loss equivalent across all Zn treatments. No adverse effects in terms of pigment (chlorophyll and anthocyanin) contents were evident across all Zn types regardless exposure routes. Foliar exposure to ZnO QD caused 40% increases in shoot Zn content as compared to the control; the highest Zn content was evident in the Zn2+ ionic treatment, although this did not lead to growth enhancement. In addition, the shoot and root content of other macro- and micro-nutrients were largely equivalent across all the treatments. The contents of other nutritional compounds, including amino acids, total protein and sugar, were also significantly increased by foliar exposure of ZnO QD. The total protein in the ZnO QD was 53% higher than the ZnO particle treatments in the root exposure group. Taken together, our findings suggest that ZnO QDs have significant potential as a novel and sustainable nano-enabled agrichemical and strategies should be developed to optimize benefit conferred to amended crops.


Merging nano-genotoxicology with eco-genotoxicology: an integrated approach to determine interactive genotoxic and sub-lethal toxic effects of C(60) fullerenes and fluoranthene in marine mussels, Mytilus sp.
Whilst there is growing concern over the potential detrimental impact of engineered nanoparticles (ENPs) on the natural environment, little is known about their interactions with other contaminants. In the present study, marine mussels (Mytilus sp.) were exposed for 3 days to C(60) fullerenes (C(60); 0.10-1 mg l(-1)) and a model polycyclic aromatic hydrocarbon (PAH), fluoranthene (32-100 μg l(-1)), either alone or in combination. The first two experiments were conducted by exposing the organisms to different concentrations of C(60) and fluoranthene alone, in order to determine the effects on total glutathione levels (as a measure of generic oxidative stress), genotoxicity (DNA strand breaks using Comet assay in haemocytes), DNA adduct analyses (using (32)P-postlabelling method) in different organs, histopathological changes in different tissues (i.e. adductor muscle, digestive gland and gills) and physiological effects (feeding or clearance rate). Subsequently, in the third experiment, a combined exposure of C(60) plus fluoranthene (0.10 mg l(-1) and 32 μg l(-1), respectively) was carried out to evaluate all endpoints mentioned above. Both fluoranthene and C(60) on their own caused concentration-dependent increases in DNA strand breaks as determined by the Comet assay. Formation of DNA adducts however could not be detected for any exposure conditions. Combined exposure to C(60) and fluoranthene additively enhanced the levels of DNA strand breaks along with a 2-fold increase in the total glutathione content. In addition, significant accumulation of C(60) was observed in all organs, with highest levels in digestive gland (24.90 ± 4.91μg C(60) g(-1) ww). Interestingly, clear signs of abnormalities in adductor muscle, digestive gland and gills were observed by histopathology. Clearance rates indicated significant differences compared to the control with exposure to C(60), and C(60)/fluoranthene combined treatments, but not after fluoranthene exposure alone. This study demonstrated that at the selected concentrations, both C(60) and fluoranthene evoke toxic responses and genetic damage. The combined exposure produced enhanced damage with additive rather than synergistic effects.


Caregiver burden, patients' self-perceived burden, and preference for palliative care among cancer patients and caregivers.
Recently, caregiver burden (CB) has emerged as an important issue in the area of palliative medicine. However, patients' feelings related to being a burden to their families (i.e., self-perceived burden [SPB]) is also a significant issue. We evaluated the relation of CB and SPB as preference for palliative care. A national, multicenter, cross-sectional survey of 326 patient-caregiver dyads was performed. A set of paired questionnaires evaluating CB and SPB (five domain items assessed on a four-point Likert scale) were independently administered to patients and their caregivers. Among the respondents, only the patients with distant stage cancer and their caregivers were included. Multivariate analyses were conducted to identify the associations between CB and SPB and preference for palliative care. Caregivers and patients who preferred palliative care to life sustaining treatment reported higher CB and SPB scores, respectively. Caregivers who felt more of a burden were more likely to prefer palliative care over life sustaining treatment for their patients (adjusted odds ratio [aOR] = 1.67, 95% CI: 1.21-2.31). In addition, patients who perceived their caregivers' burden as large tended to prefer palliative care (aOR = 1.61, 95% CI: 1.16-2.22). Both CB and SPB increased preference for palliative care. This could be interpreted that high CB can lead to preference for palliative care in both patients and their caregivers, potentially threatening patient autonomy. Efforts to relieve CB and SPB are needed.


Evidence-practice gap in minimal intervention dentistry: Findings from a dental practice-based research network.
This study aimed to 1) quantify the evidence-practice gap (EPG) between dental clinical practice and published evidence on Minimal Intervention Dentistry (MID) among dentists in Japan; and 2) examine the hypothesis that dentist characteristics have a significant association with the EPG. We conducted a cross-sectional study via use of a web-based questionnaire survey of dentists who were affiliated with the Dental Practice-based Research Network Japan (n = 297). To quantify the EPG on MID, we used a questionnaire that included 10 clinical questions or scenarios to assess concordance between dental practice and published evidence on MID. We evaluated concordance by coding responses to each question as consistent or inconsistent with the evidence. An overall concordance was then determined as percent of responses that were consistent with published evidence for 10 questions. Subsequently, multiple logistic regression analysis was conducted to examine the associations between dentist characteristics and higher overall concordance (≥median) with published evidence. Mean and median overall dentist-level concordance were both 60 % (SD: 18, interquartile range: 50-75 %). Logistic regression analysis showed that "gender of dentist", "city population", and "frequency of obtaining evidence from the scientific journal articles in English" were significantly associated with high concordance, with odds ratios (95 % CIs) of 2.33 (1.01-5.39), 2.01 (1.02-3.96), and 2.45 (1.08-5.59), respectively. Japanese dentists demonstrated medium concordance with published evidence, indicating that an EPG on MID exists in Japanese dental clinical practices. Dentist-specific characteristics had significant associations with high concordance with published evidence. Despite the establishment and dissemination of the concept of MID, the EPG on MID exists in Japanese dental clinical practices. A high concordance was significantly associated with the following dentist characteristics: "female dentist", "dental clinic location in a government-ordinance-designated city", and "frequently obtaining evidence from the English-language scientific journal articles".


Validity, reliability and minimal detectable change of Mini-BESTest Turkish version in neurological disorders.
It is aimed to investigate the psychometric properties of Mini-BESTestTR in Turkish patients with neurological disorders. A total of 61 people between the ages of 42 and 80, who were patients with Parkinson's disease, stroke or multiple sclerosis for more than 1 year, were included in the study. For inter-rater reliability, two independent researchers applied the scale two times within 5 days for test-retest reliability. The relationship of mini-BESTestTR with Berg Balance Scale (BBS) to assess concurrent validity, and Timed Get up and Go (TUG), Functional Reach Test (FRT) and Functional Ambulation Classification (FAC) for convergent validity was investigated. The scores of the two evaluators were within the range of agreement (mean = - 0.278 ± 1.484, p > 0.05), and the Mini-BESTestTR had excellent inter-rater reliability [ICC (95% CI) = 0.989 (0.981-0.993)] and test-retest reliability [ICC (95% CI) = 0.998 (0.996-0.999)]. Mini-BESTestTR had a strong correlation with BBS (r = 0.853, p < 0.001) and TUG (r = - 0.856, p < 0.001), had a moderate correlation with FAC (r = 0.696, p < 0.001) and FRT (r = 0.650, p < 0.001). Mini-BESTestTR showed significant correlations with other balance assessment measures, and concurrent and convergent validity of Mini-BESTestTR was demonstrated when administered to a sample of patients with chronic stroke, Parkinson's disease and multiple sclerosis.


Association between Long-Term Second Malignancy Risk and Radiation: A Comprehensive Analysis of the Entire Surveillance, Epidemiology, and End Results Database (1973-2014).
Second malignancies (SMs) after radiation therapy are rare but serious sequelae of treatment. This study investigates whether radiation therapy use is associated with changes in baseline SM risk. We extracted all patients with cancer, with or without SM, in the Surveillance, Epidemiology, and End Results database from 1973 to 2014. Cumulative incidence of SM for patients stratified by radiation therapy status was calculated using a competing risk model, both for the entire cohort and for subgroups based on the primary tumor's anatomic location. We identified 2,872,063 patients with cancer, including 761,289 patients who received radiation therapy and 2,110,774 who did not. The SM rate at 20 years for patients receiving radiation therapy versus no radiation therapy was 21.4% versus 18.8%. The relative risk for SM associated with radiation therapy for the overall group was 1.138 at 20 years. The relative risks for SM associated with radiation therapy to malignancies arising from central nervous system and orbits, head and neck, thorax, abdomen, and pelvis at 20 years were 0.704, 1.011, 0.559, 0.646, and 1.106 for men and 0.792, 1.298, 1.265, 0.780, and 0.988 for women, respectively. The association between SM and radiation therapy varies with both sex and disease anatomic location, with the largest increase in SM seen in females irradiated to the head and neck region. Overall, the absolute change in SM rates associated with radiation therapy remains small, with differences in various clinical contexts.


China can be self-sufficient in maize production by 2030 with optimal crop management.
Population growth and economic development in China has increased the demand for food and animal feed, raising questions regarding China's future maize production self-sufficiency. Here, we address this challenge by combining data-driven projections with a machine learning method on data from 402 stations, with data from 87 field experiments across China. Current maize yield would be roughly doubled with the implementation of optimal planting density and management. In the 2030 s, we estimate a 52% yield improvement through dense planting and soil improvement under a high-end climate forcing Shared Socio-Economic Pathway (SSP585), compared with a historical climate trend. Based on our results, yield gains from soil improvement outweigh the adverse effects of climate change. This implies that China can be self-sufficient in maize by using current cropping areas. Our results challenge the view of yield stagnation in most global areas and provide an example of how food security can be achieved with optimal crop-soil management under future climate change scenarios.


GePMI: A statistical model for personal intestinal microbiome identification.
Human gut microbiomes consist of a large number of microbial genomes, which vary by diet and health conditions and from individual to individual. In the present work, we asked whether such variation or similarity could be measured and, if so, whether the results could be used for personal microbiome identification (PMI). To address this question, we herein propose a method to estimate the significance of similarity among human gut metagenomic samples based on reference-free, long k-mer features. Using these features, we find that pairwise similarities between the metagenomes of any two individuals obey a beta distribution and that a p value derived accordingly well characterizes whether two samples are from the same individual or not. We develop a computational framework called GePMI (Generating inter-individual similarity distribution for Personal Microbiome Identification) and apply it to several human gut metagenomic datasets (>300 individuals and >600 samples in total). From the results of GePMI, most of the human gut microbiomes can be identified (auROC = 0.9470, auPRC = 0.8702). Even after antibiotic treatment or fecal microbiota transplantation, the individual k-mer signature still maintains a certain specificity.


Further study on the three-dimensional structure of the core of Marek's disease virus and herpesvirus of turkey.
Three-dimensional structures of the core of Marek's disease virus and herpesvirus of turkey were examined by the tilting apparatus of an electron microscope. Various types of the core found in the infected cells were considered to represent developmental stages of the viruses. The basic structure of the core consisted of a toroid surrounding a cylindrical mass, which was clearly demonstrated by tilting the core in two directions. A cylindrical mass spooled by more than two toroids, which seemed to constitute a spiral band of 10 to 20 nm, was demonstrated. The maturation process of the cores of the viruses was also discussed.


Author Correction: Vector compositions change across forested to deforested ecotones in emerging areas of zoonotic malaria transmission in Malaysia.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Antioxidant potential of Xylopia aethiopica fruit acetone fraction in a type 2 diabetes model of rats.
The fruit decoction of Xylopia aethiopica (Dunal) A. Rich. is widely used for the treatment of diseases associated with oxidative stress such as diabetes, particularly in Africa. The present study was aimed to investigate the effects of X. aethiopica fruit acetone (XAFA) fraction in ameliorating oxidative stress in a type 2 diabetes (T2D) model of rats. The crude X. aethiopica fruit ethanolic extract was fractionated using solvents with increasing polarity and acetone fraction showed significantly (p<0.05) higher in vitro antioxidant potentials which were measured by (1,1-diphenyl-2-picrylhydrazyl radical (DPPH), hydroxyl radical (HRS) and nitric oxide (NO) assays compared to other fractions. It was then subjected to in vivo antioxidant study in a T2D rat model. Acetone fraction depicted potent in vitro antioxidant actions (IC50: DPPH: 19.82±0.73μg/mL; HRS: 25.34±6.19μg/mL; NO: 14.45±2.44μg/mL) compared to other fractions. Additionally, a significant (p<0.05) and dose-dependent improvement on the in vivo antioxidant status was observed in the animals in diabetic treated groups (DXAL, DXAH) compared to the diabetic control (DBC) group. The results of our study suggest that XAFA possesses potent antioxidant potential and could be used to ameliorate oxidative stress associated metabolic complications such as T2D.


Corin deficiency impairs cardiac function in mouse models of heart failure.
Corin is a protease in the natriuretic peptide system. Deleterious CORIN variants are associated with hypertension and heart disease. It remains unclear if and to what extent corin deficiency may contribute to heart failure (HF). Corin knockout (KO) mice were used as a model. Cardiac function was assessed by echocardiography and tissue analysis in Corin KO mice at different ages or subjected to transverse aortic constriction (TAC), which increased pressure overload. Heart and lung tissues were analyzed for cardiac hypertrophy and lung edema using wheat germ agglutinin, Sirius red, Masson's trichrome, and Prussian blue staining. Recombinant corin was tested for its effect on cardiac function in the TAC-operated Corin KO mice. Selected gene expression in the heart was examined by RT-PCR. ELISA was used to analyze factors in plasma. Corin KO mice had progressive cardiac dysfunction with cardiac hypertrophy and fibrosis after 9 months of age, likely due to chronic hypertension. When Corin KO mice were subjected to TAC at 10-12 weeks of age, cardiac function decreased more rapidly than in similarly treated wild-type mice. When the TAC-operated Corin KO mice were treated with recombinant corin protein, cardiac dysfunction, hypertrophy, and fibrosis were ameliorated. The corin treatment also decreased the gene expression associated with cardiac hypertrophy and fibrosis, increased plasma cGMP levels, lowered plasma levels of N-terminal pro-atrial natriuretic peptide, angiotensin II, and aldosterone, and lessened lung edema in the Corin KO mice subjected to TAC. Corin deficiency impairs cardiac function and exacerbates HF development in mice. Corin protein may be used to reduce cardiac hypertrophy and fibrosis, suppress the renin-angiotensin-aldosterone system, and improve cardiac function in HF.


Effects of a High-Protein/Low-Carbohydrate Diet versus a Standard Hypocaloric Diet on Weight and Cardiovascular Risk Factors: Role of a Genetic Variation in the rs9939609 FTO Gene Variant.
The common polymorphism rs9939609 of the fat mass- and obesity-associated gene (FTO) has been linked to obesity. Our aim was to investigate its role in weight loss after the administration of a high-protein/low-carbohydrate diet compared to a standard hypocaloric diet (1,000 kcal/day). During 9 months, 195 patients were randomly allocated to a high-protein hypocaloric diet (HP diet) and a standard hypocaloric diet (S diet). With the HP diet, BMI (-1.9 ± 1.2 vs. -2.10 ± 1.8; p < 0.05), weight (-6.5 ± 2.1 vs. -10.1 ± 4.1 kg; p < 0.05), fat mass (-3.9 ± 3.2 vs. -6.0 ± 3.4 kg; p < 0.05) and waist circumference (-5.7 ± 5.0 vs. -9.9 ± 5.5 cm; p < 0.05) decreased in both genotype groups (TT vs. AT + AA). With the S diet, BMI (-0.9 ± 1.1 vs. -1.8 ± 1.2; p < 0.05), weight (-3.2 ± 3.0 vs. -9.1 ± 3.6 kg; p < 0.05), fat mass (-3.0 ± 3.1 vs. -5.2 ± 3.1 kg; p < 0.05) and waist circumference (-3.1 ± 4.0 vs. -8.1 ± 4.9 cm; p < 0.05) decreased in both genotype groups. With the HP diet and in both genotype groups, glucose, insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, triglycerides and low-density lipoprotein (LDL) decreased. With the S diet, total cholesterol and LDL decreased. Weight loss was better in A allele carriers than noncarriers, and metabolic improvement was better with the HP diet.


The molecular behavior of apoA-I in human high density lipoproteins.
The properties of apoA-I in human high density lipoprotein (1.063 smaller than d smaller than 1.210 gm per ml) have been examined by fluorescence and difference absorption spectroscopy, while the behavior of the total complement of apoproteins has been evaluated by far ultraviolet circular dichroism. Marked increases in stability to temperature, pH, and guanidine hydrochloride were observed for apoA-I in the native particle as compared to the isolated state.


A validated chiral HPLC method for the determination of mebeverine HCl enantiomers in pharmaceutical dosage forms and spiked rat plasma.
A new, precise, simple and accurate HPLC method was developed for the first time to separate and determine mebeverine enantiomers. Enantiomeric resolution was achieved on a cellulose Tris (3,5-dimethylphenyl carbamate) column known as Chiralcel OD, with UV detection at 263 nm. The mobile phase consisted of n-hexane, isopropyl alcohol and triethylamine (90:9.9:0.1 v/v/v). Sample run time was 18 min. On using the chromatographic conditions described, mebeverine enantiomers were well resolved with mean retention times of about 11 and 14 min. A linear response (r>0.999) was observed over the concentration range 0.5-20 microg/mL racemic mebeverine. Precision, accuracy and stability were studied according to ICH guidelines. The limit of detection was found to be 0.05 microg/mL for each enantiomer of mebeverine. The proposed method was applied for analysis of mebeverine in commercially available tablets dosage formulations. Examples of application to biological samples are also given. Reanalysis of samples several weeks after the initial analysis showed no degradation of mebeverine.


Frequency of stent thrombosis after acute coronary syndromes (from the SYMPHONY and 2nd SYMPHONY trials).
We studied stent thrombosis in 4,607 patients with acute coronary syndromes who received a coronary stent as part of routine care during 2 trials of aspirin versus sibrafiban for secondary prevention. In these patients, stent thrombosis occurred more often than in previous patients who underwent elective percutaneous coronary intervention. These patients and their outcomes may be more representative of patients with typical acute coronary syndromes undergoing stenting in clinical practice.


Correction: A novel cell-free method to culture Schistosoma mansoni from cercariae to juvenile worm stages for in vitro drug testing.
[This corrects the article DOI: 10.1371/journal.pntd.0006590.].


Tumor BRCA Testing in High Grade Serous Carcinoma: Mutation Rates and Optimal Tissue Requirements.
Approximately 25% of women diagnosed with tubo-ovarian high-grade serous carcinoma have germline deleterious mutations in BRCA1 or BRCA2, characteristic of hereditary breast and ovarian cancer syndrome, while somatic mutations have been detected in 3-7%. We set out to determine the BRCA mutation rates and optimal tissue requirements for tumor BRCA testing in patients diagnosed with tubo-ovarian high-grade serous carcinoma. Sequencing was performed using a multiplexed polymerase chain reaction-based approach on 291 tissue samples, with a minimum sequencing depth of 500X and an allele frequency of >5%. There were 253 surgical samples (87%), 35 biopsies (12%) and 3 cytology cell blocks (1%). The initial failure rate was 9% (25/291), including 9 cases (3%) with insufficient tumor, and 16 (6%) with non-amplifiable DNA. Sequencing was successful in 78% (228/291) and deemed indeterminate due to failed exons or variants below the limit of detection in 13% (38/291). Repeat testing was successful in 67% (28/42) of retested samples, with an overall success rate of 86% (251/291). Clinically significant (pathogenic, likely pathogenic) variants were identified in 17% (48/276) of complete and indeterminate cases. Successful sequencing was dependent on sample type, tumor cellularity and size (p ≤ 0.001) but not on neoadjuvant chemotherapy or age of blocks (p > 0.05). Our study shows a 17% tumor BRCA mutation rate, with an overall success rate of 86%. Biopsy and cytology samples and post-chemotherapy specimens can be used for tumor BRCA testing, and optimal tumors measure ≥5 mm in size with at least 20% cellularity.


Organocatalytic Synthesis of Alkyne-Functional Aliphatic Polycarbonates via Ring-Opening Polymerization of an Eight-Membered-N-Cyclic Carbonate.
The synthesis of well-defined propargyl-functional aliphatic polycarbonates is achieved via the organocatalytic ring-opening polymerization of prop-2-yn-1-yl 2-oxo-1,3,6-dioxazocane-6-carboxylate (P-8NC) using a wide variety of commercially available or readily made, shelf-stable organocatalysts. The resulting homopolymers show low dispersities and end-group fidelity, with the versatility of the system being demonstrated by the synthesis of telechelic copolymers and block copolymers with molar mass up to 40 kDa.


A prospective population-based study of 598 cases of PPROM between 24 and 34 weeks' gestation: description, management, and mortality (DOMINOS cohort).
Description of mothers' characteristics, obstetricians' practices, and PPROM-linked mortality in all 81 maternity hospitals in the Rhône-Alpes Region, over a period of 2 years. Prospective cohort study of 598 women with PPROM between 24 and 34 weeks' gestation, leading to 680 births. At time of PPROM, collection of mothers' socio-economic characteristics, medical and obstetric histories and PPROM circumstances. Collection of perinatal management, neonates' medical status and postnatal referral. The birth rate after PPROM between 24 and 34 weeks' gestation was 0.47% (95% CI: 0.42-0.48). Sixty percent of PPROM occurred before 32 weeks' gestation and 98% of births before 37 weeks. The incidence of previous PPROM was 14.3%. Antibiotics, corticosteroids, and tocolytics were given to 82, 78, and 52% of women, respectively. The rate of antibiotics and antenatal corticosteroids varied with gestational age (lower rates for antibiotics just after the limit of viability (23-24 weeks) and after 32 weeks, higher rates of corticosteroids between 26 and 30 weeks). The PPROM-birth interval became shorter as gestation advanced. The incidence of C-section was 58.7% (n = 270), C-section before labour being the most frequent mode of delivery. Sixty-seven percent of neonates were born in Level-3 hospitals. The overall neonatal mortality rate at 28 days decreased with gestational age at PPROM, and was 17.2% (16/93), 3% (6/200), and 0.41% (1/241) at 24-27, 28-31 and 32-33 weeks of PPROM, respectively. After PPROM, antibiotics and antenatal corticosteroids were widely used in our cohort, and C-section rates were elevated. With that up-to-date management, the perinatal mortality rate was less than 3% following PPROM after 28 weeks' gestation.


Gait characteristics over the course of a race in recreational marathon competitors.
We analyzed gait and function of the supporting limb in participants of a marathon race at three stages: prerace, midrace (18 km), and near the end of the race (36 km). We confirmed that the most successful runners were able to maintain running speed for the duration of the race with little change in speed or gait. Speed slowed progressively during the race for those with slower race times, but stride frequency-stride length relationships remained normal for the speed they ran. These findings differ from most lab-based studies of fatigue, in which runners are forced to match a constant preset treadmill speed. Small changes in maximum ground force were seen in both slow- and fast-running participants as race end approached.


Cytogenetics of triplet conjugation in Tetrahymena: origin of haploid and triploid clones.
Triplet conjugation occurs frequently when three different mating types of T. thermophila are mixed under appropriate conditions. Genetic studies show that fertilization is usually tripolar, with each conjugant contributing a pronucleus to one mate and receiving a pronucleus from the other. Triplets are less common and less stable when only two mating types are mixed, and nuclear exchange is not always reciprocal. Some conjugants contribute a pronucleus but do not receive one in return. Others receive two pronuclei instead of one. Such triplets characteristically yield one haploid, one diploid and one triploid exconjugant, all of which are able to establish vigorous clones.


Investigation of a subunit protein vaccine for HFRS based on a consensus sequence between envelope glycoproteins of HTNV and SEOV.
Due to the global resurgence of hemorrhagic fever with renal syndrome (HFRS), more attention is being focused on this dangerous illness. In China and Korea, the only vaccines available are the virus-inactivated vaccine against Hantaan virus (HTNV) or Seoul virus (SEOV), but their efficacy and safety are inadequate. Therefore, it is important to develop new vaccines that are safer and more efficient to neutralize and regulate areas with a high prevalence of HFRS. We employed bioinformatics methods to design a recombinant protein vaccine based on conserved regions of protein consensus sequences in HTNV and SEOV membranes. The S2 Drosophila expression system was utilized to enhance protein expression, solubility and immunogenicity. After the Gn and Gc proteins of HTNV and SEOV were successfully expressed, mice were immunized, and the humoral immunity, cellular immunity, and in vivo protection of the HFRS universal subunit vaccine were systematically evaluated in mouse models. These results indicated that the HFRS subunit vaccine generated elevated levels of binding and neutralizing antibodies, particularly IgG1, compared to that of the traditional inactivated HFRS vaccine. Additionally, the spleen cells of immunized mice secreted IFN-r and IL-4 cytokines effectively. Moreover, the HTNV-Gc protein vaccine successfully protected suckling mice from HTNV infection and stimulated GC responses. In this research, a new scientific approach is investigated to develop a universal HFRS subunit protein vaccine that is capable of producing effective humoral and cellular immunity in mice. The results suggest that this vaccine could be a promising candidate for preventing HFRS in humans.


Two Brain Pathways Initiate Distinct Forward Walking Programs in Drosophila.
An animal at rest or engaged in stationary behaviors can instantaneously initiate goal-directed walking. How descending brain inputs trigger rapid transitions from a non-walking state to an appropriate walking state is unclear. Here, we identify two neuronal types, P9 and BPN, in the Drosophila brain that, upon activation, initiate and maintain two distinct coordinated walking patterns. P9 drives forward walking with ipsilateral turning, receives inputs from central courtship-promoting neurons and visual projection neurons, and is necessary for a male to pursue a female during courtship. In contrast, BPN drives straight, forward walking and is not required during courtship. BPN is instead recruited during and required for fast, straight, forward walking bouts. Thus, this study reveals separate brain pathways for object-directed walking and fast, straight, forward walking, providing insight into how the brain initiates context-appropriate walking programs.


Cochlear Implant Outcomes Following Vestibular Schwannoma Resection: Systematic Review.
Hearing loss remains a significant morbidity for patients with vestibular schwannomas (VS). A growing number of reports suggest audibility with cochlear implantation following VS resection; however, there is little consensus on preferred timing and cochlear implant (CI) performance. A systematic literature search of the Ovid Medline, Embase, Scopus, and clinicaltrails.gov databases was performed on 9/7/2018. PRISMA reporting guidelines were followed. Included studies reported CI outcomes in an ear that underwent a VS resection. Untreated VSs, radiated VSs, and CIs in the contralateral ear were excluded. Primary outcomes were daily CI use and attainment of open-set speech. Baseline tumor and patient characteristics were recorded. Subjects were divided into two groups: simultaneous CI placement with VS resection (Group 1) versus delayed CI placement after VS resection (Group 2). Twenty-nine articles with 93 patients met inclusion criteria. Most studies were poor quality due to their small, retrospective design. Group 1 had 46 patients, of whom 80.4% used their CI on a daily basis and 50.0% achieved open-set speech. Group 2 had 47 patients, of whom 87.2% used their CI on a daily basis and 59.6% achieved open-set speech. Group 2 had more NF2 patients and larger tumors. CI timing did not significantly impact outcomes. Audibility with CI after VS resection is feasible. Timing of CI placement (simultaneous versus delayed) did not significantly affect performance. Overall, 83.9% used their CI on a daily basis and 54.8% achieved open-set speech.


Improvement in sonochemical degradation of 4-chlorophenol by combined use of Fenton-like reagents.
Studies on the sonolysis of a wide range of organic compounds have demonstrated that ultrasonic irradiation has potential for decomposition of organic pollutants in hazardous wastewater. However, the ultrasonic irradiation alone cannot provide high enough rate of decomposition to be used practically. One of the solutions to increase the degradation efficiency is to combine the ultrasound application with other advanced chemical oxidation processes (AOPs). In this study, in order to increase the efficiency of ultrasonically assisted degradation of organic pollutants in water, we examined effects of three kinds of solid Fe-containing catalysts, namely iron powder, basic oxygen furnace (BOF) slag and mill scale on the degradation rate of 4-CP (4-chlorophenol) in aqueous solutions containing hydrogen peroxide. In the experiments, 4-CP was considered as a model organic compound. All three Fe-containing matters when react with hydrogen peroxide are involved in the Fenton-like reaction system, which is one of the promising AOPs. The results showed that both the iron powder and mill scale additions can accelerate the degradation of 4-CP, although the effect is dependent on the solution pH. All 4-CP could be decomposed for 2 min at pH=3 and for 1h at pH=5.6. On the other hand, the BOF slag had no catalysis effect on the 4-CP degradation because of higher concentration of calcium and lower concentration of iron.


Extracellular matrix couples the convergence movements of mesoderm and neural plate during the early stages of neurulation.
During the initial stages zebrafish neurulation, neural plate cells undergo highly coordinated movements before they assemble into a multicellular solid neural rod. We have previously identified that the underlying mesoderm is critical to ensure such coordination and generate correct neural tube organization. However, how intertissue coordination is achieved in vivo during zebrafish neural tube morphogenesis is unknown. In this work, we use quantitative live imaging to study the coordinated movements of neural ectoderm and mesoderm during dorsal tissue convergence. We show the extracellular matrix components laminin and fibronectin that lie between mesoderm and neural plate act to couple the movements of neural plate and mesoderm during early stages of neurulation and to maintain the close apposition of these two tissues. Our study highlights the importance of the extracellular matrix proteins laminin and libronectin in coupling the movements and spatial proximity of mesoderm and neuroectoderm during the morphogenetic movements of neurulation. Developmental Dynamics 245:580-589, 2016. © 2016 Wiley Periodicals, Inc.


The influence of intraperitoneally injected 6-hydroxydopamine on electroshock seizure in chicks and rats.
1. 6-Hydroxydopamine, injected intraperitoneally in rats and chicks, did not induce spontaneous seizures but produced significant alterations in the threshold to electroshock seizure in chicks; the particular effects were dose-dependent and time-dependent. 2. Administration of 6-hydroxydopamine to 3 day old chicks and rats in the first and third days after birth resulted in an increase in the proportion exhibiting tonic seizure with electroshock when tested after 10-12 weeks. 3. When 6-hydroxydopamine was injected intraperitoneally into adult rats and cocks, there was no significant alteration in seizure threshold. 4. The results suggest that 6-hydroxydopamine penetrates the central nervous system of young chicks and rats and that adrenergic mechanisms are probably involved in modulating seizure mechanisms in both the chick and rat.


Up-regulation of mitofusin-2 protects CD4+ T cells from HMGB1-mediated immune dysfunction partly through Ca(2+)-NFAT signaling pathway.
High mobility group box 1 protein (HMGB1) was recently discovered to be a critical late-acting cytokine and innate immune-modulating factor in sepsis, but the potential role and mechanism of HMGB1 in adaptive immunity remains elusive. The present study demonstrated that HMGB1 had a dual influence on immune function of CD4(+) T lymphocytes. Low dose of HMGB1 had no effect on the proliferation activity of CD4(+) T lymphocytes, but the Th1 cytokines production was increased. In contrast, treatment with high amount of HMGB1 suppressed the proliferative response and induced Th2 polarization of CD4(+) T lymphocytes. We found that the expression of mitofusin-2 (Mfn2; also named hyperplasia suppressor gene), a member of the mitofusin family, was decreased in CD4(+) T lymphocytes when stimulated with high dose of HMGB1. Up-regulation of Mfn2 attenuated the suppressive effect of HMGB1 on CD4(+) T lymphocytes, which was associated with profound elevation of intracellular calcium concentration ([Ca(2+)](i)) and nuclear factor of activated T cells (NFAT) activity. These results indicate that HMGB1 have a direct role on adaptive immunity, and the decrease of Mfn2 expression may be a major cause of HMGB1-mediated immune dysfunction and Ca(2+)-NFAT signaling defect of CD4(+) T lymphocytes.


Quantitative proteomic and transcriptional analyses reveal degradation pathway of γ-hexachlorocyclohexane and the metabolic context in the actinobacterium Streptomyces sp. M7.
Highly contaminated γ-hexachlorocyclohexane (lindane) areas were reported worldwide. Low aqueous solubility and high hydrophobicity make lindane particularly resistant to microbial degradation. Physiological and genetic Streptomyces features make this genus more appropriate for bioremediation compared with others. Complete degradation of lindane was only proposed in the genus Sphingobium although the metabolic context of the degradation was not considered. Streptomyces sp.M7 has demonstrated ability to remove lindane from culture media and soils. In this study, we used MS-based label-free quantitative proteomic, RT-qPCR and exhaustive bioinformatic analysis to understand lindane degradation and its metabolic context in Streptomyces sp. M7. We identified the proteins involved in the up-stream degradation pathway. In addition, results demonstrated that mineralization of lindane is feasible since proteins from an unusual down-stream degradation pathway were also identified. Degradative steps were supported by an active catabolism that supplied energy and reducing equivalents in the form of NADPH. To our knowledge, this is the first study in which degradation steps of an organochlorine compound and metabolic context are elucidate in a biotechnological genus as Streptomyces. These results serve as basement to study other degradative actinobacteria and to improve the degradation processes of Streptomyces sp. M7.


Effects of variability in manually contoured spinal cord masks on fMRI co-registration and interpretation.
Functional magnetic resonance imaging (fMRI) of the human spinal cord (SC) is a unique non-invasive method for characterizing neurovascular responses to stimuli. Group-analysis of SC fMRI data involves co-registration of subject-level data to standard space, which requires manual masking of the cord and may result in bias of group-level SC fMRI results. To test this, we examined variability in SC masks drawn in fMRI data from 21 healthy participants from a completed study mapping responses to sensory stimuli of the C7 dermatome. Masks were drawn on temporal mean functional image by eight raters with varying levels of neuroimaging experience, and the rater from the original study acted as a reference. Spatial agreement between rater and reference masks was measured using the Dice Similarity Coefficient, and the influence of rater and dataset was examined using ANOVA. Each rater's masks were used to register functional data to the PAM50 template. Gray matter-white matter signal contrast of registered functional data was used to evaluate the spatial normalization accuracy across raters. Subject- and group-level analyses of activation during left- and right-sided sensory stimuli were performed for each rater's co-registered data. Agreement with the reference SC mask was associated with both rater (F(7, 140) = 32.12, P < 2 × 10-16, η2 = 0.29) and dataset (F(20, 140) = 20.58, P < 2 × 10-16, η2 = 0.53). Dataset variations may reflect image quality metrics: the ratio between the signal intensity of spinal cord voxels and surrounding cerebrospinal fluid was correlated with DSC results (p < 0.001). As predicted, variability in the manually-drawn masks influenced spatial normalization, and GM:WM contrast in the registered data showed significant effects of rater and dataset (rater: F(8, 160) = 23.57, P < 2 × 10-16, η2 = 0.24; dataset: F(20, 160) = 22.00, P < 2 × 10-16, η2 = 0.56). Registration differences propagated into subject-level activation maps which showed rater-dependent agreement with the reference. Although group-level activation maps differed between raters, no systematic bias was identified. Increasing consistency in manual contouring of spinal cord fMRI data improved co-registration and inter-rater agreement in activation mapping, however our results suggest that improvements in image acquisition and post-processing are also critical to address.


Health-Economic Analyses of Diagnostics: Guidance on Design and Reporting.
Cost-effectiveness analyses (CEAs) can be used to assess the value of diagnostics in clinical practice. Due to the introduction of the European in vitro diagnostic and medical devices regulations, more clinical data on new diagnostics may become available, which may improve the interest and feasibility of performing CEAs. We present eight recommendations on the reporting and design of CEAs of diagnostics. The symptoms patients experience, the clinical setting, locations of test sampling and analysis, and diagnostic algorithms should be clearly reported. The used time horizon should reflect the time horizon used to model the treatment after the diagnostic pathway. Quality-adjusted life-years (QALYs) or disability-adjusted life-years (DALYs) should be used as the clinical outcomes but may be combined with other relevant outcomes, such as real options value. If the number of tests using the same equipment can vary, the economy of scale should be considered. An understandable graphical representation of the various diagnostic algorithms should be provided to understand the results, such as an efficiency frontier. Finally, the budget impact and affordability should be considered. These recommendations can be used in addition to other, more general, recommendations, such as the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) or the reference case for economic evaluation by the international decision support initiative.


Radiation Protection Capability of Operating Room Personnel: Development and Psychometric Properties of a Questionnaire.
Radiation protection is an important principle in some wards of the hospital such as radiology, catheterization laboratory and operating room. Due to the increasing use of radiation in the operating room, there is a need to design an accurate and appropriate tool to evaluate the radiation protection capability of operating room personnel. This study aims to test the psychometric properties of a questionnaire on radiation protection capability. This cross-sectional study was conducted in two stages. The first stage was designing items based on the review of available literature, and the second stage was measuring the validity and reliability of the questionnaire using face validity and content validity Content Validity Index (CVI) and Content Validity Ratio (CVR). Then the questionnaire was filled out by 200 operating room nurses to evaluate the construct validity by Principal Component Analysis method. Reliability of the questionnaire was evaluated by test-retest and Cronbach's alpha analysis method. Due to the results, test-retest correlation coefficient was 0.912, and Cronbach's alpha coefficient was 0.824, indicating a desirable internal consistency. This study introduces a valid and reliable questionnaire for evaluating the radiation protection capability of operating room nurses.


Metagenomics revealed a correlation of gut phageome with autism spectrum disorder.
The human gut bacteriome is believed to have pivotal influences on human health and disease while the particular roles associated with the gut phageome have not been fully characterized yet with few exceptions. It is argued that gut microbiota can have a potential role in autism spectrum disorders (ASD). The public microbiota database of ASD and typically developing (TD) Chinese individuals were analyzed for phage protein-coding units (pPCU) to find any link between the phageome and ASD. The gut phageome of ASD individuals showed a wider diversity and higher abundance compared to TD individuals. The ASD phageome was associated with a significant expansion of Caudoviricetes bacteriophages. Phages infecting Bacteroidaceae and prophages encoded within Faecalibacterium were more frequent in ASD than in TD individuals. The expansion and diversification of ASD phageome can influence the bacterial homeostasis by imposing pressure on the bacterial communities. In conclusion, the differences of phages community in in ASD and TD can be used as potential diagnosis biomarkers of ASD. Further investigations are needed to verify the role of gut phage communities in the pathogenesis of ASD.


Monitoring circulating platelet activity to predict cancer-associated thrombosis.
A characteristic clinical complication in cancer patients is the frequent incidence of thrombotic events. Numerous studies have shown hyperactive/activated platelets to be a critical earlier trigger for cancer-associated thrombus formation. However, there currently is no viable approach to monitor specific changes in tumor-associated platelet activity. Here, we describe a chromatograph-like microfluidic device that is highly sensitive to the activity status of peripheral circulating platelets in both tumor-bearing mice and clinical cancer patients. Our results show a strongly positive correlation between platelet activation status and tumor progression. Six-month follow-up data from advanced cancer patients reveal positive links between platelet activity level and thrombus occurrence rate, with a high predictive capacity of thrombotic events (AUC = 0.842). Our findings suggest that circulating platelet activity status determined by this microfluidic device exhibits sensitive, predictive potential for thrombotic events in cancer patients for directing well-timed antithrombosis treatment.


[Patellar giant cell tumour: presentation of a case and a review of the literature].
Patellar tumours are rare. They typically appear in young patients, and present with a non-specific pain in the knee. Giant cell tumour (GCT) are benign, but locally aggressive. Although they are usually found around the knee (40-60%), those affecting the patella have been classically described in the literature as uncommon. We describe the case of a 19 year old male complaining of pain in his knee, whose clinical examination suggested a meniscal tear. Plain radiological examination, as well as MRI, revealed a well circumscribed lytic lesion within the patella. The patient underwent arthroscopic surgery, during which an incisional biopsy was performed. Following pathology reports, which confirmed the suspected GCT, definitive surgery was performed. At 56 months after the surgery the patient remains asymptomatic and free of disease.


Tunable CO2 electroreduction to ethanol and ethylene with controllable interfacial wettability.
The mechanism of how interfacial wettability impacts the CO2 electroreduction pathways to ethylene and ethanol remains unclear. This paper describes the design and realization of controllable equilibrium of kinetic-controlled *CO and *H via modifying alkanethiols with different alkyl chain lengths to reveal its contribution to ethylene and ethanol pathways. Characterization and simulation reveal that the mass transport of CO2 and H2O is related with interfacial wettability, which may result in the variation of kinetic-controlled *CO and *H ratio, which affects ethylene and ethanol pathways. Through modulating the hydrophilic interface to superhydrophobic interface, the reaction limitation shifts from insufficient supply of kinetic-controlled *CO to that of *H. The ethanol to ethylene ratio can be continuously tailored in a wide range from 0.9 to 1.92, with remarkable Faradaic efficiencies toward ethanol and multi-carbon (C2+) products up to 53.7% and 86.1%, respectively. A C2+ Faradaic efficiency of 80.3% can be achieved with a high C2+ partial current density of 321 mA cm-2, which is among the highest selectivity at such current densities.


Measurement of the turnover of substrates of carbohydrate and protein metabolism using radioactive isotopes.
The rate of turnover of glucose or leucine can be measured in the steady state by using the radioactive isotopes 14C or 3H to 'trace' these metabolites. The tracer can either be injected or infused intravenously and its metabolism followed by monitoring levels of the tracer in blood, breath and urine. If a 14C labelled metabolite is used the oxidation rate may sometimes be determined by measuring the expiry rate of 14CO2. If the single injection technique is used the specific activity curve is fitted with an exponential function and the area under the curve calculated. Turnover rate is calculated from dose of isotope injected/area under the specific activity time curve. This technique can be used to construct a compartmental model to describe the behaviour of the metabolite. If the constant infusion technique is used, tracer is infused until a steady state level of tracer is achieved. This plateau is used to calculate the turnover of the metabolite from infusion rate of tracer/specific activity at steady state. While this latter method provides the simplest method of calculating turnover it cannot be used to model the data. The infusion technique can be used to measure changes in turnover and oxidation in the non-steady state. Tracer is infused to a steady state level and the system is then perturbed by for example, the infusion of a hormone. The changes in Ra and Rd can be determined either by using the Steele equation which assumes a single pool or by using compartmental analysis.


Assessment of the correlation of the tear breakup time with quality of vision and dry eye symptoms after SMILE surgery.
It is well reported that dry eye symptoms can increase after many refractive surgery procedures. This study aims to provide a clinical understanding of the correlation of fluorescein tear film breakup time (FTBUT) with quality of vision (QoV) and dry eye symptoms following small incision lenticule extraction surgery (SMILE). Patients electing to have SMILE surgery were subdivided into 2 groups: Group 1 included short preoperative FTBUTs of 3 to 6 seconds (s); Group 2 included long FTBUTs of ≥ 8 s. Uncorrected distance visual acuity, corrected distance visual acuity, manifest refraction, FTBUT, QoV and Ocular Surface Disease Index (OSDI) questionnaires were recorded 1 and 6 months postoperatively. Thirty-nine subjects were included in each group. There was no significant difference in visual outcomes between the 2 groups at both the 1- and 6-month postoperative assessments. FTBUT remained significantly lower in group 1. Oxford staining was initially higher for group 1 at 1 month (P = 0.007), but there was no significant difference at 6 months (P = 0.180). There was no significant difference in QoV or OSDI scores between the 2 groups at both postoperative visits. Low preoperative FTBUT (3-6 s) does not appear to negatively affect postoperative visual outcomes or results in a greater likelihood of dry eye symptoms and poor ocular surface compared to eyes with a longer preoperative FTBUT. These results suggest that a low preoperative FTBUT does not necessarily increase the likelihood of poor visual acuity, dry eyes symptoms, or poor ocular surface outcomes following SMILE surgery.


Hyponatremia and its associated factors in children admitted to the pediatric intensive care unit in eastern Ethiopia: a cross-sectional study.
Hyponatremia is a serious problem that leads to substantial increases morbidity and mortality in critically ill children. The identification of risk factors, implementation of preventive measures, and timely diagnosis and management are crucial to reduce adverse events related to hyponatremia. Despite the higher burden of the problem in Ethiopia, evidence related to the risk factors for hyponatremia among children in Ethiopia is limited; in particular, no study has been identified in eastern Ethiopia. Therefore, we aimed to determine the magnitude of hyponatremia and its associated factors in children admitted to the pediatric intensive care unit at the Hiwot Fana Comprehensive Specialized University Hospital. A facility-based cross-sectional study was conducted using 422 medical records of pediatric patients admitted to the pediatric intensive care unit at Hiwot Fana Comprehensive Specialized University Hospital from January 2019 to December 2022. Medical records were reviewed to collect data. Data were analyzed using a statistical package for social sciences (SPSS) version 26. A binary logistic regression model with an adjusted odds ratio (aOR) and a 95% confidence interval (CI) was used to identify factors associated with the outcome variable. Statistical significance was set at p < 0.05. The magnitude of hyponatremia was 39.1% (95% CL: 34.4-43.8%). The age of the child (aOR = 2.37;95% CL:1.31-4.31), diagnosis of sepsis (aOR = 2.33; 95% CL:1.41-3.84), surgical procedures (aOR = 2.39; 95% CL:1.26-4.56), nutritional status (aOR = 2.60; 95% CL:1.51-4.49), and length of hospital stay (aOR = 3.04; 95% CL: 1.73-5.33) were factors significantly associated with hyponatremia. Four out of ten children admitted to pediatric intensive care units had hyponatremia. Hyponatremia was significantly associated with the age of the child, malnutrition, sepsis, surgical procedures, and length of hospital stay. To reduce the burden of hyponatremia and associated mortality, attention should be focused on improving the care of malnourished children, and those with sepsis, and the quality of postoperative monitoring services. Moreover, intervention strategies aimed at reducing the burden of hyponatremia should target the identified factors.


Fracture of the navicular sesamoid bone: a case report.
The case history of a 45-year-old female patient who sustained a fracture of the right navicular sesamoid bone, probably due to sudden stretching of the tibialis posterior muscle, is described, and the literature briefly reviewed.