Impact of previous abdominal surgery on robotic-assisted rectal surgery in patients with locally advanced rectal adenocarcinoma: a propensity score matching study.
The application of minimally invasive surgery in patients with colorectal cancer (CRC) and a history of previous abdominal surgery (PAS) remains controversial. This retrospective study with propensity score matching (PSM) investigated the impact of PAS on robotic-assisted rectal surgery outcomes in patients with locally advanced rectal adenocarcinoma undergoing preoperative concurrent chemoradiotherapy (CCRT). In total, 203 patients with locally advanced rectal adenocarcinoma who underwent preoperative CCRT and robotic-assisted rectal surgery between May 2013 and December 2019 were enrolled. Patients were categorized into PAS and non-PAS groups based on the PAS history. The PSM caliper matching method with 1-to-3 matches was used to match PAS patients with non-PAS. Of the 203 enrolled patients, 35 were PAS patients and 168 were non-PAS patients. After PSM, 32 PAS patients and 96 non-PAS patients were included for analysis. No significant between-group differences were noted in the perioperative outcomes, including median console time (165 min (PAS) vs. 175 min (non-PAS), P = 0.4542) and median operation time (275 min (PAS) vs. 290 min (non-PAS), P = 0.5943) after PSM. Postoperative recovery and overall complication rates were also similar (all P > 0.05). Moreover, the between-group differences in pathological or short-term oncological outcomes were also nonsignificant (all P > 0.05). No 30-day postoperative deaths were observed in either group. The current results indicate that robotic-assisted surgery is safe and feasible for PAS patients with locally advanced rectal adenocarcinoma undergoing preoperative CCRT. However, future prospective randomized clinical trials are required to verify these findings.


Epigenomic analysis of Parkinson's disease neurons identifies Tet2 loss as neuroprotective.
Parkinson's disease (PD) pathogenesis may involve the epigenetic control of enhancers that modify neuronal functions. Here, we comprehensively examine DNA methylation at enhancers, genome-wide, in neurons of patients with PD and of control individuals. We find a widespread increase in cytosine modifications at enhancers in PD neurons, which is partly explained by elevated hydroxymethylation levels. In particular, patients with PD exhibit an epigenetic and transcriptional upregulation of TET2, a master-regulator of cytosine modification status. TET2 depletion in a neuronal cell model results in cytosine modification changes that are reciprocal to those observed in PD neurons. Moreover, Tet2 inactivation in mice fully prevents nigral dopaminergic neuronal loss induced by previous inflammation. Tet2 loss also attenuates transcriptional immune responses to an inflammatory trigger. Thus, widespread epigenetic dysregulation of enhancers in PD neurons may, in part, be mediated by increased TET2 expression. Decreased Tet2 activity is neuroprotective, in vivo, and may be a new therapeutic target for PD.


Recommendations on Measurement Units - Why and How.
Globally, laboratories are producing, communicating, and exchanging millions of laboratory examination values to multiple parties every day. For most values, 'measurement units' are required to make the numerical values comparable and meaningful. However, a non-systematic use of 'measurement units' can create errors in communication between health care providers and become a risk to patient safety. Therefore, the Committee of Nomenclature for Properties and Units (C-NPU) recommends using an unambiguous terminology of 'measurement units', for daily patient care and scientific publications. In this work, C-NPU summarizes the recommendations on 'measurement units', explaining the reasons and the principles of the 'measurement units' used in laboratory medicine.


Differences in the factors associated with tongue pressure between children with class I and Class II malocclusions.
The relationship between tongue pressure and masticatory performance during the mixed dentition period in cases of Class II malocclusion has not been clarified. The aim of this study was to determine differences in tongue pressure-related factors, including maxillofacial morphology and masticatory performance, between Class I and Class II malocclusions during the mixed dentition period. A total of 56 children with Class I malocclusion (12 boys, 16 girls) or Class II malocclusion (16 boys, 12 girls) with mixed dentition were included in the present study. Height, body weight, hand grip strength, maximum occlusal force, maximum tongue pressure, masticatory performance, and the number of decayed, missing, and filled teeth were measured in all participants. Their lateral cephalograms were also evaluated. The means of all measurements were compared between Class I and Class II malocclusions. Pearson's correlation coefficients were used to determine associations between maximum tongue pressure and other variables for each type of malocclusion. The maximum tongue pressure, hand grip strength, and maximum occlusal force in the Class II malocclusion group were significantly lower than those in the Class I malocclusion group (all, p < 0.05). The maximum tongue pressure was significantly positively correlated with hand grip strength, maximum occlusal force, masticatory performance, and SNB (sella, nasion, B point) angle in the Class I group (all, p < 0.05), and with height, body weight, and labial inclination of the central incisors in the Class II group (all, p < 0.05). The maxillofacial morphometric factors associated with tongue pressure were clearly different between cases of Class I and Class II malocclusion with mixed dentition. Masticatory performance and tongue pressure were significantly positively correlated in cases of Class I malocclusion, but not in cases of Class II malocclusion.


Twelve-year history of late-life depression and subsequent feelings to God.
Growing evidence shows several possible relations between religiousness and late-life depression. Emotional aspects of religiousness such as facets of the perceived relationship with God can be crucial in this connection. The aim of the current study was to examine the association between the course of late-life depression and feelings about God and religious coping. Longitudinal survey study; naturalistic; 12-year follow-up. Longitudinal Aging Study Amsterdam; population-based, in three regions in The Netherlands. A subsample of 343 respondents (mean age: 77.2 years), including all respondents with high levels of depressive symptoms at any measurement cycle between 1992 and 2003 (assessed by using the Center for Epidemiologic Studies Depression Scale and the Diagnostic Interview Schedule) and a random sample of nondepressed respondents who completed a postal questionnaire in 2005. Scales on God Image and Religious Coping. Twelve-year depression course trajectories serve as predicting variables and are specified according to recency and seriousness. Persistent and emergent depression are significantly associated with fear of God, feeling wronged by God, and negative religious coping. In terms of negative religious coping, significant associations were observed after adjustment for concurrent depression with a history of repeated minor depression and previous major depression. Late-life depression seems to maintain a pervasive relationship over time with affective aspects of religiousness. Religious feelings may parallel the symptoms of anhedonia or a dysphoric mood and could represent the experience of an existential void.


Computer-assisted live cell analysis of mitochondrial membrane potential, morphology and calcium handling.
Mitochondria are crucial for many aspects of cellular homeostasis and a sufficiently negative membrane potential (Deltapsi) across the mitochondrial inner membrane (MIM) is required to sustain most mitochondrial functions including ATP generation, MIM fusion, and calcium uptake and release. Here, we present a microscopy approach for automated quantification of Deltapsi and mitochondrial position, shape and calcium handling in individual living cells. In the base protocol, cells are stained with tetramethyl rhodamine methyl ester (TMRM), a fluorescent cation that accumulates in the mitochondrial matrix according to Deltapsi, and visualized using video-microscopy. Next, the acquired images are processed to generate a mitochondria-specific binary image (mask) allowing simultaneous quantification of mitochondrial TMRM fluorescence intensity, shape and position. In a more advanced version of this protocol a mitochondria-targeted variant of green fluorescent protein (mitoAcGFP1) is expressed to allow mask making in TMRM-stained cells. The latter approach allows quantification of Deltapsi in cells with a substantially depolarized Deltapsi. For automated quantification of mitochondrial calcium handling in space and time mitoAcGFP1-expressing cells are stained with rhod-2, a fluorescent calcium indicator that accumulates in the mitochondrial matrix. In this paper, a detailed step-by-step description of the above approaches and its pitfalls is provided.


Rapid development of fatal TB constrictive pericarditis after cardiac surgery.
We report the case of a 75-year-old male of Asian origin who developed TB constrictive pericarditis less than 6 weeks after CABG. He had no history of active TB, but did show a strong Heaf test reaction in 1987, following a period of weight loss. This was thought to be indicative of previous infection and was not actively treated. Cases of postcardiac surgery constrictive pericarditis have been reported in the literature, but to our knowledge, there is no report of development of TB constrictive pericarditis in such a short period following surgery.


Protective effects of caffeic acid phenethyl ester (CAPE) and thymoquinone against cigarette smoke in experimental bone fracture healing.
This study investigated the protective characteristics of caffeic acid phenethyl ester (CAPE) and thymoquinone (TMQ) against the effects of cigarette smoke in recovery from bone fractures. Sixty Wistar albino rats were divided into six groups (n = 10). The rats' femur bones were fractured and then fixed with microplates and microscrews. In the CAPE group, CAPE was given by intraperitoneal injection for 30 days at a dose of 10 μmol/kg once a day. In the TMQ group, TMQ was given orogastrically for 30 days at a dose of 10 mg/kg once a day. In the cigarette groups, CAPE was given by intraperitoneal injection for 30 days at a dose of 10 μmol/kg once a day (CAPE-CG), TMQ was given orogastrically for 30 days at a dose of 10 mg/kg once a day (TMQ-CG), and controls were exposed to cigarette smoke three times a day for 8 min each time for 30 days. The controls received no postoperative treatment. The rats were sacrificed on the 30th day following surgery. According to the histopathological and immunohistochemical results, cigarette smoke had a negative impact on bone healing. TMQ and CAPE increased bone formation and reduced bone destruction. Therefore, TMQ and CAPE were found to be partially protective against the adverse effects of smoking on bone tissue.


Protective and Therapeutic Role of Ginkgo Biloba Extract Through TRPV1 Channels in an in Vitro Alzheimer's Disease Model.
The effect of Ginkgo biloba (GB) on mitochondria-dependent TRPV1 ion channels in neuroblastoma cells was investigated by creating an Alzheimer's disease (AD) model. Okadaic acid was applied on SH-SY5Y cells to create an AD model. After cellular differentiation, the study was organized with the seven main groups, examining the effect of GB on calcium depended TRPV1 channels in neuroblastoma cells AD, has been established in vitro. The higher Ca2+ concentration was detected in the GB+AD, AD and AD+GB groups when compared with the control (p<0.001). The Ca2+ level was lower in GB+AD and AD+GB groups than in the AD group (p<0.001). Also, cytosolic Ca2+ concentration was lower in the GB+AD than in the AD+GB group (p<0.05), the apoptosis and intracellular reactive oxygen species (ROS) values were higher in the GB+AD, AD and AD+GB groups than in the control (p<0.001). The apoptosis and intracellular ROS values were higher in AD group than in the GB+AD and AD+GB group (p<0.001) and the apoptosis level was higher in AD+GB group than GB+AD group (p<0.001) and the mitochondrial depolarization, caspase 3 and caspase 9 levels were higher in the GB+AD, AD and AD+GB groups when compared to the control group (p<0.001). Also, the values were lower in the GB+AD group, AD group and AD+GB groups when compared with the GB+AD+capsazepine group, AD+capsazepine group and AD+GB+capsazepine respectively (p<0.001). These results show us that GB has a protective effect besides its therapeutic effect in Alzheimer's disease via TRPV1 channel.


Galanin: presence and distribution in the brain and pituitary of Rhinella arenarum (Amphibia: Anura) during development.
The immunohistochemical distribution of galanin (Gal) in the brain and pituitary of Rhinella arenarum was studied during development. Gal-immunoreactivity was first observed in the brain just after hatching in anterior preoptic area, infundibular area, median eminence and pars distalis of the pituitary as well as in the olfactory epithelium. At the beginning of prometamorphosis new Gal-immunoreactive (ir) cells were observed in the olfactory nerve and bulb. Later in prometamorphosis new Gal-ir cells were observed in the telencephalon, suprachiasmatic nucleus, rostral rhombencephalon and in the pars nervosa of the pituitary. The most numerous accumulations of Gal-ir neurons throughout the larval development were observed in the ventral hyphothalamus where numerous Gal-ir cells of cerebrospinal fluid-contacting type were found. During metamorphic climax and soon after we did not detect Gal-ir neurons in the pallium, medial or pretectal dorsal thalamus. In the median eminence and pars distalis of the pituitary many Gal-ir fibers were found during development indicating that Gal may play a role in the modulation of hypophyseal secretion. Furthermore, the distribution of Gal-ir elements observed throughout larvae development indicates that galaninergic system maturation continues until sexual maturity.


Focused ultrasound ablation of renal and prostate cancer: current technology and future directions.
Focused ultrasound technology provides a noninvasive modality for tissue ablation. Although widely used for the treatment of benign prostatic hyperplasia, its application for the treatment of localized prostate cancer is controversial, and its use for the treatment of small renal masses remains experimental. This article outlines the underlying principles of thermal focused ultrasound technology and its limitations as evident in the current literature. The principles and technique of nonthermal cavitational ultrasound tissue ablation is described with a summary of preliminary experimental data.


SR-AttNet: An Interpretable Stretch-Relax Attention based Deep Neural Network for Polyp Segmentation in Colonoscopy Images.
Colorectal polyp is a common structural gastrointestinal (GI) anomaly, which can in certain cases turn malignant. Colonoscopic image inspection is, thereby, an important step for isolating the polyps as well as removing them if necessary. However, the process is around 30-60 min long and inspecting each image for polyps can prove to be a tedious task. Hence, an automatic computerized process for efficient and accurate polyp isolation can be a useful tool. In this study, a deep learning network is introduced for colorectal polyp segmentation. The network is based on an encoder-decoder architecture, however, having both un-dilated and dilated filtering in order to extract both near and far local information as well as perceive image depth. Four-fold skip-connections exist between each spatial encoder-decoder due to both type of filtering and a 'Feature-to-Mask' pipeline processes the decoded dilated and un-dilated features for final prediction. The proposed network implements a 'Stretch-Relax' based attention system, SR-Attention, to generate high variance spatial features in order to obtain useful attention masks for cognitive feature selection. From this 'Stretch-Relax' attention based operation, the network is termed as 'SR-AttNet'. Training and optimization is performed on four different datasets, and inference has been done on five (Kvasir-SEG, CVC-ClinicDB, CVC-Colon, ETIS-Larib, EndoCV2020); all of which output higher Dice-score compared to state-of-the-art and existing networks. The efficacy and interpretability of SR-Attention is also demonstrated based on quantitative variance. In consequence, the proposed SR-AttNet can be considered for an automated and general approach for polyp segmentation during colonoscopy.


Determination of cell tropism of HIV-1.
With the discovery that changes in the biological properties of HIV-1 correlate with the progression to disease, it became more and more important to develop assays to distinguish between the viral phenotypes. In this chapter, it is described how the biological phenotype of HIV-1 with regard to cellular tropism can be determined on primary monocyte-derived macrophages, established T-cell lines: MT2, SupT1, and H9, and promonocytic cell lines: U937, HL-60, and THP-1.


Complete response to nivolumab in Kirsten rat sarcoma virus oncogene KRAS-G12C mutant metastatic lung adenocarcinoma: a case report.
The advent of immunotherapies has ushered in a new era in the treatment of non-small cell lung carcinoma. Although immunotherapies are associated with improved clinical outcomes, studies report a median overall survival of 11 months with progression-free survival of 2.5 months with the use of nivolumab for pretreated metastatic non-small cell lung cancer. Herein, we describe a case of advanced non-small cell lung carcinoma that has shown exceptional response to immunotherapy, with the patient being in complete response for the past 6 years since commencement of nivolumab. We report the case of a 58-year-old female Caucasian, an ex-smoker with 40-pack-year history of smoking, who presented with cough and chest pain and was subsequently diagnosed with metastatic pulmonary adenocarcinoma. The tumor was positive for Kirsten rat sarcoma virus oncogene KRAS-G12C mutation and had high programmed death-1 ligand expression. She was commenced on first-line chemotherapy with carboplatin and gemcitabine with disease response, then continued on maintenance pemetrexed. She was then commenced on immunotherapy with nivolumab, with complete response for a total of 6 years. She does not report any adverse events. Currently, she shows no evidence of recurrence of non-small cell lung carcinoma. The exceptional response to immunotherapy seen in this case may be explained by the presence of Kirsten rat sarcoma virus oncogene mutation, which is associated with enhanced clinical response to programmed death-1 ligand inhibitors. This report emphasizes the urgent need for further studies evaluating the role of Kirsten rat sarcoma virus oncogene mutation in determining the clinical efficacy of immunotherapies. This would enable us to make effective evidence-based clinical interventions in the treatment of non-small cell lung carcinoma.


[Isolated pleural metastases from an atypical meningioma].
Less than 2 per 1,000 meningiomas are complicated by extra-cranial metastases. These are most often found in the lung parenchyma, liver or lymph nodes. They almost always occur in anaplastic meningiomas (grade III according to OMS) and much more rarely in atypical meningiomas (grade II). We report a case of pleural metastases from a primary frontal atypical meningioma with no other extra-cranial spread. Poorly differentiated meningioma presents many morphological and immuno-histochemical similarities to malignant mesothelioma. For this reason the diagnosis of pleural metastase from a meningioma cannot be made without knowledge of the primary meningeal tumour and its histological type.


Influence of age and of pre-treatment with D-cycloserine on the behavior of ethanol-treated rats tested in the elevated plus-maze apparatus.
There is evidence that ethanol is able to influence central functions through the antagonism of the NMDA-receptor system. It has been shown that this system is also involved in the modulation of anxiety-related behavior in rats. Recently, we observed gender- and age-related behavioral influences in rats tested on the elevated plus-maze apparatus The present study was undertaken in order to investigate: (1) the effects of ethanol (0.8, 1.0 or 1.2 g/kg, i.p.) on the behavior of male and female rats tested on the elevated plus-maze at 2, 3, 4 or 5 months of age; (2) the effect of the pre-treatment with D-cycloserine (3.0 or 6.0 mg/kg), an agonist of the glutamate NMDA-receptor system, 30 min before the ethanol (1.2 g/kg) injections, in rats tested in the elevated plus-maze at 2 months or 4 months of age. The results demonstrated that ethanol did not affect the time spent and the frequency of entries on the open arms of the elevated plus-maze in rats tested at 2 months of age, but increased these parameters in older animals. Moreover, the results showed that D-cycloserine, at doses that did not affect the behavior of control animals, antagonized the increased frequency of entries and time spent on open arms produced by ethanol in rats tested at 4 months of age. Our results suggest an age-related influence on the anxiolytic action of ethanol in rats tested in the elevated plus-maze. Moreover, the results suggest that the NMDA-receptor system can be involved in this effect, and strengthens the evidence for the participation of the NMDA-receptor system in anxiety-related behavior.


Current status of benign biliary disorders in Japan and accuracy rates of preoperative diagnoses. Collective review of 14,654 patients.
Data on 14,654 patients preoperatively diagnosed for benign lesions who had undergone surgical treatment during a 2 year period (April 1979 to March 1981) were obtained from 145 institutions. A total of 18,891 biliary disorders were confirmed and classified into 18 groups: stones in the gallbladder, 12,272 patients (83.7 percent of all patients); stones in the extrahepatic bile duct, 3,605 patients (24.6 percent); stones in the intrahepatic bile duct, 570 patients (3.9 percent); acalculous cholecystitis, 463 patients (3.2 percent); idiopathic dilatation of bile ducts, 375 patients (2.6 percent); stenosing papillitis, 274 patients (1.9 percent); benign stricture of bile ducts, 133 patients (0.9 percent); and others. Malignant tumors were found in 243 patients, of whom 132 (54.3 percent) were not expected to have gallbladder cancer. Accuracy rates for preoperative diagnoses in the patients with gallstones of the intrahepatic or extrahepatic bile ducts or the gallbladder, idiopathic dilatation of the bile ducts, benign stricture of the bile ducts, or benign stenosis of the papilla of Vater were higher than 90 percent. However, the false-negative rates for these six disorders, except gallstones of the gallbladder, were higher than 16 percent. Therefore, despite advances in diagnostic procedures before surgery, intraoperative examinations remain indispensable for determining the most effective approach to surgical repair.


Scarring of the C8-T1 roots with partial avulsion in situ in total obstetric brachial plexus palsy.
Primary exploration of the brachial plexus in infants with obstetric palsy may reveal scarring of the lower roots with evidence of partial avulsion-in-situ. As we have been treating this lesion by neurolysis only, we aimed to investigate the recovery of hand function following such approach. A series of 14 cases of total obstetric palsy with with evidence of partial avulsion-in-situ of the lower roots were included. All lesions were treated by neurolysis only (with no neurotization of the lower roots). Management of the injured upper roots was done by neurotization. Recovery was assessed as per our motor grading system. After a minimum follow-up of 4 years, hand functional recovery was considered good in 7 patients and excellent in the remaining 7 patients. We highlight the scarring of lower roots with evidence of partial avulsion-in situ in obstetric palsy. We also document that neurolysis is an acceptable approach to such lesions. Level of Evidence: Level IV, therapeutic study.


Cleavage of double-strand DNA by linear and triangular trinuclear copper complexes.
Two trinuclear copper(II) complexes with linear or triangular metal-binding pendants, [Cu(3)(L(1))](6+) (1) and [Cu(3)(L(2))](6+) (2), have been synthesized and characterized, where L(1)=N,N,N',N'-tetra[(2-pyridyl)methyl]-5,5'-bis(aminomethyl)-2,2'-dipyridyl, L(2)=N,N,N',N',N'',N''-hexa[(2-pyridyl)methyl]-1,3,5-tris(aminomethyl)-benzene. Interactions of them with calf thymus DNA have been investigated by measuring the changes in the melting temperature. The obtained DeltaT(m) values indicated that both 1 and 2 exhibited very high affinities towards DNA and strong destabilization of DNA, and were far better than their mononuclear analogues. In the absence of any reducing agent, 1 showed markedly higher nuclease activity than 2, and its hydrolytic process was further clarified in the presence of a few of radical scavengers. The pseudo Michaelis-Menten kinetic parameters (k(cat)) were determined through DNA cleavage versus the concentration of the complexes, to be 6.05 and 0.19 h(-1) for 1 and 2 respectively. Much higher nuclease activity of 1 is probably attributed to its linear multiple metal sites that fit well to the phosphodiester backbone of nucleic acid. DNA cleavage versus the concentration of DNA shows that rate constants rapidly increase at beginning and then markedly decrease with increasing DNA concentration. It is likely that excess substrates would promote intermolecular interaction between a complex and more plasmid DNA(s) and weaken its intramolecular cooperative effect that is propitious to DNA cleavage.


The impact of pH on cytotoxic effects of three root canal irrigants.
Cytotoxicity of root canal irrigants is important due to their close contact with host tissues. This study was to assess the possible impact of pH on cytotoxic effects of MTAD, 17% EDTA, and 2.6% NaOCl on the human gingival fibroblasts using MTT assay. Human gingival fibroblasts were exposed to the irrigants and their viability was assessed after 1, 6, and 12 h. The pH of the medium was measured in each interval. Light absorption values were measured for each culture medium using Elisa Reader device. NaOCl had significantly less cytotoxicity than EDTA and MTAD. Also irrigants cytotoxicity decreased in 12, 1, and 6 h, respectively. It seems that variation of the pH resulted in variation in the cytotoxicity of solutions; i.e., it follows the pattern of the pH variation.


Brainstem carbachol injections in the urethane anesthetized rat produce hippocampal theta rhythm and cortical desynchronization: a comparison of pedunculopontine tegmental versus nucleus pontis oralis injections.
Previous research has demonstrated that brainstem injections of acetylcholine agonists (e.g., carbachol) produced electrophysiological indicators of rapid-eye-movement (REM) sleep in the cat. Recent reports now indicate that this phenomenon may hold true for rats as well. Relatively few reports, however, have examined the effect of these injections on REM indicators in the anesthetized rat, a preparation useful for elucidating underlying neurobiological mechanisms controlling REM sleep processes. The present study compared the effect of injections of carbachol (5 micrograms in 250 nl) into the pedunculopontine tegmental nucleus (PPTg) or the nucleus pontis oralis (NPO) on two tonic indicators of REM sleep in the urethane-anesthetized rat. Namely, changes in the hippocampal EEG and in the cortical EEG. Carbachol injections into either site produced a change in both the hippocampal EEG and cortical EEG to a REM-like state at short latencies. The length of these changes (duration of effect), however, was site-dependent. Thus, PPTg carbachol injections induced significantly longer lasting effects in both the hippocampal and cortical EEG than did NPO injections. The results that brainstem carbachol injections in rats, as in cats, may provide a useful model for investigating tonic REM sleep processes.


Personalized medicine begins with the phenotype: identifying antipsychotic response phenotypes in a first-episode psychosis cohort.
Here, we present a clustering strategy to identify phenotypes of antipsychotic (AP) response by using longitudinal data from patients presenting first-episode psychosis (FEP). One hundred and ninety FEP with complete data were selected from the PEPs project. The efficacy was assessed using total PANSS, and adverse effects using total UKU, during one-year follow-up. We used the Klm3D method to cluster longitudinal data. We identified four clusters: cluster A, drug not toxic and beneficial; cluster B, drug beneficial but toxic; cluster C, drug neither toxic nor beneficial; and cluster D, drug toxic and not beneficial. These groups significantly differ in baseline demographics, clinical, and neuropsychological characteristics (PAS, total PANSS, DUP, insight, pIQ, age of onset, cocaine use and family history of mental illness). The results presented here allow the identification of phenotypes of AP response that differ in well-known simple and classic clinical variables opening the door to clinical prediction and application of personalized medicine.


Effects of task-oriented treadmill-walking training on walking ability of stoke patients.
Generally, treadmill-walking training focuses on weight bearing and the speed of walking. However, changes in direction, speed, and slope while walking require adaptation. The effects of task-oriented treadmill-walking training (TOTWT) on the walking ability of stroke patients were evaluated. Subjects were randomly divided into two groups: the task-oriented treadmill-walking training (TOTWT) group and the conventional treadmill-walking training (CTWT) group. Evaluation was performed before the commencement of the training and again 4 and 8 wk after training was initiated. The OptoGait system measured gait parameters. The Timed Up and Go test and 6-min walk test were also performed. Within each group, both the TOTWT and the CTWT groups significantly differed before and after the intervention in all tests (P < 0.05); the CTWT group showed greater improvement in all tests following TOTWT (P < 0.05). TOTWT improves gait and rehabilitation in the stroke-affected limb, and also improves general gait characteristics.


Environmental planning and management in an age of uncertainty: the case of the Water Framework Directive.
Scenario planning is one of the most prominent methods applied by organisations to assist long-term decision making. This paper uses a case study method to demonstrate how scenarios can be operationalised to inform future strategies and to challenge rigid silo-based decision making approaches. The WaterProof Northwest scenarios developed by the authors in collaboration with a range of stakeholders, and described within this paper, offer a platform for considering the future of the water environment. The scenarios were developed in the context of meeting the goals of the European Water Framework Directive. This Directive has the core aim of improving the chemical and ecological status of Europe's water bodies. The scenarios highlight that water bodies in the case study area (the region of Northwest England) are impacted directly by a wide array of driving forces which will affect the state of the water environment over the coming decades. This analysis demonstrates that organisations responsible for creating and implementing long-term plans and policies to manage water are often far removed from the forces that will influence the effectiveness of the exercises that they are engaged in. The WaterProof Northwest scenarios highlight that organisations need different decision making approaches in order to adapt to modern environmental challenges. They also raise questions over whether environmental legislation such as the Water Framework Directive should incorporate a futures perspective in recognition of the wide ranging forces influencing their implementation.


Celecoxib reduces hyperalgesia and tactile allodynia in diabetic rats.
In the present study we determined the antihyperalgesic and antiallodynic effect of celecoxib in diabetic rats as well as the possible participation of opioid receptors in the mechanism of action of celecoxib in these rats. Experimental diabetes was induced by streptozotocin. Formalin (0.5%) was used to produce hyperalgesia in non-diabetic and diabetic rats. von Frey filaments were used to determine the 50% withdrawal threshold in diabetic rats. Oral administration of celecoxib (0.3-30 mg/kg) reduced formalin-induced nociceptive behavior during phase 2. Systemic pre-treatment (-10 min) with naltrexone (3mg/kg) prevented celecoxib-induced antihyperalgesia in formalin-treated diabetic rats. Furthermore, naltrexone as well as the δ and κ opioid receptor antagonists naltrindole (3mg/kg) and 5'-guanidino naltrindole (1mg/kg), respectively, fully prevented celecoxib-induced antihyperalgesia (10mg/kg) in formalin-treated non-diabetic and diabetic rats. Furthermore, celecoxib (0.3-30 mg/kg) produced an antiallodynic effect in diabetic rats. Pre-treatment with naltrexone (3mg/kg) fully prevented the antiallodynic effect of celecoxib at 0.3, 3 and 10mg/kg. In contrast, this dose of naltrexone only partially prevented the antiallodynic effect of celecoxib 30 mg/kg. Naltrexone and naltrindole (3mg/kg), but not 5'-guanidino naltrindole (1mg/kg), fully prevented the antiallodynic effect of celecoxib in diabetic rats. Data suggest that celecoxib produces an antihyperalgesic and antiallodynic effect in diabetic rats. These effects seem to result from activation of μ, δ and κ opioid receptors for antinociception and μ and δ for antiallodynia. Celecoxib could be useful to treat neuropathic pain in diabetic patients.


Comparison of outcomes of open and laparoscopic appendectomy: A retrospective cohort study.
Open appendectomy has been the conventional choice of treatment for acute appendicitis. However, nowadays laparoscopic approach is emerging for the benefits it provides, like lesser postoperative pain and lesser duration of hospital stay, but at the cost of higher expenses and longer operative duration. A retrospective cohort study was done at Shree Birendra Hospital from January 2018 to December 2021, with a total study population of 450 participants (300 in open appendectomy and 150 in laparoscopic appendectomy). Preoperative. Intraoperative and postoperative parameters were compared and analyzed between two groups using SPSS-25. The mean age was 26.72 ± 9.70 in the open appendectomy (OA) and years 23.89 ± 6.32 in the laparoscopic appendectomy (LA) group. (p = 0.010) There was a significant difference between the mean operative time (46.08 ± 13.10 min in OA and 56.86 ± 11.70 min in LA, p = 0.000), length of hospital stay (1.28 ± 0.80 days in OA and 1.07 ± 0.25 days in LA, p = 0.000), course of oral analgesics (3.55 ± 0.68 days in OA and 3.00 days in LA p = 0.000) between OA groups and LA groups, while the total number of complications was less in the LA group however there was no statistically significant difference postoperative complications (p = 0.124) between the two groups in the surgical findings. All in all, the laparoscopic approach is a better option for uncomplicated appendicitis due to its less postoperative pain and shorter duration of hospital stay.


Accelerating the integration of China into the global development of innovative anticancer drugs.
The aim of this Policy Review was to compare China's overall and synchronous participation in clinical trials for innovative anticancer drugs with that of the USA, the EU, Japan, and South Korea, and to assess changes in the participation rate trends in these five regions. Relevant data from the top 20 international pharmaceutical companies from 2011 to 2021 were systematically collected from the Trialtrove and Pharmaprojects databases. Among the 8260 trials for 954 new anticancer drugs identified, China was involved in 8·8% of the trials and with 20·4% of the drugs being trialled. These participation rates are significantly lower than those for South Korea (14·5% of trials and 36·3% of drugs), Japan (16·1% of trials and 38·7% of drugs), the EU (40·6% of trials and 67·7% of drugs), and the USA (65·7% of trials and 91·2% of drugs; p<0·0001 for all). Similar results were found for the synchronous participation rate, defined as the proportion of drugs or trials at the highest development stage internationally, for the 803 tested drugs, which ranged from 9·0% in China to 87·7% in the USA. China's participation rate in early phase trials (4·4%) and in synchronous trials (5·4%) was even lower, in stark contrast to that of the USA (66·1% for early phase trials and 89·1% for synchronous trials). The fastest growing annual rate of participation in trials was observed in China (15·7%), followed by South Korea (8·2%) and Japan (6·8%); no change was detected in the USA or the EU. This Policy Review shows that Chinese participation in the clinical development of innovative cancer drugs by international pharmaceutical companies has increased over the past decade, but an obvious gap persists in comparison with the USA, the EU, Japan, and South Korea, especially in its synchronous participation and early participation rates.


The nadA gene of Pseudomonas fluorescens PGPR strain 267.1.
An insertion mutant of Pseudomonas fluorescens PGPR strain 267.1 was found to be auxotrophic for niacin (nicotinic acid) and could not synthesize quinolinic acid. The Tn5 interrupted gene was cloned and sequenced. The cloned fragment contained an open reading frame, nadA, capable of encoding a 359-amino-acid protein (39.0 kDa) with substantial identity to various bacterial quinolinate synthetases. The nadA gene complemented quinolinic acid synthesis deficiency and niacin auxotrophy of the P. fluorescens 106 P nadA mutant.


The effect of therapeutic touch on sleep quality and fatigue in menopausal women.
The management of well-known and common complaints such as insomnia and fatigue experienced in the menopausal period has the potential to affect many aspects of life in women during this period positively. This research was carried out to determine the effect of therapeutic touch on sleep quality and fatigue in menopausal women. This randomized controlled experimental study was conducted with 48 (24 in the intervention group and 24 in the control group) women who sought treatment in the gynecological outpatient clinic of a public hospital. According to the study procedure, while the intervention group received therapeutic touch, the control group received SHAM therapeutic touch for 10 min a day for five consecutive days. Data were collected through the Personal Information Form, the Pittsburgh Sleep Quality Index, and the Piper Fatigue Scale. The median post-test total sleep quality score was significantly lower in the intervention group than in the control group (p=0.010). However, the mean total fatigue scores did not differ significantly between the groups (p=0.917). The results of this study showed that therapeutic touch was effective in improving sleep quality, but it did not affect fatigue in menopausal women.


A pilot study of video-motion analysis in endovascular surgery: development of real-time discriminatory skill metrics.
Accurate assessment and credentialing of physicians is essential. Objective motion analysis of guide-wire/catheter manipulation to assess proficiency during endovascular interventions remains unexplored. This study aims to assess its feasibility and its role in evaluation of technical ability. A semi-automated catheter-tracking software was developed which allows for frame-by-frame motion analysis of fluoroscopic videos and calculation 2D catheter tip path-length. 21 interventionalists (6 cardiologists, 8 interventional radiologists, 7 vascular surgeons; 14/21 had performed >500 endovascular procedures) performed an identical carotid artery stenting procedure (CAS) on a VIST simulator (Mentice, Gothenburg, Sweden). Operators were sub-divided into four categories according to CAS experience: 6 inexperienced (0 CAS-group A), 3 low-volume (1-20 CAS-group B), 5 moderate-volume (21-50 CAS-group C) and 7 high-volume (>50 CAS-group D) CAS experience. Total PL was calculated for each case and comparisons made between groups. PL was correlated with: quantitative, simulator-derived metrics and qualitative performance scores (generic and procedure-specific) derived from post-hoc video analysis by three blinded observers. Group D used 5160.3 (inter-quartile range- IQR 4046.4-7142.9) pixels of movement, compared to 6856.7 (5914.4-8106.9) for group A (p = 0.046); 10,905.1 (7851.1-14,381.5) for group B (p = 0.017); and 9482.6 (8663.5-13,847.6) for group C (p = 0.003). Statistically significant inverse correlations were seen between total PL and qualitative performance scores (rho = -0.519 for generic (p = 0.027) rho = -0.567 for procedure-specific (p = 0.014) scores). PL did not correlate with any of the simulator-derived metrics (errors, contrast volume, total procedure and fluoroscopy times, cine-loops used). Endovascular instrument video motion analysis is feasible and may represent a valuable tool for the objective assessment of endovascular skill.


An association between the rs1799853 and rs1057910 polymorphisms of CYP2C9, the rs4244285 polymorphism of CYP2C19 and the prevalence rates of drug-resistant epilepsy in children.
Epilepsy is a neurologically based disease. Literature data indicate a certain association between the polymorphism of these genes, which participate in the metabolism of drugs (CYP), and drug-resistant epilepsy. The reports describe studies in which an association was evaluated between the rs1799853 (430C > T) and rs1057910 (1075A > C) polymorphisms of CYP2C9 gene and the rs4244285 (c.681G > A) polymorphism of CYP2C19 gene on one hand and the incidence of drug-resistant epilepsy in children on the other. The above-mentioned polymorphisms were assessed by the PCR-RFLP technique in a group of patients with drug-resistant (n = 106) and drug-responsive (n = 80) epilepsy, as well as in non-epileptic children (n = 97), all of them hospitalised at the Department of Neurology of the Institute-Polish Mother's Memorial Hospital in Lodz. It was demonstrated that CT genotype of the rs1799853 polymorphism of CYP2C9 gene and GA genotype of the rs4244285 polymorphism of CYP2C19 gene caused an enhanced risk of epilepsy. It was also shown that the occurrence of C-G-A haplotype, when referred to the rs1799853 polymorphism of CYP2C9 gene and the rs4244285 polymorphism of CYP2C19 gene, could be associated with a decreased risk of epilepsy occurrence. In case of the rs1799853 polymorphism in CYP2C9 gene, the occurrence of T allele four times increases the risk of drug-resistance in patients with diagnosed epilepsy. The obtained results indicated that the rs1799853 and rs1057910 polymorphisms of CYP2C9 gene and the rs4244285 polymorphism of CYP2C19 gene could be associated with the occurrence of drug-resistant epilepsy in children.


Management of Gastroesophageal Junction Tumors.
Gastroesophageal junction tumors have been increasing in incidence over time, with most tumors presenting at a locally advanced stage. The treatment plan depends on the stage at diagnosis. PET-CT and endoscopic ultrasound are used to determine clinical stage. Depending on the location of the tumor in the esophagus and stomach, treatment can include chemotherapy with or without radiation, followed by surgery if there is no disease progression. Prognosis is related to stage at diagnosis and response to preoperative treatment. Most surgery for gastroesophageal junction tumors can be performed minimally invasively, which helps decrease postoperative length of stay and morbidity from surgery.


CT perfusion imaging for childhood moyamoya disease before and after surgical revascularization.
Moyamoya disease is a progressive occlusive disease of the circle of Willis with prominent collateral arterial formation. We report on a 12-year-old girl with moyamoya disease presenting with transient ischemic attacks (TIAs). Surgical indirect revascularization was performed. The patient did not suffer further TIAs at 12 month follow-up. Pre and postoperative cerebral perfusion were studied in quantitative single photon emission computerized tomography (SPECT) and CT perfusion imaging. CT perfusion imaging demonstrated postoperatively increased cerebral blood flow as well as SPECT before and after revascularization. Furthermore, the area of decreased vascular reserve in SPECT with acetazolamide corresponded to areas of increased cerebral blood volume in CT perfusion imaging. CT perfusion imaging was equivalent to SPECT in accuracy, and superior in spatial resolution. CT perfusion imaging is likely to become more widely available as an easy-to-perform technique for assessing cerebral perfusion in a patients with moyamoya disease.


Facile fabrication of ternary MWCNTs/ZnO/Chitosan nanocomposite for enhanced photocatalytic degradation of methylene blue and antibacterial activity.
Developing a cheap, stable and effective photocatalyst is necessary for remediation of persistent organic pollutants. To address this challenge, we proposed a unique interfacial engineering technique and proper bandgap matching strategy to synthesize MWCNTs/ZnO/Chitosan ternary nanocomposite for effective photocatalytic application. The features of the prepared samples were determined by FESEM, TEM, EDX, elemental mapping, AFM, FT-IR, XRD, UV-Vis spectroscopy and BET surface analysis. The obtained results showed successful fabrication of synthesized nanocomposites with enhanced surface area. Degradation effect of nanostructures on methylene blue (MB) and antibacterial activity against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Bacillus subtilis (B. subtilis) pathogenic strains were investigated. The proposed photocatalytic mechanism illustrated the electron transfer facilitated by MWCNTs/ZnO/Chitosan structure which results in spatial separation of electron-hole pairs. Compared with ZnO and ZnO/Chitosan, the prepared MWCNTs/ZnO/Chitosan ternary nanocomposite showed high usage of UV illumination and superior separation of photogenerated electron-hole pairs. MWCNTs/ZnO/Chitosan illustrated 86.26% adsorption rate and outstanding increased photocatalytic activity on MB degradation efficiency of 98.76% after 20 min. Stability of photocatalyst reached from 98.76% initial decolorization to 85% at the fourth cycle. In addition, the ternary nanocomposite also exhibited remarkable bactericidal activity against gram-positive (S. aureus) and (B. subtilis) and gram-negative (E. coli) bacteria strains. Due to the obtained results, the prepared nanocomposite would be an efficient candidate photocatalyst with antibacterial properties.


PD-L1+ lung cancer stem cells modify the metastatic lymph-node immunomicroenvironment in nsclc patients.
Cancer stem cells (CSCs) are implicated in tumor initiation and development of metastasis. However, whether CSCs also affect the immune system is not fully understood. We investigated correlations between the PD-L1+ CSCs, changes in T-cell phenotype in metastatic and non-metastatic lymph nodes (LNs) and response to treatment. LNs' aspirates were obtained during the EBUS/TBNA procedure of 20 NSCLC patients at different stages of the disease. CSCs and T-cell characteristics were determined by flow cytometry. PD-L1+ CSCs positively correlated with the percentage of Tregs, PD-1+ CD4 T cells and Tim3+ CD4+ T cells, whereas PD-L1+ CSCs were negatively correlated with CD4+ T cells and CD28+ CD4+ T cells. The percentage of PD-L1+ CSCs was higher in patients with progressive disease (PD) as compared to patients with stable disease (SD) or partial response (PR). Among T cells, only PD-1+ CD4+ T cells and Tim3+ CD4+ T-cell frequencies were higher in patients with PD as compared to patients with SD or PR. The frequency of PD-L1+ CSCs associates with an altered T-cell frequency and phenotype indicating that CSCs can affect the immune system. The higher percentage of PD-L1+ CSCs in patients with PD may confirm their resistance to conventional therapy, suggesting that CSCs may be an interesting target for immunotherapy.


Identification and characterization of Noc2 as a potential Rab3B effector protein in epithelial cells.
The Rab3 family small G proteins (Rab3A-D) are involved in the regulated secretory pathway of brain and secretory tissues. Among Rab3-interacting proteins, Rabphilin-3, Rim, and Noc2, all of which contain a conserved Rab3-binding domain (RBD3), are generally recognized Rab3 effector proteins in neurons and secretory cells. Although Rab3B was also detected in epithelial cells, its function remained unknown. We isolated cDNA sequences from human epithelial Caco2-cell mRNA by degenerate RT-PCR based on the conserved amino acid sequence of RBD3. Multiple cDNA clones were identified as encoding Noc2. Northern blot analysis revealed that Noc2 mRNA was expressed not only in secretory tissues but also in epithelial tissues and cell lines. A pull-down assay demonstrated that Noc2 bound to Rab3B in a GTP-dependent manner. When Noc2 was co-expressed with the GTP-bound form of Rab3B, it was recruited from the cytosol to perinuclear membranes. Furthermore, overexpression of Noc2 inhibited the cell-surface transport of basolateral vesicular stomatitis virus glycoprotein. These results suggest that Noc2 functions as a potential Rab3B effector protein in epithelial cells.


Prevalence of aflatoxin, ochratoxin and deoxynivalenol in cereal grains in northern Uganda: Implication for food safety and health.
Mycotoxin contamination of cereals is a significant health risk for humans and animals, particularly in developing countries. To gain insight into food safety related to agricultural practices, we assessed levels of mycotoxin contamination in 105 samples of food grains raised and stored for consumption by rural households in the post-conflict districts of Kitgum and Lamwo in Northern Uganda. Aflatoxin, ochratoxin and deoxynivalenol (DON) contamination was assessed by quantitative enzyme-linked immunosorbent assay. Total aflatoxin in the foods analyzed varied from nd (not detected) to 68.2 μg/Kg. Ochratoxin ranged from 0.1 to 16.4 μg/Kg. DON ranged from nd to 2606 μg/Kg. The mean concentration of total aflatoxins was significantly higher (P = 0.002) in sorghum than in millet, maize and sesame seeds. Frequency of co-occurrence of two mycotoxins ranged from 8.3 to 100%, with the highest being aflatoxin and ochratoxin in sorghum. Co-occurrence of all three mycotoxins ranged from 8.3 to 35.3%, with the highest again being in sorghum. Mean levels of aflatoxins concentration in sorghum samples were 11.8 μg/Kg, exceeding the Ugandan national regulatory limits of 10 μg/Kg. Furthermore, 46.5% of the sorghum consumed in both districts exceeded this limit, and 86.1% of sorghum samples exceeded the European Union (E.U.) maximum tolerable limit of 4 μg/Kg. The Estimated Daily Intake (EDI) and Hazard Indices (HI) values were in the range of 1.2 × 10-5-91.521 and 1.3 × 10-7 to 0.0059, respectively. In conclusion, our results provide evidence of high levels of mycotoxin contamination and co-occurrence in food grains in Northern Uganda with aflatoxins and ochratoxins at high levels in all the cereal types analyzed. Consumption of cereals cultivated in this region poses no health risk of mycotoxins exposure since HI values obtained were less than 1.


Positron annihilation localization by nanoscale magnetization.
In positron emission tomography (PET), the finite range over which positrons travel before annihilating with an electron places a fundamental physical limit on the spatial resolution of PET images. After annihilation, the photon pair detected by the PET instrumentation is emitted from a location that is different from the positron-emitting source, resulting in image blurring. Here, we report on the localization of positron range, and hence annihilation quanta, by strong nanoscale magnetization of superparamagnetic iron oxide nanoparticles (SPIONs) in PET-MRI. We found that positron annihilations localize within a region of interest by up to 60% more when SPIONs are present (with [Fe] = 3 mM) compared to when they are not. The resulting full width at half maximum of the PET scans showed the spatial resolution improved by up to [Formula: see text] 30%. We also found evidence suggesting that the radiolabeled SPIONs produced up to a six-fold increase in ortho-positronium. These results may also have implications for emerging cancer theranostic strategies, where charged particles are used as therapeutic as well as diagnostic agents and improved dose localization within a tumor is a determinant of better treatment outcomes.


Intramuscular hemorrhages in the pathway of an electric current through the body - two case reports.
Intramuscular hemorrhages at autopsy can have a variety of traumatic as well as non-traumatic causes, but their recognition in electrical deaths is almost a rarity. We report on two autopsy cases of electrical fatalities, the first relating to a portion of the right upper human extremity, consisting (only) of the forearm and hand, while the other case relates to a female child who died after a high voltage electrical shock. In both cases, layered dissection of the upper limb revealed fresh intramuscular hemorrhages in the skeletal muscles that could be topographically related to the path taken by the current through the body. Externally visible electric marks were present in both cases. The hemorrhages were most likely caused by current-induced tetanic muscle contractions, producing an internal muscle trauma with rupture of fibers and bleedings. In complex situations, such as inconspicuous marks or a complete lack of visible signs on the body, the finding may be helpful in solving the case in consideration of the case history and circumstances. The vitality, topography, and pattern of the hemorrhages are discussed in the light of the available literature.


Incidence of and Reasons and Determinants Associated with Retransitioning from Biosimilar Etanercept to Originator Etanercept.
Patients in clinical practice are transitioned from originator etanercept (OR-ETA) to biosimilar etanercept (BS-ETA), but some subsequently retransition. Insights into the incidence of and reasons for retransitioning and the characteristics of these patients could help clinicians successfully introduce biosimilars. Our objective was to assess the incidence of and reasons for retransitioning from BS-ETA to OR-ETA in patients with a rheumatic disease (RD) and to explore the determinants thereof. This cohort study included all patients with RD who had transitioned from OR-ETA to BS-ETA in a large hospital in the Netherlands in 2016. The incidence of retransitioning to OR-ETA and the 1-year persistence with BS-ETA were assessed using the Kaplan-Meier estimator. Reasons for retransitioning were classified as related to (1) efficacy, (2) adverse events, (3) the administration device, and (4) other. Determinants for retransitioning, including baseline and treatment characteristics, were assessed in a nested case-control study using conditional logistic regression. We included 342 patients (median age 57.8 years; 53.5% females). At 1 year after transitioning, 9.4% of patients had retransitioned to OR-ETA and 69.7% were persistent with BS-ETA. At the end of follow-up (median 4.4 years), 47 patients (13.7%) had retransitioned to OR-ETA. The median time until retransitioning was 0.55 years (interquartile range 0.2-1.3). Most patients (n = 34 [72.3%]) retransitioned because of a (perceived) loss of effect, followed by adverse events (23.4%). In total 3.8% of patients switched to another biological treatment or a Janus kinase inhibitor; 17.1% of patients discontinued BS-ETA without retransitioning or switching within the first year. Univariate determinants for retransitioning included initiating corticosteroids or intensifying immunomodulator treatment (odds ratio [OR] 2.37; 95% confidence interval [CI] 1.03-5.45) and the number of visits to the rheumatology department (OR 2.06; 95% CI 1.55-2.74). In the multivariate analysis, only the number of visits to the rheumatology department remained significantly associated with retransitioning (OR 2.19; 95% CI 1.60-3.01). When introducing a biosimilar in clinical care, clinicians should anticipate that one in seven patients will retransition to the originator. A (perceived) loss of effect was the most frequently reported reason for retransitioning. Patients who visited the rheumatology department more frequently had an increased risk of retransitioning, which is likely to be related to patients reporting a loss of effect and to adverse events resulting in more visits to the rheumatology department.


Regulation of Morphology and Electronic Structure of NiSe2 by Fe for High Effective Oxygen Evolution Reaction.
With the development of hydrogen-energy economy, it is urgent for researchers to explore high effective non-noble metal electrocatalysts for oxygen evolution reaction (OER). Nickel-based selenides have good conductivity and easy to regulate, which make them to be a promising OER electrocatalysts. Hence, many researchers engineering the structure of Nickel-based selenides to further improve the OER performance. In this paper, NixFe1-x Se2 porous-nano-microspheres with different ratio were synthesized. Results confirm that Fe not only affects the number of active sites in NiSe2 , but also affects the intrinsic activity by forming lattice defects. Besides, introduction of Fe can change the redox ability of Ni cation and Se anion, thus, reducing the average valence state of Ni cation in NiOOH. As a result, the current density of OER is improved remarkably. When the current density reaches 10 mA cm-2 , the overpotential is only 285 mV.


High-dose-rate intraluminal brachytherapy during preoperative chemoradiation for locally advanced rectal cancers.
To determine the feasibility and safety of high dose rate intraluminal brachytherapy (HDR-ILBT) boost during preoperative chemoradiation for rectal cancer. Between 2008 and 2009, thirty-six patients with locally advanced rectal cancer (≥ T3 or N+), were treated initially with concurrent capecitabine (825 mg/m(2) oral twice daily) and pelvic external beam radiotherapy (EBRT) (45 Gy in 25 fractions), then were randomized to group A; HDR-ILBT group (n = 17) to receive 5.5-7 Gy × 2 to gross tumor volume (GTV) and group B; EBRT group (n = 19) to receive 5.4 Gy × 3 fractions to GTV with EBRT. All patients underwent total mesorectal excision. Grade 3 acute toxicities were registered in 12 patients (70.6%) in group A and in 8 (42.1%) in group B. Complete pathologic response of T stage (ypT0) in group A was registered in 10 patients (58.8%) and in group B, 3 patients (15.8%) had ypT0 (P < 0.0001). Sphincter preservation was reported in 6/9 patients (66.7%) in group A and in 5/10 patients (50%) in group B (P < 0.01). Overall radiological response was 68.15% and 66.04% in Group A and B, respectively. During a median follow up of 18 mo, late grade 1 and 2 sequelae were registered in 3 patients (17.6%) and 4 patients (21.1%) in the groups A and B, respectively. HDR-ILBT was found to be effective dose escalation technique in preoperative chemoradiation for rectal cancers, with higher response rates, downstaging and with manageable acute toxicities.


Clinical inertia in the management of Type 2 diabetes metabolic risk factors.
Delays in the initiation and intensification of medical therapy may be one reason patients with diabetes do not reach evidence-based goals for metabolic control. We assessed intensification of medical therapy over time, comparing the management of hyperglycaemia, hypertension, and hyperlipidaemia. Prospective cohort study of 598 adults with Type 2 diabetes receiving primary care in an academic medical centre from May 1997 to April 1999. We assessed whether patients failing to achieve standard treatment goals for haemoglobin A1c (HbA1c), systolic blood pressure (SBP), or low density lipoprotein (LDL) cholesterol when last measured during 12 months (Year 1, 5/97-4/98) had increases in their corresponding medical regimen during the following 12 months (Year 2, 5/98-4/99). Among untreated patients in Year 1, seven of 12 (58%) of those above goal for HbA1c were initiated on medical therapy in Year 2, compared with 16 of 48 (34%) above SBP goal (P=0.02) and 26 of 115 (23%) above LDL cholesterol goal (P=0.02). Among patients on therapy and above goal, 124 of 244 (51%) patients with elevated HbA1c had their regimen increased in Year 2, compared with 85 of 282 (30%) with elevated SBP (P<0.001) and 22 of 79 (30%) with elevated LDL cholesterol (P<0.001). From Year 1 to Year 2 there was a decline in the overall proportion of patients above goal for LDL cholesterol (from 58% to 45%, P=0.002) but not for HbA1c or blood pressure. Greater initiation and intensification of pharmaceutical therapy, particularly for elevated blood pressure or cholesterol, may represent a specific opportunity to improve metabolic control in Type 2 diabetes.


Mechanical properties and antibacterial activities of novel starch-based composite films incorporated with salicylic acid.
To control food contamination and meet the growing demand for high quality food, a novel and excellent starch composite film as packing material with optimized physical, mechanical properties and antimicrobial activity was produced in this paper. Starch-based composite films incorporated with salicylic acid (SA) and waxy maize starch nanoparticles/κ-carrageenan (WMSNs/KC) were used to achieve antimicrobial activity and improve the mechanical properties. WMSNs were fabricated through enzymolysis and recrystallisation method, followed by individually adding KC to form WMSNs/KC by self-assembly, and used as a nanofiller and stabilizer to be incorporated into hydroxypropyl tapioca starch-based films at a concentration of 0-9%. Characterization of macromorphology and scanning electron microscope indicated the starch composite films with WMSNs/KC were smooth, uniform, and transparent. X-ray diffraction pattern and Thermogravimetric analysis also showed strong interactions such as hydrogen bond formation among films, WMSNs/KC and SA. Compared with the pure starch-based films, the composite films reinforced by the addition of WMSNs/KC significantly increased the tensile strength, water vapor barrier and thermal stability, while the transparency and elongation at break decreased slightly. Moreover, the starch composite films showed excellent antimicrobial activity for three typical undesired microorganisms in foods, Escherichia coli, Staphylococcus aureus, and Bacillus subtilis.


Exposure characteristics and risk assessment of air particles in a Chinese hotel kitchen.
The hazards of kitchen particles have attracted social attention, but their distribution characteristics and risk assessment are rarely reported. To explore the temporal and spatial distribution characteristics of kitchen particles, analyze the variations in characteristics of number concentration (NC), mass concentration (MC), surface area concentration (SAC), and particle size distribution, provide reference indexes for evaluating worker exposure, evaluate the risk of kitchen particles, as well as suggest improvements and control measures. Different cooking posts in a Chinese hotel kitchen were selected to monitor exposure to particles, explore the temporal and spatial distribution characteristics of NC, MC, and SAC of particles in the cooking post, analyze changes in the particle size, compare the individual exposure of particles between the cooking and steaming posts, and analyze the correlation between NC, MC, and SAC. Risk assessment of kitchen ultrafine particles was performed using a Nanotool. The sizes and fluctuation ranges of NC10 - 500nm at cooking posts during lunch preparation and at peak periods were significantly higher than those at the end of the lunch period. The mean values of MC10 - 500nm during the lunch preparation peak and ending periods were 0.149, 0.229, and 0.151 mg m-3, respectively. The mean values of SAC10 - 500nm were 225, 961, and 466 μm2·cm-3, respectively. The mode diameter of exposed particles at the cooking post [(34.98 ± 2.33) nm] was higher than that at the steaming post [(30.11 ± 2.17) nm] (P < 0.01). The correlation between SAC10 - 500nm and NC10 - 500nm (r = 0.703) was the strongest. Nanotool gave a hazard rating ratio, exposure rating ratio, and risk ratio of 0.75. The sizes of the NC, MC, and SAC of the particles at the cooking post were related to the kitchen operations. Since kitchen particles are of high exposure and risk levels, protective measures should be formulated and implemented to deal with them safely.


Air pollutants are negatively associated with vitamin D-synthesizing UVB radiation intensity on the ground.
Atmospheric levels of pollutants may reduce the UVB intensity at the earth's surface, with a subsequent reduction in cutaneous vitamin D synthesis. We investigated the association of various pollutants with UVB intensity on the ground. Four-year data obtained from four weather stations from across Kuwait were analyzed by median regression. Pollutants that were negatively associated with UVB were [β (95% CI)]: benzene [- 2.61 (- 4.13, - 1.09)], ethyl-benzene [- 2.20 (- 3.15, - 1.25)], ozone [- 0.23 (- 0.28, - 0.17)], nitric oxide [- 0.11 (- 0.15, - 0.06)], sulfur dioxide [- 0.10 (- 0.17, - 0.04)] and particulate matter PM10 [- 0.002 (- 0.003, - 0.002)]. Pollutants that were negatively associated with the UVB/UVA ratio were [β (95% CI)]: benzene [- 15.57 (- 24.94, - 6.20)], nitric oxide [- 0.53 (- 0.81, - 0.25)], ozone [- 0.38 (- 0.70, - 0.06)], and total hydrocarbon [- 0.02 (- 0.04, - 0.01)]. Furthermore, benzene and nitric oxide levels were higher in the morning and evening hours, which are the times of most solar exposure in this region due to high temperature during midday. In addition to other known factors, attenuation of UVB by these pollutants may contribute to lower vitamin D levels in populations. In addition to direct public health hazard, these pollutants may contribute to the very high prevalence of VDD in this region.


[Human herpesvirus-8 in Hungarian blood donors and in patients with Kaposi sarcoma].
The pathogenic role of Kaposi's sarcoma associated herpesvirus or human herpesvirus-8 in the development of Kaposi's sarcoma is widely accepted today. Here the authors report an indirect immunofluorescence assay based seroepidemiologic study. Their results indicate that 1.56% (17/1089) of the Hungarian adult population and 100% (12/12) of Kaposi's sarcoma patients have serum antibodies to HHV-8 latent nuclear antigens.


MERS-CoV in Camels but Not Camel Handlers, Sudan, 2015 and 2017.
We tested samples collected from camels, camel workers, and other animals in Sudan and Qatar in 2015 and 2017 for evidence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. MERS-CoV antibodies were abundant in Sudan camels, but we found no evidence of MERS-CoV infection in camel workers, other livestock, or bats.


AmyJ33, a truncated amylase with improved catalytic properties.
Biochemical and kinetic properties are of special interest for the specific applications of α-amylases in industrial sectors such as textile industries, detergents, biofuels and food among others. Therefore, protein engineering is currently directed towards a continuous demand to improve the properties of amylases and thus meet the specific characteristics for various industrial sectors. In the present work, modular protein engineering was performed to improve the biochemical and kinetic properties of AmyJ33r an α-amylase isolated from Bacillus siamensis JJC33M consisting of five domains, A, B, C, D and E (SBD) (Montor-Antonio et al. in 3 Biotech 7:336, 2017. https://doi.org/10.1007/s13205-017-0954-8 ). AmyJ33r is not active on native starch, only showing activity on gelatinized starch. At the C-terminal, AmyJ33r has a starch binding domain (SBD, domain E) belonging to the CBM26 family. In this study, four truncated versions were constructed and expressed in E. coli (AmyJ33-AB, AmyJ33-ABC, AmyJ33-ABCD, and SBD) to determine the role of the A, B, C, D, and E domains in the biochemical behavior of AmyJ33r on starch. Biochemical and kinetic characterization of the truncated versions showed that domain C is essential for catalysis; domain D improved enzyme activity at alkaline pH values, is also involved negatively in thermostability at 40, 50, and 60 °C and its presence favored the production of maltooligosaccharides with a higher degree of polymerization (DP4). E domain have interaction with raw starch, also the deletion of E domain (SBD) favors the affinity for the substrate while the deletion of D domain increased enzyme kcat at the time of product release. In conclusion, AmyJ33-ABC has better kinetic parameters than AmyJ33-ABCD and AmyJ33r, but is less stable than these two enzymes.


Sleep in disorders of consciousness: behavioral and polysomnographic recording.
Sleep-wakefulness cycles are an essential diagnostic criterion for disorders of consciousness (DOC), differentiating prolonged DOC from coma. Specific sleep features, like the presence of sleep spindles, are an important marker for the prognosis of recovery from DOC. Based on increasing evidence for a link between sleep and neuronal plasticity, understanding sleep in DOC might facilitate the development of novel methods for rehabilitation. Yet, well-controlled studies of sleep in DOC are lacking. Here, we aimed to quantify, on a reliable evaluation basis, the distribution of behavioral and neurophysiological sleep patterns in DOC over a 24-h period while controlling for environmental factors (by recruiting a group of conscious tetraplegic patients who resided in the same hospital). We evaluated the distribution of sleep and wakefulness by means of polysomnography (EEG, EOG, EMG) and video recordings in 32 DOC patients (16 unresponsive wakefulness syndrome [UWS], 16 minimally conscious state [MCS]), and 10 clinical control patients with severe tetraplegia. Three independent raters scored the patients' polysomnographic recordings. All but one patient (UWS) showed behavioral and electrophysiological signs of sleep. Control and MCS patients spent significantly more time in sleep during the night than during daytime, a pattern that was not evident in UWS. DOC patients (particularly UWS) exhibited less REM sleep than control patients. Forty-four percent of UWS patients and 12% of MCS patients did not have any REM sleep, while all control patients (100%) showed signs of all sleep stages and sleep spindles. Furthermore, no sleep spindles were found in 62% of UWS patients and 21% of MCS patients. In the remaining DOC patients who had spindles, their number and amplitude were significantly lower than in controls. The distribution of sleep signs in DOC over 24 h differs significantly from the normal sleep-wakefulness pattern. These abnormalities of sleep in DOC are independent of external factors such as severe immobility and hospital environment.


The effect of alcoholism on salsolinol and biogenic amines in human brain.
Chronic alcoholics with a well documented history of alcohol abuse were divided at autopsy into two groups, intoxicated alcoholics (IA, with blood ethanol levels) and sober alcoholics (SA, without blood ethanol levels). Norepinephrine (NE), 4-hydroxy-3-methoxyphenyl-glycol (HMPG), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), salsolinol (SAL) and methylated salsolinol (M-SAL) in caudate nucleus and putamen from the two groups of alcoholics and an age-matched control group were analysed with gas chromatography-mass spectrometry. HMPG was significantly increased in the brains of the alcoholics compared to controls (IA, P less than 0.001 and SA, P less than 0.05) indicating an increased NE turnover in the brains of alcoholics. 5-HIAA, the major 5-hydroxytryptophan (5-HT) metabolite, was increased in the caudate nucleus from SA (P less than 0.05) compared to controls and IA. This could be interpreted as an increased turnover of 5-HT at abstinence. SAL can be formed from DA and acetaldehyde and/or pyruvate. SAL was found in all brains studied. The levels were about 1% of the dopamine concentrations. SAL had a tendency to be increased in brains of IA compared to control brains. The most remarkable finding was that SAL was significantly decreased in both the caudate nucleus and putamen from SA compared to controls and IA. M-SAL showed tendencies in the same directions as SAL. DA did not show any significant changes, but tended to be lower in SA.(ABSTRACT TRUNCATED AT 250 WORDS)


Dense fine speckled immunofluorescence pattern in a Chinese population: Prevalence and clinical association.
To provide information on the prevalence and possible clinical association in a Chinese population for medical practice of the dense fine speckled pattern (DFS pattern). A retrospective study was conducted with patients who had the DFS pattern from June 2018 to December 2019 in West China Hospital. A total of 469 patients (1.27% of patients with positive anti-nuclear antibody indirect immunofluorescence (ANA IIF) test results) revealed the DFS pattern, of which 92.96% had isolated DFS pattern and 23.67% had titers above/equal to 1:320. The average age of patients with the DFS pattern was 43.45 years, and females accounted for 76.97% of them. Ten different kinds of diseases made up the vast majority of the disease spectrum, in which inflammatory or infectious diseases (46.11%), mental diseases (21.45%), and systemic autoimmune rheumatic diseases (SARDs) (18.23%) ranked in the top three. The most common SARDs were rheumatoid arthritis (RA), undifferentiated connective tissue disease (UCTD), and systemic lupus erythematosus (SLE). Forty-six patients (10.55%) had positive or suspicious extractable nuclear antigen (ENA) antibodies test results and a higher risk of suffering from SARDs. Forty-seven patients would be missed if the DFS pattern with negative ENA antibodies test result was considered as exclusion criterion of SARDs. The DFS pattern is basically isolated and with low titer. It is unwise to exclude the diagnosis of SARDs only depending on the appearance of the DFS pattern. Autoimmune diseases-related antibodies, clinical information of patients, and long-term follow-up are of great importance to avoid missed or delayed diagnosis of SARDs.


Women's preferences for misoprostol in case of early pregnancy failure.
The aim of this study was to assess the preference of women with early pregnancy failure for treatment with misoprostol as compared to curettage. Women with early pregnancy failure were interviewed and asked whether they were motivated to trade a non-invasive but potentially less effective treatment with misoprostol at the virtually 100% guarantee of complete evacuation after curettage. All women had a structured interview, in which they were informed about both treatment options. The women were asked for a treatment preference in case the complete evacuation rate after misoprostol was set at 100%. In case the women preferred misoprostol, the complete evacuation rate was subsequently decreased to 10% using steps of 5%. The study group consisted of 64 women with early pregnancy failure. Seven women (11%) did not opt for misoprostol at all, because of fear of pain or bleeding using misoprostol. Fifty percent of the women would prefer misoprostol if its complete evacuation rate exceeds 65%. A majority of women would prefer misoprostol over curettage if its complete evacuation rate exceeds 65%.


[Establishment of diagnostic model to monitor minimal residual disease of acute promyelocytic leukemia by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry].
To screen the potential protein biomarkers in minimal residual disease (MRD) of the acute promyelocytic leukemia (APL) by comparison of differentially expressed serum protein between APL patients at diagnosis and after complete remission (CR) and healthy controls, and to establish and verify a diagnostic model. Serum proteins from 36 cases of primary APL, 29 cases of APL during complete remission and 32 healthy controls were purified by magnetic beads and then analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The spectra were analyzed statistically using FlexAnalysis(TM) and ClinProt(TM) software. Two prediction model of primary APL/healthy control, primary APL/APL CR were developed. Thirty four statistically significant peptide peaks were obtained with the m/z value ranging from 1000 to 10 000 (P < 0.001) in primary APL/healthy control model. Seven statistically significant peptide peaks were obtained in primary APL/APL CR model (P < 0.001). Comparison of the protein profiles between the two models, three peptides with m/z 4642, 7764 and 9289 were considered as the protein biomarker of APL MRD. A diagnostic pattern for APL CR using m/z 4642 and 9289 was established. Blind validation yielded correct classification of 6 out of 8 cases. The MALDI-TOF MS analysis of APL patients serum protein can be used as a promising dynamic method for MRD detection and the two peptides with m/z 4642 and 9289 may be better biomarkers.


Co-localization of hyperphosphorylated tau and caspases in the brainstem of Alzheimer's disease patients.
Hyperphosphorylation of microtubule associated protein tau had limited studies in Alzheimer's disease (AD) brainstem. We compared the distribution and number of neurons with hyperphosphorylated tau in two age groups of AD brainstems with mean ages of 65.4 +/- 5.7 and 91.1 +/- 6.4 years. The degree of co-localization of hyperphosphorylated tau positive cells with either cleaved caspase-3 or cleaved caspase-6 was also quantified. Results showed hyperphosphorylated tau mainly occurred in hypoglossal, dorsal motor vagal, trigeminal sensory/motor nuclei as well as in dorsal raphe, locus coeruleus and substantia nigra. Older AD brainstem consistently had higher density of hyperphosphorylated tau cells. Up to 70% of tau positive cells also displayed either cleaved caspase-3 or caspase-6, and the number of co-localized tau cells in each caspase subfamily group was always higher in older aged group. Some hyperphosphorylated tau cells with cleaved caspases had TUNEL positive nuclei. These findings suggest that these latter cells went through the apoptotic process or DNA fragmentation.


Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients.
One of the 233 polymorphisms associated with multiple sclerosis (MS) susceptibility lies within the NDFIP1 gene, and it was previously identified as eQTL in healthy controls. NDFIP1 shows interesting immune functions and is involved in the development of the central nervous system. We aimed at studying the NDFIP1 variant on activation and metabolism of immune cells. NDFIP1 mRNA and protein expression were assessed in PBMCs by qPCR and western blot in 87 MS patients and 84 healthy controls genotyped for rs4912622. Immune activation after PHA stimulation was evaluated by CD69 upregulation, and metabolic function of both basal and PHA-activated lymphocytes was studied by Seahorse Xfp-Analyzer. In minor-allele homozygous controls but not in patients, we found higher NDFIP1 expression, significantly reduced protein levels, and CD69 upregulation in B- and T-cells. PBMCs from minor-allele homozygous controls showed significantly higher basal mitochondrial respiration and ATP production compared to major-allele carriers, while minor-allele homozygous patients showed significantly lower metabolic activity than carriers of the major allele. In conclusion, we describe associations in minor-allele homozygous controls with lower levels of NDFIP1 protein, CD69 upregulation, and raised mitochondrial activity, which are not replicated in MS patients, suggesting a NDFIP1 differential effect in health and disease.


MicroRNA-661 modulates redox and metabolic homeostasis in colon cancer.
Cancer cell survival and metastasis are dependent on metabolic reprogramming that is capable of increasing resistance to oxidative and energetic stress. Targeting these two processes can be crucial for cancer progression. Herein, we describe the role of microRNA-661 (miR661) as epigenetic regulator of colon cancer (CC) cell metabolism. MicroR661 induces a global increase in reactive oxygen species, specifically in mitochondrial superoxide anions, which appears to be mediated by decreased carbohydrate metabolism and pentose phosphate pathway, and by a higher dependency on mitochondrial respiration. MicroR661 overexpression in non-metastatic human CC cells induces an epithelial-to-mesenchymal transition phenotype, and a reduced tolerance to metabolic stress. This seems to be a general effect of miR661 in CC, since metastatic CC cell metabolism is also compromised upon miR661 overexpression. We propose hexose-6-phosphate dehydrogenase and pyruvate kinase M2 as two key players related to the observed metabolic reprogramming. Finally, the clinical relevance of miR661 expression levels in stage-II and III CC patients is discussed. In conclusion, we propose miR661 as a potential modulator of redox and metabolic homeostasis in CC.


The prevalence and correlates of major and minor depression in older medical inpatients.
To describe the prevalence of and characteristics associated with major and minor depression in older medical inpatients and to compare associated characteristics by sex and history of depression. Cross-sectional study of two patient samples, with and without a screening diagnosis of major or minor depression. The medical services of two acute care hospitals. Medical admissions of people aged 65 and older with at most mild cognitive impairment (N=380). Diagnoses of major and minor depression (Diagnostic Interview Schedule), cognitive impairment (Mini-Mental State Examination), premorbid disability, sociodemographic variables (including social networks and support), comorbidity, severity of illness, history of depression. The prevalence of major depression differed by hospital, ranging from 14.2% (95% confidence interval (CI)=11.7-17.1) in Hospital A to 44.5% (95% CI=33.1-56.4) in Hospital B. The prevalence of minor depression was similar in the two hospitals, ranging from 9.4% (95% CI=7.4-11.9) in Hospital A to 7.9% (95% CI=2.9-16.3) in Hospital B. After adjustment for hospital, the same characteristics (history of depression, premorbid disability, cognitive impairment, perceived adequacy of support, and visits from friends) were associated with major and minor depression, although most of these associations tended to be weaker for minor depression. Most of these factors were also associated with depression in multivariate analyses. The most important characteristics in women were premorbid disability, history of depression, and adequacy of emotional support; in men they were history of depression, cognitive impairment, and adequacy of emotional support. A cerebrovascular or other cardiovascular diagnosis did not explain the association between depression and cognitive impairment. Major and minor depression occur frequently in older medical inpatients and are associated with similar patient characteristics. A history of depression and the patient's sex should be considered in the identification and interpretation of these associated factors.


Protective spin-labeled fluorenes maintain amyloid beta peptide in small oligomers and limit transitions in secondary structure.
Alzheimer's disease is characterized by the presence of extracellular plaques comprised of amyloid beta (Aβ) peptides. Soluble oligomers of the Aβ peptide underlie a cascade of neuronal loss and dysfunction associated with Alzheimer's disease. Single particle analyses of Aβ oligomers in solution by fluorescence correlation spectroscopy (FCS) were used to provide real-time descriptions of how spin-labeled fluorenes (SLFs; bi-functional small molecules that block the toxicity of Aβ) prevent and disrupt oligomeric assemblies of Aβ in solution. Furthermore, the circular dichroism (CD) spectrum of untreated Aβ shows a continuous, progressive change over a 24-hour period, while the spectrum of Aβ treated with SLF remains relatively constant following initial incubation. These findings suggest the conformation of Aβ within the oligomer provides a complementary determinant of Aβ toxicity in addition to oligomer growth and size. Although SLF does not produce a dominant state of secondary structure in Aβ, it does induce a net reduction in beta secondary content compared to untreated samples of Aβ. The FCS results, combined with electron paramagnetic resonance spectroscopy and CD spectroscopy, demonstrate SLFs can inhibit the growth of Aβ oligomers and disrupt existing oligomers, while retaining Aβ as a population of smaller, yet largely disordered oligomers.


Structure analysis of the fourth transmembrane domain of Nramp1 in model membranes.
Nramp1 (natural resistance-associated macrophage protein 1) is an integral membrane protein with 12 putative transmembrane domains. As a proton-coupled divalent metal cation transporter, it is involved in defense against intracellular pathogens. Disease-causing mutation in Nramp1 occurring at glycine 169 located within the fourth transmembrane domain (TM4) suggests functional importance of this domain. In this paper, we study the three-dimensional structures of a peptide, corresponding to the TM4 of the wild-type Nramp1, in SDS micelles and 2, 2, 2-trifluoroethanol solvent using CD and NMR spectroscopies. We have found that an alpha-helix is predominantly induced in membrane-mimetic environments and the folding of the C-terminal residues is regulated by pH in SDS micelles. The peptide is embedded in SDS micelles and self-associated by coiled-coil interactions. The helix of the peptide in TFE is lengthened towards the N-terminus compared with those in SDS micelles at acidic pH and the self-association of the peptide is also observed in TFE. The fact that Mn(2+) ions are accessible to Asp-14 located in the interior of SDS micelles is found and the binding affinity is increased with increasing pH. The self-association of the peptide may provide a path by which Mn(2+) ions pass through the membrane.


Understanding capacity fade in organic redox-flow batteries by combining spectroscopy with statistical inference techniques.
Organic redox-active molecules are attractive as redox-flow battery (RFB) reactants because of their low anticipated costs and widely tunable properties. Unfortunately, many lab-scale flow cells experience rapid material degradation (from chemical and electrochemical decay mechanisms) and capacity fade during cycling (>0.1%/day) hindering their commercial deployment. In this work, we combine ultraviolet-visible spectrophotometry and statistical inference techniques to elucidate the Michael attack decay mechanism for 4,5-dihydroxy-1,3-benzenedisulfonic acid (BQDS), a once-promising positive electrolyte reactant for aqueous organic redox-flow batteries. We use Bayesian inference and multivariate curve resolution on the spectroscopic data to derive uncertainty-quantified reaction orders and rates for Michael attack, estimate the spectra of intermediate species and establish a quantitative connection between molecular decay and capacity fade. Our work illustrates the promise of using statistical inference to elucidate chemical and electrochemical mechanisms of capacity fade in organic redox-flow battery together with uncertainty quantification, in flow cell-based electrochemical systems.


L-Lactate-selective microbial sensor based on flavocytochrome b2-enriched yeast cells using recombinant and nanotechnology approaches.
In the recent years, nanotechnology is the most developing branch due to a wide variety of potential applications in biomedical, biotechnological and agriculture fields. The binding nanoparticles with various biological molecules makes them attractive candidates for using in sensor technologies. The particularly actual is obtaining the bionanomembranes based on biocatalytic elements with improved sensing characteristics. The aim of this investigation is to study the properties of microbial L-lactate-selective sensor based on using the recombinant Hansenula polymorpha yeast cells overproducing flavocytochrome b2 (FC b2), as well as additionally enriched by the enzyme bound with gold nanoparticles (FC b2-nAu). Although, the high permeability of the living cells to nanoparticles is being intensively studied (mostly for delivery of drugs), the idea of using both recombinant technology and nanotechnology to increase the amount of the target enzyme in the biosensing layer is really novel. The FC b2-nAu-enriched living and permeabilized yeast cells were used for construction of a bioselective membrane of microbial L-lactate-selective amperometric biosensor. Phenazine methosulphate was served as a free defusing electron transfer mediator which provides effective electron transfer from the reduced enzyme to the electrode surface. It was shown that the output to L-lactate of FC b2-nAu-enriched permeabilized yeast cells is 2.5-fold higher when compared to the control cells. The obtained results confirm that additional enrichment of the recombinant yeast cell by the enzyme bound with nanoparticles improves the analytical parameters of microbial sensor.


A knowledge-integrated deep learning framework for cellular image analysis in parasite microbiology.
Cellular image analysis is an important method for microbiologists to identify and study microbes. Here, we present a knowledge-integrated deep learning framework for cellular image analysis, using three tasks as examples: classification, detection, and reconstruction. Alongside thorough descriptions of different models and datasets, we describe steps for computing environment setup, knowledge representation, data pre-processing, and training and tuning. We then detail evaluation and visualization. For complete details on the use and execution of this protocol, please refer to Li et al. (2021),1 Jiang et al. (2020),2 and Zhang et al. (2022).3.


Nonstrict and individual enhanced recovery after surgery (ERAS) in partial hepatectomy.
We aimed to evaluate postoperative recovery and short-term outcomes of patients undergoing partial hepatectomy managed with a nonstrict and individual enhanced recovery after surgery (ERAS) program. A retrospective analysis of 168 partial hepatectomy patients in our institution was included. The discharged day and the respective impact of element application throughout the duration were analyzed. When all the required elements of ERAS were fully implemented, the median discharge day was 6. The more deviation occurred, the more delayed the patient discharged (P < 0.01). Preoperative ASA score, basic conditions of patients and ages were revealed closely associated with discharge day (P < 0.001). Without or an early removal of tubes and early oral feeding reduced hospital stay statistically (P < 0.01). Early discharge of patients (<3 days) did not show an increased complication incidence or readmission (P > 0.05). Nonstrict and individual use of ERAS in partial hepatectomy reduced postoperative length of stay without increasing complication rate. Our study proposes a modulation of ERAS according to the needs and acceptance of patients. In a word, better optionally required rather than mandatorily meet.


Incidence and prevalence of coccidioidomycosis in patients with end-stage liver disease.
Coccidioidomycosis is an endemic fungal infection of the desert southwestern United States. Patients with end-stage liver disease (ESLD) have not been described as having a high rate of coccidioidal infection. We prospectively evaluated 290 patients with ESLD for liver transplantation and found that 6 of these patients (2.1%) had active coccidioidal infection at presentation. Of 184 patients listed for transplantation, 48 patients were observed for at least 1 year; among these 48 patients, new coccidioidal infection developed in 2 patients within the year, for a 1-year incidence of 4.2%. Conversely, the incidence of coccidioidal infection in Maricopa County, Arizona in that same period was 0.04%. Awareness is needed to identify the presence of coccidioidal infection, which may be masked by symptoms and findings of ESLD. Treatment may alleviate some of the symptoms of coccidioidomycosis originally attributed to the concomitant liver disease.


Colorectal Intussusception with an Invasive Adenocarcinoma as Lead Point.
Teaching Point: Always look for an underlying (malignant) lead point as cause of a large bowel intussusception in adults.


COVID-19 infection in solid organ transplant recipients: A single-center experience with patients immediately after transplantation.
In our transplant center, infection with SARS-CoV-2 virus was confirmed in 4 organ transplant recipients (3 kidney and 1 liver transplant recipients) during their early post-transplant hospital stay. In this paper, we report the basic characteristics, management, clinical course, and outcomes of these patients.


Molecular regulation of Na+-K+-2Cl- cotransporter (NKCC1) and epithelial chloride secretion.
Defective regulation of epithelial secretion underlies the clinical manifestations of a number of important human diseases ranging from cystic fibrosis to secretory diarrhea. Although much attention has focused on the role of apical membrane chloride (Cl-) channels in this process, emerging evidence highlights the importance of a basolateral Na+-K+-2Cl- cotransporter (NKCC1) as an independent regulatory site that may determine the overall rate of epithelial secretion. The cotransporter NKCC1 is expressed not only in epithelial cells but also in virtually all mammalian cells, where it plays a more generalized role in cell volume homeostasis, cell ionic composition, and, possibly, the control of cell growth. Emerging molecular evidence indicates that NKCC1 function is regulated in the short and long term at the level of protein phosphorylation, membrane targeting, and gene expression. An improved understanding of NKCC1 may lead to new therapeutic approaches to secretory diarrhea as well as diverse clinical conditions in which cell ion composition is disturbed.


Insulin receptor tyrosine kinase activity and phosphorylation of tyrosines 1162 and 1163 are required for insulin-increased prolactin gene expression.
Insulin treatment increased prolactin gene expression in GH4 cells, a rat pituitary tumor cell line, through the endogenous insulin receptor. However, insulin regulation of transfected plasmids required the expression of cotransfected insulin receptor. Prolactin-CAT expression was increased 12-fold in cells transfected with wild type insulin receptor, but insulin did not increase prolactin gene expression when a kinase negative mutant of the ATP binding site (K1030R) was expressed. Thus, receptor kinase activity was required for signaling to gene transcription. Mutation of tyrosine 1158 did not reduce insulin-increased prolactin-CAT expression while individual mutations of tyrosine 1162 and tyrosine 1163 each reduced insulin-increased prolactin-CAT expression by 50% and a triple mutant of tyrosines 1158/1162/1163 was inactive. Thus, mutation of tyrosine 1162 and 1163 was also sufficient to inactivate signaling by the insulin receptor. Insulin-stimulated auto phosphorylation occurred in all mutants in vitro except the ATP binding site mutant. However, the ability of mutant insulin receptors to mediate insulin-increased prolactin-CAT expression correlated with the substrate-specific catalytic activity of the receptors. This suggested that phosphorylation of these tyrosines was important for substrate access to the catalytic domain of the receptor.


Use of Camelina sativa and By-Products in Diets for Dairy Cows: A Review.
Camelina sativa, belonging to the Brassicaceae family, has been grown since 4000 B.C. as an oilseed crop that is more drought- and cold-resistant. Increased demand for its oil, meal, and other derivatives has increased researchers' interest in this crop. Its anti-nutritional factors can be reduced by solvent, enzyme and heat treatments, and genetic engineering. Inclusion of camelina by-products increases branched-chain volatile fatty acids, decreases neutral detergent fiber digestibility, has no effect on acid detergent fiber digestibility, and lowers acetate levels in dairy cows. Feeding camelina meal reduces ruminal methane, an environmental benefit of using camelina by-products in ruminant diets. The addition of camelina to dairy cow diets decreases ruminal cellulolytic bacteria and bio-hydrogenation. This reduced bio-hydrogenation results in an increase in desirable fatty acids and a decrease in saturated fatty acids in milk obtained from cows fed diets with camelina seeds or its by-products. Studies suggest that by-products of C. sativa can be used safely in dairy cows at appropriate inclusion levels. However, suppression in fat milk percentage and an increase in trans fatty acid isomers should be considered when increasing the inclusion rate of camelina by-products, due to health concerns.


Use of the carbon dioxide laser in the management of orbital plexiform neurofibromas.
We present one of three cases in which we have used the carbon dioxide laser to successfully perform subtotal surgical removal of plexiform neurofibromas of the lid and orbit.