Evaluating the Effect of Oblique Ridge Conservation on Stress Distribution in an Endodontically Treated Maxillary First Molar: A Finite Element Study.
Although the maxillary first molar (MFM) has been frequently subjected to stress analysis in endodontic investigations, the available data about the effect of its oblique ridge are quite sparse. The aim of this study includes evaluating the effect of the residual oblique ridge on the stress distribution after preparing conservative access cavities. Based on the cone-beam computed tomographic data, the model of an intact MFM and 5 cavity designs were prepared for endodontic treatment, which were consequently filled with gutta-percha and dental resin composite (6 total models). All models were subjected to 4 types of occlusal loading; finite element analysis via ABAQUS CAE software (Dassault Systemes, Vélizy-Villacoublay, France) was accomplished, whereas other software programs such as (Mimics Research Materialise, Leuven, Belgium) and 3-Matic Research (Materialise) were also incorporated in different stages for detecting stress distribution. The stress distribution on the MFM is not only dependent on the remaining width of the oblique ridge but also on the type of loading. The most stress on the cervical region was concentrated on the palatal root in some type of loading, whereas the least stress on the occlusal surface was recorded when the whole oblique ridge was replaced by the composite resin. When the occlusal contacts are occurring only on the palatal cusp, the stress distribution on the oblique ridge is noticeably affected by the cavity design.


Propofol inhibits myocardial injury induced by microvesicles derived from hypoxia-reoxygenated endothelial cells via lncCCT4-2/CCT4 signaling.
Ischemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms. Hypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay. In vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-injured cardiomyocytes compared to HR-EMVs. Mechanistically, RNA sequencing of EMVs and RT-qPCR showed that lncCCT4-2 was significantly upregulated in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs. Reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. Furthermore, the anti-apoptotic activity of lncCCT4-2 from (HR + P)-EMVs was achieved by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in cardiomyocytes. Our study showed that (HR + P)-EMVs uptake by IR-injured cardiomyocytes upregulated lncCCT4-2 in cardiomyocytes and promoted CCT4 expression, thereby inhibiting HR-EMVs induced oxidative stress and apoptosis.


Genome-wide transcriptomic comparison of cotton (Gossypium herbaceum) leaf and root under drought stress.
In this study, the 454 pyrosequencing platform was used for analyzing the comparative transcriptomic profiles of leaf and root tissues of 1-month-old cotton (Gossypium herbaceum) plants under drought stress. A total of 56,354 and 49,308 reads were generated from leaf and root tissues, respectively, and clustered into 6,313 and 5,858 unigenes. The differentially expressed unigenes that showed up-regulation (≥2-fold) or down-regulation (2≤-fold) were considered for further analysis. A total of 3,517 unigenes were differentially expressed in both tissues. The 1,528 genes specific to leaves and 1,128 specific to roots were obtained. The 28 biological pathways in two tissues were found to respond significantly to drought stress. A total of 289 in leaf and 277 in root unknown (novel) unigenes were found to be remarkably regulated by drought stress. Some key regulatory genes involved in abiotic stress such as WRKY, ERF, AP2 EREBP, MYB, and LEA were highly expressed in leaves. The genes RHD3, LBD, and transcription factor WRKY75, known for root development under various stress conditions, were expressed specifically in root. The genes related to chlorophyll a/b binding protein and photosystem-related proteins showed significant higher expression in roots and as compared to leaves. It can be concluded that cotton leaves are distinct from roots in terms of molecular mechanisms for responses to drought stress.


Functional importance of the D614G mutation in the SARS-CoV-2 spike protein.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus which binds its cellular receptor angiotensin-converting enzyme 2 (ACE2) and enters hosts cells through the action of its spike (S) glycoprotein displayed on the surface of the virion. Compared to the reference strain of SARS-CoV-2, the majority of currently circulating isolates possess an S protein variant characterized by an aspartic acid-to-glycine substitution at amino acid position 614 (D614G). Residue 614 lies outside the receptor binding domain (RBD) and the mutation does not alter the affinity of monomeric S protein for ACE2. However, S(G614), compared to S(D614), mediates more efficient ACE2-mediated transduction of cells by S-pseudotyped vectors and more efficient infection of cells and animals by live SARS-CoV-2. This review summarizes and synthesizes the epidemiological and functional observations of the D614G spike mutation, with focus on the biochemical and cell-biological impact of this mutation and its consequences for S protein function. We further discuss the significance of these recent findings in the context of the current global pandemic.


Examining the relationship of concurrent obesity and tobacco use disorder on the development of substance use disorders and psychiatric conditions: Findings from the NESARC-III.
Multimorbidity is linked to worse health outcomes than single health conditions. However, recent studies show that obesity may reduce the risk of developing substance use disorders (SUDs), particularly in vulnerable populations. We investigated how comorbid obesity and tobacco use disorder (TUD) relate to the risk of SUDs and psychiatric conditions. Data was used from 36,309 individuals who completed the National Epidemiological Survey on Alcohol and Related Conditions - Wave III. Individuals who met the DSM-5 criteria for TUD in the last year were defined as the TUD group. Obesity was defined as having a body mass index (BMI) greater than 30 kg/m2. Using this information, individuals were grouped into categories, with people being identified as either having obesity, TUD, both obesity and TUD, or not having either obesity or TUD (comparison). Groups were compared against their comorbid diagnoses of either an additional SUD or psychiatric conditions. Controlling for demographic characteristics, we found that individuals with obesity including those individuals with TUD, had lower rates of comorbid SUD diagnosis than individuals with TUD alone. Additionally, individuals with combined TUD and obesity, and those with TUD alone, had the highest rates of comorbid psychiatric disorder diagnosis. The current study aligns with previous research suggesting that obesity may reduce risk of substance use disorders, even in individuals who have other risk factors promoting harmful substance use (e.g., tobacco use). These findings may inform targeted intervention strategies for this clinically relevant subpopulation.


The pedicled 'policeman' flap salvage of exposed vascular prosthesis - a case report.
A case report of a patient with exposed, infected, subcutaneous, extra-anatomical, vascular prosthesis is presented, which was successfully salvaged using pedicled omental flap after other reconstructive procedures had failed.


Aldosterone receptor antagonism in heart failure.
The renin-angiotensin-aldosterone system plays a major role in the pathophysiology of heart failure. Aldosterone is one of the central mediators involved in the cardiac remodeling process. Its classic effect in heart failure is attributed to mineralocorticoid receptor-mediated salt and fluid retention leading to increased afterload. New evidence demonstrates nonclassic effects of increased collagen synthesis and myocardial fibrosis resulting in left ventricular hypertrophy. Antagonism of aldosterone receptors with spironolactone benefits patients with severe heart failure, and eplerenone benefits those after myocardial infarction who have left ventricular dysfunction. Future research is directed at aldosterone antagonism in patients with mild-to-moderate heart failure, coronary artery disease treated with percutaneous coronary intervention, and nephropathy complicated by diabetes mellitus.


Visual object detection biases escape trajectories following acoustic startle in larval zebrafish.
In this study, we investigated whether the larval zebrafish is sensitive to the presence of obstacles in its environment. Zebrafish execute fast escape swims when in danger of predation. We posited that collisions with solid objects during escape would be maladaptive to the fish, and therefore, the direction of escape swims should be informed by the locations of barriers. To test this idea, we developed a closed-loop imaging rig outfitted with barriers of various qualities. We show that when larval zebrafish escape in response to a non-directional vibrational stimulus, they use visual scene information to avoid collisions with obstacles. Our study demonstrates that barrier avoidance rate corresponds to the absolute distance of obstacles, as distant barriers outside of collision range elicit less bias than nearby collidable barriers that occupy the same amount of visual field. The computation of barrier avoidance is covert: the fact that fish will avoid barriers during escape cannot be predicted by its routine swimming behavior in the barrier arena. Finally, two-photon laser ablation experiments suggest that excitatory bias is provided to the Mauthner cell ipsilateral to approached barriers, either via direct excitation or a multi-step modulation process. We ultimately propose that zebrafish detect collidable objects via an integrative visual computation that is more complex than retinal occupancy alone, laying a groundwork for understanding how cognitive physical models observed in humans are implemented in an archetypal vertebrate brain. VIDEO ABSTRACT.


Utility of extracellular vesicles as a potential biological indicator of physiological resilience during military operational stress.
Extracellular vesicles (EVs) transport biological content between cells to mediate physiological processes. The association between EVs and resilience, the ability to cope with stress, is unknown. Using unbiased machine learning approaches, we aimed to identify a biological profile of resilience. Twenty servicemen (27.8 ± 5.9 years) completed the Connor Davidson Resilience (CD-RISC) questionnaire and were exposed to daily physical and cognitive exertion with 48-hr sleep and caloric restriction. Blood samples from baseline and the second day of stress were analyzed for neuroendocrine biomarkers impacted by military stress. EVs were isolated from plasma and stained with antibodies associated with exosomes (CD63), microvesicles (VAMP3), and apoptotic bodies (THSD1). Individuals were separated into high (n = 10, CD-RISC > 90) and low (n = 10, CD-RISC < 79) resilience. EV features were stratified by size, then down-selected using regression trees and compared between groups. Diagnostic accuracy was assessed using receiver operating characteristic curves. Compared to low resilience, high resilience demonstrated a greater increase in variability of THSD1 local bright spot intensities among large-sized EVs in response to stress (p = 0.002, Hedges' g = 1.59). Among medium-sized EVs, high resilience exhibited a greater decrease in side scatter intensity (p = 0.014, Hedges' g = 1.17). Both features demonstrated high to moderate diagnostic accuracy for high resilience (AUC = 0.90 and 0.79). In contrast, neuroendocrine biomarker concentrations were similar between groups. The increase in variability among THSD1 + EVs in high, but not low, resilient individuals following stress may suggest high resilience is accompanied by stress-triggered apoptotic adaptations to the environment that are not detected in neuroendocrine biomarkers.


Long-term safety and effectiveness of adalimumab in Japanese patients with Crohn's disease: 3-year results from a real-world study.
Crohn's disease is a chronic disorder; therefore, it is essential to investigate long-term safety and efficacy of treatments. This study assessed the safety and effectiveness of adalimumab for up to 3 years in Japanese patients with Crohn's disease in real-world settings. This was a multicenter, single-cohort, observational study of patients with Crohn's disease. Safety assessments included incidence of adverse drug reactions. Effectiveness assessments included clinical remission, mucosal healing, and Work Productivity and Activity Impairment (WPAI). The safety and effectiveness analysis populations comprised 389 and 310 patients, respectively. Mean (standard deviation) exposure to adalimumab in the safety analysis population was 793.4 (402.8) days, with a 58.1% retention rate. A total of 105 patients (27.0%) and 43 patients (11.1%) experienced adverse drug reactions and serious adverse drug reactions, respectively, with no patient reporting tuberculosis or hepatitis B. Infections and serious infections were reported in 37 patients (9.5%) and 17 patients (4.4%), respectively. Malignancy was reported as an adverse drug reaction in 2 patients (0.5%). Remission rate increased from 37.8% (98/259) at baseline to 73.9% (167/226) at week 4 and remained > 70% over 3 years. Proportion of patients without mucosal ulcerations increased from 2.7% (2/73) at baseline to 42.3% (11/26) between years > 2 to ≤ 3. WPAI improvement started at 4 weeks, with the overall work impairment score improving from 42.7 (n = 102) at baseline to 26.9 (n = 84) at 4 weeks. Results from this study confirm the long-term safety and effectiveness of adalimumab treatment in Japanese patients with Crohn's disease in the real-world setting.


Alberta dairy farmers' and veterinarians' opinion about bovine leukemia virus control measures.
A high herd and within-herd prevalence of Bovine Leukemia Virus (BLV) infections in the dairy herds of North America and the negative effects thereof caused the Alberta dairy industry to initiate the development of an on farm BLV control program. Because BLV control is dependent on the commitment of the farmer, potential barriers were identified and farmers' and veterinarians' points of view toward different control options were investigated to inform how the control program might be adjusted. Conversations with these stakeholders were sought and four focus groups with farmers and eleven interviews with veterinarians were conducted. Testing for BLV, the most common BLV control strategies (testing/culling/segregation/management), as well as on farm best management practices (BMP) to prevent the transmission of BLV, were discussed. The thematic analysis of these conversations resulted in the following findings: Testing of animals was considered important for BLV control, but the financial investment was prohibitive for farmers. Test and cull as well as test and segregation approaches of test positive animals were considered efficient BLV control measures, but impractical and not feasible due to the supply managed Alberta dairy industry (i.e. milk is produced based on demand), with a high prevalence. The management of test positive animals with BMP to prevent new infections and thereby decreasing the within-herd prevalence was considered the only realistic BLV control strategy. The most important barriers for suggested BMP were the cost for some BMP, the inconvenience of performing other BMP, as well as difficulties in performing some BMP consistently and well. Additionally, a lack of knowledge about BLV and its control were identified as an important barrier. On the contrary, farmers indicated being inclined to implement BMP they considered feasible or that were considered a standard within the industry. Further, if BMP increased convenience on farm, they were considered easy to implement. Farmers and veterinarians agreed in many, but not all cases. For example, the single use of examination sleeves was met with differing opinions (i.e. considered doable by farmers while veterinarians assumed it to be too costly). In conclusion, stakeholders' awareness and communication amongst each other (e.g. veterinarians and farmers) about BLV and its control has to be highlighted in order to manage BLV infection successfully. In addition, by communicating and understanding barriers and motivators for specific BMP, important barriers could be identified (e.g. difficulties while changing needles), and solutions found (e.g. tool belt for needles), thereby improving BLV control efforts on farm.


Mechanical frequency detection thresholds in the human face.
Afferent information originating from mechanoreceptors located within perioral facial skin is considered to play an important role in the development and maintenance of fine motor skill associated with the production of speech. To date, little quantitative information is available on the frequency sensitivity of the face to controlled sinusoidal displacements, especially in areas of tissue that change shape during speech. The purpose was to determine the mechanical frequency detection thresholds of select skin sites in the face and hand using a psychophysical procedure. Mean frequency detection thresholds for all facial skin sites were significantly higher than thresholds for the forefinger. Further, pacinian-type frequency sensitivity, characteristic of the finger, was absent in the face. Finally, vibratory stimuli may be useful in the assessment of skin sense in patients with suspected involvement of the trigeminal system. A case study is presented to highlight the quantitative nature of this psychophysical procedure.


Partial monosomy 13 and 21 due to a familial 13/21 translocation.
Two patients are described with a monosomy for the proximal part of the long are of chromosome 13 and for the distal part of the long arm of chromosome 21, due to an unbalanced 13/21 translocation.


Occupational stress, job satisfaction and job performance among hospital nurses in Kampala, Uganda.
To assess levels of occupational stress, job satisfaction and job performance among hospital nurses in Kampala, Uganda; and how they are influenced by work and personal characteristics. Occupational stress is reported to affect job satisfaction and job performance among nurses, thus compromising nursing care and placing patients' lives at risk. Although these factors have been studied extensively in the US and Europe, there was a need to explore them from the Ugandan perspective. A correlational study was conducted with 333 nurses from four hospitals in Kampala, Uganda. A questionnaire measuring occupational stress, job satisfaction and job performance was used. Data were analysed using descriptive statistics and anova. There were significant differences in levels of occupational stress, job satisfaction and job performance between public and private not-for-profit hospitals, nursing experience and number of children. Organizational differences between public and private not-for-profit hospitals influence the study variables. On-the-job training for nurse managers in human resource management to increase understanding and advocacy for organizational support policies was recommended. Research to identify organizational, family or social factors which contribute to reduction of perceived occupational stress and increase job satisfaction and job performance was recommended.


Nasopharyngeal carcinoma: posttreatment changes of imaging findings.
The purpose of this study was to determine the radiologic results of nasopharyngeal carcinoma (NPC) that showed complete responses on follow-up imaging studies after radiation therapy. This study is a retrospective review of 23 patients (18 male, 5 female, aged 15-71 years; mean age, 48.5 years) affected with NPC, from August 1995 to July 2000, who were examined with magnetic resonance imaging or computed tomography scan before and after either radical radiotherapy or chemoradiotherapy. The median follow-up was 24.7 months and ranged from 12 to 48 months. We analyzed the primary tumors by ascertaining/measuring tumor size, depth, middle ear effusion, skull base invasion, and lymphadenopathy. The treatment responses for primary tumors were classified as either atrophy, scar (asymmetric elevation without enhancement), or normalized. The tumor response and the appearance of bone regeneration in the previous destructive part of the skull base were also recorded. The 23 patients consisted of 12 superficial tumors, for whom treatment results were normalized in 10, atrophy in 1, and scar in 1 and 11 deep tumors for whom treatment results were scar in 6, normalized in 3, and atrophy in 2. Skull base invasion was detected in 6 patients, 5 of whom showed complete healing of skull base destruction after radiotherapy. However, the other patient exhibited an unusual hyperostotic change in the skull base mimicking fibrous dysplasia of the skull base. The superficial tumors tended to be radiologically normalized even when they were large. However, the deep tumors mainly changed to scar after radiation therapy. On the other hand, skull base invasion could be normalized after radiotherapy.


Trypanosoma brucei: analysis of relapsing populations in sensitive and resistant breeds of cattle.
The clone DiTat 1.1 of Trypanosoma brucei brucei was injected into four bovids, and clones obtained from successive waves of parasitemia were used to study the expressed variant-specific surface glycoprotein repertoire. Twenty-four clones were obtained which could be classified into 12 different variable antigen types, in addition to the clone injected, using agglutination or immunofluorescence with monospecific antisera. The variable surface glycoproteins of the 25 clones were extracted using the detergent octyl-beta-D-glucopyranoside in the presence of the protease inhibitor, N-cbz-L-phenylalaninechloromethylketone. The molecular weights varied from 52,000 to 69,000 and the pI from 5.0 to 8.8. The virulence of 14 clones representing 13 variable antigen types was ascertained in mice. The mean survival time ranged from 20.5 to 43.0 days. Clones isolated from early peaks of parasitemia in the bovid were the most virulent while clones derived from later peaks were less virulent. It seems that organisms of diminishing virulence appear in bovids, leading to self-cure of the disease. All clones were sensitive to human serum in a blood infectivity inhibition test. Antibody against all virulent clones appeared in 20 cattle (10 Zebus, 10 Baoulés) which had been injected with T. brucei DiTat 1.1. There was no evidence for parasites of high or low virulence being preferentially expressed in resistant or sensitive hosts.


Comparing high-dimensional confounder control methods for rapid cohort studies from electronic health records.
Electronic health records (EHR), containing rich clinical histories of large patient populations, can provide evidence for clinical decisions when evidence from trials and literature is absent. To enable such observational studies from EHR in real time, particularly in emergencies, rapid confounder control methods that can handle numerous variables and adjust for biases are imperative. This study compares the performance of 18 automatic confounder control methods. Methods include propensity scores, direct adjustment by machine learning, similarity matching and resampling in two simulated and one real-world EHR datasets. Direct adjustment by lasso regression and ensemble models involving multiple resamples have performance comparable to expert-based propensity scores and thus, may help provide real-time EHR-based evidence for timely clinical decisions.


Transient active zone remodeling in the Drosophila mushroom body supports memory.
Elucidating how the distinct components of synaptic plasticity dynamically orchestrate the distinct stages of memory acquisition and maintenance within neuronal networks remains a major challenge. Specifically, plasticity processes tuning the functional and also structural state of presynaptic active zone (AZ) release sites are widely observed in vertebrates and invertebrates, but their behavioral relevance remains mostly unclear. We here provide evidence that a transient upregulation of presynaptic AZ release site proteins supports aversive olfactory mid-term memory in the Drosophila mushroom body (MB). Upon paired aversive olfactory conditioning, AZ protein levels (ELKS-family BRP/(m)unc13-family release factor Unc13A) increased for a few hours with MB-lobe-specific dynamics. Kenyon cell (KC, intrinsic MB neurons)-specific knockdown (KD) of BRP did not affect aversive olfactory short-term memory (STM) but strongly suppressed aversive mid-term memory (MTM). Different proteins crucial for the transport of AZ biosynthetic precursors (transport adaptor Aplip1/Jip-1; kinesin motor IMAC/Unc104; small GTPase Arl8) were also specifically required for the formation of aversive olfactory MTM. Consistent with the merely transitory increase of AZ proteins, BRP KD did not interfere with the formation of aversive olfactory long-term memory (LTM; i.e., 1 day). Our data suggest that the remodeling of presynaptic AZ refines the MB circuitry after paired aversive conditioning, over a time window of a few hours, to display aversive olfactory memories.


Reduced numbers of circulating endothelial progenitor cells in patients with coronary artery disease associated with long-term statin treatment.
While statin treatment may transiently mobilize endothelial progenitor cells (EPCs), the dose-dependent effects of a continuous statin therapy on EPCs in patients with chronic coronary artery disease (CAD) have not been analyzed. In 209 patients with angiographically documented CAD, 144 of which received 10-40 mg/day of statins for >8 weeks, the EPC number was determined by flow cytometry directly (CD34(+)/KDR(+), n=58) and after in vitro-culture (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled Ac-LDL (DiI-Ac-LDL(+))/lectin(+), n=209). EPC function was assessed by the formation of colony forming units (CFUs). Univariate analysis revealed that the dose of continuous statin therapy inversely correlated with the EPC number. Treatment with 40 mg/day significantly reduced EPC counts. Multivariate analysis unveiled the statin dose and extent of CAD as independent predictors of reduced EPC numbers. Conversely, obesity predicted increased counts, while CFU development was not detectable in all patients and augmented in females and smokers but not in statin-treated patients. Compared with matched controls, statin-treated patients showed significantly reduced absolute and relative EPC counts. In a prospective analysis, initiation of statin therapy significantly diminished the number of circulating and isolated EPCs after 3 but not after 1 month(s). Thus, the statin dose during chronic and continuous treatment independently predicts reduced numbers of circulating as well as isolated EPCs in patients with CAD.


Differential expression of estrogen receptor mRNA splice variants in the tamoxifen resistant human breast cancer cell line, MCF-7/TAMR-1 compared to the parental MCF-7 cell line.
Breast cancer patients with an estrogen receptor (ER) positive tumor can be treated with the anti-estrogen tamoxifen, but development of anti-estrogen resistance is a serious problem. We have analyzed a tamoxifen resistant human breast cancer cell line MCF-7/TAMR-1 for alterations in ER which might explain the tamoxifen resistance. The MCF-7/TAMR-1 cells expressed both wild-type ER mRNA and protein, and by RT-PCR we were able to clone ER cDNAs corresponding to the following mRNA splice variants: ER delta E2, ER delta E4, ER delta E5, ER delta E7 and a new double splice variant lacking both exon 4 and 7 (ER delta E4,7) The existence of the ER delta E4,7 variant was confirmed by RNase protection assay. Semi-quantitative RT-PCR revealed that ER delta E2 mRNA was expressed at a higher level in MCF-7/TAMR-1 cells, whereas the ER delta E5 mRNA was expressed at a significantly lower level in MCF-7/TAMR-1 cells compared with MCF-7 cells. The differential expression of the two ER mRNA splice variants indicates that they may be involved in anti-estrogen resistance, although the present knowledge of their biological function does not provide us with an explanation.


Cholinergic mechanisms involved in head-shaking of infant rats.
Central cholinergic mechanisms involved in D-amphetamine induced head-shaking (H-S) were explored in 9-day-old albino rats using anticholinergic, anticholinesterase and cholinomimetic drugs. Scopolamine (5 mg/kg, IP) blocks both spontaneous and D-amphetamine induced H-S. Physostigmine (0.10 mg/kg, IP), but not neostigmine, increases D-amphetamine induced H-S up to 400%. Pilocarpine (1-10 mg/kg, IP) per se induces H-S and strongly potentiates the amphetamine H-S effect. Cholinergic--catecholaminergic interactions in the CNS are discussed in relation to the expression of this motor item.


Relationship and career challenges faced by people infected with HIV in Malaysia.
Background: This study was completed at two general hospitals in Malaysia that provide treatment for HIV patients. The aim of the study was to explore the experiences of people infected with HIV (PIWH) and how they cope with HIV. Methods: This qualitative study was based on a social constructivist and grounded theory approach. A total of 12 PIWH were selected by purposive sampling, all of whom participated in semi-structured and audio-recorded interviews, which were supported with non-participant observations and diary entries on three occasions for each participant. The interviews and diaries were transcribed and analysed using the grounded theory approach, which was assisted by utilizing NVIVO-8 to identify the themes related to the experiences of the participants. Results: PIWH experienced challenges related to their career and relationships with family and others. These challenges led to difficulties in gaining employment and career development, as well as feelings of denial, being uncomfortable, rejection, and labelling. They found that their lives were totally and dramatically changed after being tested positive for HIV. Conclusions: Among PIWH, HIV impacted relationships with significant others and career development. The absence of support and acceptance from significant others affected the ability of PIWH to cope with their daily challenges. The results of this study have implications for policymakers in terms of gaining sufficient knowledge and awareness to provide prevention programmes for HIV/AIDS.


Risk factors associated with peritoneal carcinomatosis of gastric cancer in staging laparoscopy: A systematic review and meta-analysis.
The optimal indications of staging laparoscopy in gastric cancer to detect peritoneal carcinomatosis are still controversial. We performed this systematic review and meta-analysis to quantify the relevance of the preoperative factors with peritoneal carcinomatosis to explore the indications of staging laparoscopy. Systematic searches were conducted using Medline, Embase, and the Cochrane Library in December 2021. On the basis of calculating the odds ratio (OR) of each factor, we quantified the association between the risk factors and peritoneal carcinomatosis such as clinical T/N stage, Borrmann type, and tumor markers, using meta-analysis with a random-effects model. A total of 21 case-control studies and one cohort study were obtained. T stage, N stage, and differentiation degree were most widely studied, with OR values of 2.96 (95% CI: 1.87-4.69), 1.22 (95% CI: 0.86-1.73), and 1.91 (95% CI: 1.42-2.56), respectively. Among all the factors, elevated CA125 (OR = 19.45, 95% CI: 4.71-80.30), Borrmann type IV (OR = 7.68, 95% CI: 3.62-16.27), and large tumor diameter (OR = 5.12, 95% CI: 2.55-10.31) had the highest OR. In particular, CA125 had the best predictability for peritoneal carcinomatosis but was only mentioned by three articles. There was a cognitive gap between the awareness and importance of risk factors for peritoneal carcinomatosis. In addition to T4 stage, patients with factors with high OR, such as Borrmann type IV, large tumor diameter, and elevated CA125, should undergo staging laparoscopy.


Should we routinely test for simultaneous location and scale changes?
It is argued that in many circumstances, there is no compelling reason to believe that measurements from several experimental groups have the same variability. If it is plausible that the variabilities may differ, a statistical test sensitive to changes of scale as well as to changes of location should be selected. Some references to such tests are given.


The importance of glucose-dependent insulinotropic polypeptide receptor activation for the effects of tirzepatide.
Tirzepatide is a unimolecular co-agonist of the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors recently approved for the treatment of type 2 diabetes by the US Food and Drug Administration and the European Medicine Agency. Tirzepatide treatment results in an unprecedented improvement of glycaemic control and lowering of body weight, but the contribution of the GIP receptor-activating component of tirzepatide to these effects is uncertain. In this review, we present the current knowledge about the physiological roles of the incretin hormones GLP-1 and GIP, their receptors, and previous results of co-targeting the two incretin hormone receptors in humans. We also analyse the molecular pharmacological, preclinical and clinical effects of tirzepatide to discuss the role of GIP receptor activation for the clinical effects of tirzepatide. Based on the available literature on the combination of GLP-1 and GIP receptor activation, tirzepatide does not seem to have a classical co-activating mode of action in humans. Rather, in vitro studies of the human GLP-1 and GIP receptors reveal a biased GLP-1 receptor activation profile and GIP receptor downregulation. Therefore, we propose three hypotheses for the mode of action of tirzepatide, which can be addressed in future, elaborate clinical trials.


An Agreement of Antigen Tests on Oral Pharyngeal Swabs or Less Invasive Testing With Reverse Transcription Polymerase Chain Reaction for Detecting SARS-CoV-2 in Adults: Protocol for a Prospective Nationwide Observational Study.
The SARS-CoV-2 pandemic has resulted in an unprecedented level of worldwide testing for epidemiologic and diagnostic purposes, and due to the extreme need for tests, the gold-standard Reverse Transcription Polymerase Chain Reaction (RT-PCR) testing capacity has been unable to meet the overall worldwide testing demand. Consequently, although the current literature has shown the sensitivity of rapid antigen tests (RATs) to be inferior to RT-PCR, RATs have been implemented on a large scale without solid data on performance. This study will compare analytical and clinical sensitivities and specificities of 50 lateral flow- or laboratory-based RATs and 3 strand invasion-based amplification (SIBA)-RT-PCR tests from 30 manufacturers to RT-PCR testing of samples obtained from the deep oropharynx. In addition, the study will compare sensitivities and specificities of the included RATs as well as RT-PCR on clinical samples obtained from the deep oropharynx, the anterior nasal cavity, saliva, the deep nasopharynx, and expired air to RT-PCR on deep oropharyngeal samples. In the prospective part of the study, 200 individuals found SARS-CoV-2 positive and 200 individuals found SARS-CoV-2 negative by routine RT-PCR testing will be retested with each RAT, applying RT-PCR as the reference method. In the retrospective part of the study, 304 deep oropharyngeal cavity swabs divided into 4 groups based on RT-PCR quantification cycle (Cq) levels will be tested with each RAT. The results will be reported in several papers with different aims. The first paper will report retrospective (analytical sensitivity, overall and stratified into different Cq range groups) and prospective (clinical sensitivity) data for RATs, with RT-PCR as the reference method. The second paper will report results for RAT based on anatomical sampling location. The third paper will compare different anatomical sampling locations by RT-PCR testing. The fourth paper will focus on RATs that rely on central laboratory testing. Tests from 4 different manufacturers will be compared for analytical performance data on retrospective deep oropharyngeal swab samples. The fifth paper will report the results of 4 RATs applied both as professional use and as self-tests. The last paper will report the results from 2 breath tests in the study. A comparison of sensitivity and specificity between RATs will be conducted using the McNemar test for paired samples and the chi-squared test for unpaired samples. Comparison of the positive predictive value (PPV) and negative predictive value (NPV) between RATs will be performed by the bootstrap test, and 95% CIs for sensitivity, specificity, PPV, and NPV will be calculated as bootstrap CIs. The study will compare the sensitivities of a large number of RATs for SARS-CoV-2 to with those of RT-PCR and will address whether lateral flow-based RATs differ significantly from laboratory-based RATs. The anatomical test locations for both RATs and RT-PCR will also be compared. ClinicalTrials.gov NCT04913116; https://clinicaltrials.gov/ct2/show/NCT04913116. DERR1-10.2196/35706.


Membrane-bound phospholipid desaturases.
This review covers studies on membrane-bound phospholipid desaturases in yeast and rat liver carried out in this laboratory. In yeast the desaturase system was shown to effect the direct desaturation of dioleoyl-lecithin to dilinoleoyl-lecithin. In rat liver the desaturase was capable of converting 2-eicosatrienoyl-lecithin to 2-arachidonoyl-lecithin. Both systems required reduced pyridine nucleotides, O2 and cytochrome b5. Eicosatrienoyl-lecithin desaturase along with eicosatrienoyl-CoA desaturase of rat liver microsomes was solubilized with detergents and purified 7-8-fold from the microsomal pellets. Both activities were reconstituted in the presence of deoxycholate on addition of the other components of the cytochrome b5-electron transport chain (cytochrome b5 and NADH-cytochrome b5 reductase) to the solubilized desaturase; addition of lecithin further stimulated the activities. The demonstration of desaturation of eicosatrienoyl-lecithin by a solubilized and partially purified desaturase provides strong evidence for the direct desaturation of the lecithin substrate without prior conversion to the acyl-CoA thiolester.


Relationship between smoking and postoperative complications of cervical spine surgery: a systematic review and meta-analysis.
To determine whether smoking has adverse effects on postoperative complications following spine cervical surgery (PROSPERO 2021: CRD42021269648). We searched PubMed, Embase, Cochrane Library, and Web of Science through 13 July 2021 for cohort and case-control studies that investigated the effect of smoking on postoperative complications after cervical spine surgery. Two researchers independently screened the studies and extracted data according to the selection criteria. The meta-analysis included 43 studies, including 27 case-control studies and 16 cohort studies, with 10,020 patients. Pooled estimates showed that smoking was associated with overall postoperative complications (effect estimate [ES] = 1.99, 95% confidence interval [CI]: 1.62-2.44, p < 0.0001), respiratory complications (ES = 2.70, 95% CI: 1.62-4.49, p < 0.0001), reoperation (ES = 2.06, 95% CI: 1.50-2.81, p < 0.0001), dysphagia (ES = 1.49, 95% CI: 1.06-2.10, p = 0.022), wound infection (ES = 3.21, 95% CI: 1.62-6.36, p = 0.001), and axial neck pain (ES = 1.98, 95% CI: 1.25-3.12, p = 0.003). There were no significant differences between the smoking and nonsmoking groups in terms of fusion (ES = 0.97, 95% CI: 0.94-1.00, p = 0.0097), operation time (weighted mean difference [WMD] = 0.08, 95% CI: -5.54 to 5.71, p = 0.977), estimated blood loss (WMD = -5.31, 95% CI: -148.83 to 139.22, p = 0.943), length of hospital stay (WMD = 1.01, 95% CI: -2.17 to 4.20, p = 0.534), Visual Analog Scale-neck pain score (WMD = -0.19, 95% CI: -1.19 to 0.81, p = 0.707), Visual Analog Scale-arm pain score (WMD = -0.50, 95% CI: -1.53 to 0.53, p = 0.343), Neck Disability Index score (WMD = 11.46, 95% CI: -3.83 to 26.76, p = 0.142), or Japanese Orthopedic Association Scores (WMD = -1.75, 95% CI: -5.27 to 1.78, p = 0.332). Compared with nonsmokers, smokers seem to be more significantly associated with overall complications, respiratory complications, reoperation, longer hospital stay, dysphagia, wound infection and axial neck pain after cervical spine surgery. It is essential to provide timely smoking cessation advice and explanation to patients before elective cervical spine surgery.


Pharmacokinetics of tacrolimus converted from twice-daily formulation to once-daily formulation in Chinese stable liver transplant recipients.
To evaluate the pharmacokinetics of tacrolimus in Chinese stable liver transplant recipients converted from immediate release (IR) tacrolimus-based immunosuppression to modified release (MR) tacrolimus-based immunosuppression. Open-label, multi-center study with a one-way conversion design was conducted. Eighty-three stable liver recipients (6-24 months post-transplant) with normal renal and stable hepatic function were converted from IR tacrolimus twice-daily treatment to MR tacrolimus once-daily treatment on a 1:1 (mg: mg) total daily dose basis. Twenty-four hour pharmacokinetic studies were carried out on d 0 (pre-conversion), d 1, and d 84 (post-conversion). The area under the blood concentration-time curve of MR tacrolimus from 0 to 24 h (AUC(0-24)) on d 1 was comparable to that of IR tacrolimus on d 0, with a 90% confidence interval (CI) for MR/IR tacrolimus of 92%-97%. The AUC(0-24) value for MR tacrolimus on d 84 with the daily dose increased by 14% was approximately 17% lower than that for IR tacrolimus. The 90% CI was 77%-90%, outside the bioequivalence range of 80%-125%. There was a good correlation between AUC(0-24) and concentration at 24 h (C(24)) for IR tacrolimus (d 0, r=0.930) and MR tacrolimus (d 1, r=0.936; d 84, r=0.903). The exposure to tacrolimus when administered MR tacrolimus once daily is not equivalent to that for IR tacrolimus twice daily after an 84-day conversion in Chinese stable liver transplant recipients. The dose should be adjusted on the basis of trough levels. The therapeutic drug monitoring for patients treated with IR tacrolimus is considered to be applicable to MR tacrolimus.


Enzymatic decolorization of melanin by lignin peroxidase from Phanerochaete chrysosporium.
Skin darkening results as a consequence of the accumulation of skin pigment melanin. To combat this, the amplitude of skin lightening agents are commercially available, most of which inhibit melanin synthesis. Decolorization of melanin is an alternative method of skin lightening. In this study, we show that lignin peroxidase (LiP), an extracellular enzyme purified from Phanerochaete chrysosporium NK-1 isolated from a forest soil can effectively degrade and decolorize melanin in vitro. Decolorization conditions including pH, temperature, incubation time, enzyme concentration, and mediator addition were investigated to optimize the reaction conditions. The results indicate that pH 3, 40 °C, 15 IU/ml, and 10 h incubation were the optimal conditions for the decolorization of the melanin. The use of the mediator, veratryl alcohol was also found effective to enhance the efficacy of the melanin decolonization, with up to 92% decolorization. The scanning electron microscopy results showed void spaces on the treated melanin granules as compared to the untreated sample, indicating the degradation of melanin. Changes in the fingerprint region of the melanin were observed. Between wavenumbers 1500-500 cm-1, for example, the presence of new peaks in the treated melanin at 1513, 1464, and 1139 cm-1 CH2, CH3 bend and C-O-C stretch represented structural changes. A new peak at 2144 cm-1 (alkynyl C≡C stretch) was also detected in the decolorized melanin. The cytotoxicity study has shown that the treated melanin and LiP have low cytotoxic effects; however, the mediator of veratryl alcohol could result in high mortality which suggests that its use should be meticulously tested in formulating health and skincare products. The findings of the study suggest that LiP produced by Phanerochaete chrysosporium has the potential to be used in the medical and cosmetic industries, particularly for the development of biobased cosmetic whitening agents.


Cochlear Implantation in a Patient with Failed Renal Transplant: A Case Report.
Cochlear implantation has become a standard tool of management of severe to profound hearing loss. Cochlear implantation in patients with chronic renal failure who are on hemodialysis are at greater risk of complications intraoperatively and postoperatively. Very few cases of cochlear implantation have been reported in the English literature so far following renal transplantation. Herein we report a case of cochlear implantation in a 37 year old lady with post renal transplant failure who is on maintenance hemodialysis.


Impacts of oxidative stress on acetylcholinesterase transcription, and activity in embryos of zebrafish (Danio rerio) following Chlorpyrifos exposure.
Organophosphate pesticides cause irreversible inhibition of AChE which leads to neuronal overstimulation and death. Thus, dogma indicates that the target of OP pesticides is AChE, but many authors postulate that these compounds also disturb cellular redox processes, and change the activities of antioxidant enzymes. Interestingly, it has also been reported that oxidative stress plays also a role in the regulation and activity of AChE. The aims of this study were to determine the effects of the antioxidant, vitamin C (VC), the oxidant, t-butyl hydroperoxide (tBOOH) and the organophosphate Chlorpyrifos (CPF), on AChE gene transcription and activity in zebrafish embryos after 72h exposure. In addition, oxidative stress was evaluated by measuring antioxidant enzymes activities and transcription, and quantification of total glutathione. Apical effects on the development of zebrafish embryos were also measured. With the exception of AChE inhibition and enhanced gene expression, limited effects of CPF on oxidative stress and apical endpoints were found at this developmental stage. Addition of VC had little effect on oxidative stress or AChE, but increased pericardial area and heartbeat rate through an unknown mechanism. TBOOH diminished AChE gene expression and activity, and caused oxidative stress when administered alone. However, in combination with CPF, only reductions in AChE activity were observed with no significant changes in oxidative stress suggesting the adverse apical endpoints in the embryos may have been due to AChE inhibition by CPF rather than oxidative stress. These results give additional evidence to support the role of prooxidants in AChE activity and expression.


Molecular characterization of a Penicillium chrysogenum exo-rhamnogalacturonan lyase that is structurally distinct from other polysaccharide lyase family proteins.
We previously described an endo-acting rhamnogalacturonan (RG) lyase, termed PcRGL4A, of Penicillium chrysogenum 31B. Here, we describe a second RG lyase, called PcRGLX. We determined the cDNA sequence of the Pcrglx gene, which encodes PcRGLX. Based on analyses using a BLAST search and a conserved domain search, PcRGLX was found to be structurally distinct from known RG lyases and might belong to a new polysaccharide lyase family together with uncharacterized fungal proteins of Nectria haematococca, Aspergillus oryzae, and Fusarium oxysporum. The Pcrglx cDNA gene product (rPcRGLX) expressed in Escherichia coli demonstrated specific activity against RG but not against homogalacturonan. Divalent cations were not essential for the enzymatic activity of rPcRGLX. rPcRGLX mainly released unsaturated galacturonosyl rhamnose (ΔGR) from RG backbones used as the substrate from the initial stage of the reaction, indicating that the enzyme can be classified as an exo-acting RG lyase (EC 18.104.22.168). This is the first report of an RG lyase with this mode of action in Eukaryota. rPcRGLX acted synergistically with PcRGL4A to degrade soybean RG and released ΔGR. This ΔGR was partially decorated with galactose (Gal) residues, indicating that rPcRGLX preferred oligomeric RGs to polymeric RGs, that the enzyme did not require Gal decoration of RG backbones for degradation, and that the enzyme bypassed the Gal side chains of RG backbones. These characteristics of rPcRGLX might be useful in the determination of complex structures of pectins.


Clinicopathological Analysis of Medullary Ray Injury in 1-Year Protocol Paediatric Renal Allograft Biopsies.
Medullary ray injury was recently reported in renal transplant biopsies. This study was performed to clarify the clinicopathological features of medullary ray injury in paediatric living renal transplant recipients. Paediatric recipients who completed a 5-year follow-up after living renal transplantation were enroled. We evaluated the clinical and pathological parameters of the presence or absence of medullary ray injury in their 1-year protocol biopsies. Of 48 1-year protocol biopsies, 18 (37.5%) showed histological evidence of medullary ray injury. The 48 paediatric recipients were classified as those with medullary ray injury (n = 18; MRI-1Y [+] group) and those without medullary ray injury (n = 30; MRI-1Y [-] group) in the 1-year protocol biopsies. The prevalence of histological evidence of calcineurin inhibitor (CNI) nephrotoxicity, chronic obstruction or reflux nephropathy, and imaging findings of vesicoureteral reflux was 66.7, 22.2, and 7.7% in the MRI-1Y (+) group and 33.3, 13.3, and 15.4% in the MRI-1Y (-) group, respectively. Only the prevalence of CNI nephrotoxicity was significantly different between the 2 groups. There was no significant difference in the mean estimated glomerular filtration rate at 1, 3, or 5 years after transplantation between the 2 groups. In total, 37.5% of 1-year protocol biopsies showed histological evidence of medullary ray injury. This finding suggests that CNI nephrotoxicity might be the main contributor to medullary ray injury in 1-year protocol biopsies. The presence of medullary ray injury had little influence on renal function, at least during the first 5 years after transplantation.


[Effect of indicator location on the psychophysiological characteristics of combined activities].
Investigation was carried out to estimate how efficiently can combined tasks of visual measurement and sensomotor reaction of choice be performed against tracking the sinusoidal signal at different sighting angles between their displays and different priority. It was found that, with a change in the sighting angle between the displays from 0 to 60 degrees, the time and number of tracking errors continuously increased; the probability of erroneous replies grew with an increase in the sighting angle to 30 degrees, remained essentially stable at angles of 30 and 45 degrees and decreased at 60 degrees. Combined performance of two equally important problems in case of an increase in the sighting angle between displays (from 30 to 45 degrees) was followed by a change in the structure of data acquisition.


Neural mechanisms supporting maladaptive food choices in anorexia nervosa.
People routinely make poor choices, despite knowledge of negative consequences. The authors found that individuals with anorexia nervosa, who make maladaptive food choices to the point of starvation, engaged the dorsal striatum more than healthy controls when making choices about what to eat, and that activity in fronto-striatal circuits was correlated with their actual food consumption in a meal the next day.


Fibronectin remains in the cytoskeletal preparations of cultured human fibroblasts.
Cytoskeleton models were produced by treating cultured human embryonal fibroblasts with Triton X-100 and actomyosin dissociating buffers. Morphological studies indicated that in addition to nuclear residues and intermediate filaments, both plasma membrane remnants and substratum-associated, pericellular material remained on the culture substratum. By immunochemical analysis the extracellular material was identified as fibronectin. The results suggest that fibronectin is associated with the nucleus-anchoring cytoskeleton of cultured human fibroblasts.


Methylene Blue Administration for Distributive Shock States in Critically Ill Children.
Methylene blue (MB), an inhibitor of nitric oxide synthesis and its effects is a potentially effective treatment against distributive shock states such as septic shock and vasoplegic syndrome. MB has been shown to alleviate vasoplegia and promote an increase in blood pressure. It may reduce mortality. However, in the pediatric population, there are few case reports and only one controlled study on administration of MB use for vasoplegia, sepsis, or shock in general. To summarize the experience of administering MB for vasoplegic shock in a tertiary care pediatric intensive care unit. A retrospective chart review of seven pediatric cases treated with MB for vasoplegic shock was conducted. MB was administered as a bolus followed by continuous infusion. The authors measured blood pressure, vasopressor, and inotropic support. Patient outcome was monitored. The authors observed a favorable hemodynamic response with an increase in blood pressure and a reduction in vasopressor and inotropic support needed following MB administration in six patients. No side effects were observed. Three patients eventually died one to two days later, secondary to their underlying disease. This case series adds to the small body of evidence in the pediatric population supporting the use of MB for distributive shock states and emphasizes the need for larger, randomized trials evaluating its role in vasoplegic shock treatment.


Reproducibility and diagnostic sensitivity of ultrasonometry of the phalanges to assess osteoporosis.
The present study was designed to assess the reproducibility and the diagnostic sensitivity of the amplitude-dependent speed of sound (SoS) at the distal metaphysis of the proximal phalanges. Fourteen presumably healthy volunteers were repeatedly measured every 6 weeks for approximately 6 months in order to assess the reproducibility of the SoS of the phalanges. We recruited 91 post-menopausal women, aged 55-75 years, who were divided in three groups according to their lumbar bone mineral density (BMD) and the existence of prevalent vertebral fractures. The objective was to evaluate the diagnostic sensitivity of SoS measurements. We used DBM Sonic 1200 equipment, and assessed the velocity at which US cross the phalanx in a lateral-medial direction. In post-menopausal women, BMD was measured by dual energy X-ray absorptiometry (DXA) at the level of the lumbar spine, the total zone of the non-dominant hip and the femoral neck zone of the non-dominant hip. The precision of the SoS measurements was 0.71+/-0.05% (mean+/-S.E.M) whereas the reproducibility was 0.95+/-0.06%. Subjects with low BMD or prevalent fractures had significantly lower values of SoS (P < 0.001) than the controls. ROC curve analysis applied to the study population confirmed that SoS was able to discriminate between the controls and osteoporotic subjects (area under the ROC curves were 0.82 (low bone mineral density) and 0.85 (prevalent fractures), respectively). Hip BMD was found to be the most significant variable when comparing the controls and the low density patients by stepwise discrimination and SoS significantly improved the discrimination between the groups when added to the hip BMD. The hip BMD was again the most discriminant variable when applying the same techniques to controls and patients with prevalent fractures, followed by SoS and lumbar BMD. A cut-off value of 1881 m/s is defined for SoS by logistic discrimination and likelihood ratio function. With this value, the sensitivity and the specificity for SoS used in the diagnosis of established osteoporosis were, 81.5% and 79.3%, respectively. Sensitivity and specificity were significantly improved when combining ultrasonometry and densitometry. Measurement of ultrasound velocity at the phalanges appears to be a precise and reproducible technique. SoS discriminates between normal post-menopausal women and patients with either low lumbar BMD or prevalent fractures to the same extent as BMD measurements.


3,4-Dichlorophenoxyacetate interleaved into anionic clay for controlled release formulation of a new environmentally friendly agrochemical.
A new layered organic-inorganic nanohybrid material, zinc-aluminum-3,4-dicholorophenoxyacetate (N3,4-D) in which an agrochemical, 3,4-dichlorophenoxyacetic acid (3,4-D), is intercalated into zinc-aluminum-layered double hydroxide (ZAL), was synthesized by coprecipitation method. A well-ordered nanomaterial was formed with a percentage loading of 53.5% (w/w). Due to the inclusion of 3,4-D, basal spacing expanded from 8.9 Å in ZAL to 18.7 Å in N3,4-D. The Fourier transform infrared study shows that the absorption bands of the resulting nanohybrid composed of both the 3,4-D and ZAL further confirmed the intercalation episode. Thermal analysis shows that ZAL host enhances the thermal stability of 3,4-D. Controlled-release experiment shows that the release of 3,4-D in the aqueous media is in the order of phosphate > carbonate > sulfate > chloride. These studies demonstrate the successful intercalation of the 3,4-D and its controlled release property in various aqueous media.


Associations between accessibility to health care service, social support, and Korean Americans' mental health status amid the COVID-19 pandemic.
While previous studies have examined the relationships between social support and health care accessibility among ethnic minority populations, studies on Korean Americans remain scarce. Therefore, this study aims to assess the relationship between Korean Americans' mental health, accessibility to health care, and how they perceive the level of social support during the COVID-19 pandemic. We distributed online surveys to Korean Americans from May 24, 2020, to June 14, 2020, generating 790 responses from participants residing in 42 states. Binary Logistic and Ordinary Least Square regression analyses revealed that poor mental health was associated with language barriers inhibiting Korean Americans' access to COVID-19-related information. Their perceived social support from family members and close friends was positively associated with mental health. Our findings recommend that equipping community health care services with translators or interpreters is necessary. Additionally, health practitioners and staff should be trained to utilize telehealth tools to effectively treat individuals with mental health problems. American policymakers and health care professionals need to understand and address the unique hardships Korean Americans experience amid COVID-19.


The dietary inflammatory index is directly associated with polycystic ovary syndrome: A case-control study.
The association between diet and polycystic ovary syndrome (PCOS) might be mediated by the inflammatory properties of the diet. The study aimed to investigate the relationships between the dietary inflammatory index (DII) with odds of PCOS among the adult population. In the hospital-based case-control study, 203 patients with PCOS and 291 non-PCOS controls were enroled. DII was calculated via a validated 147-item quantitative food frequency questionnaire (FFQ). Thirty-six macro- and micronutrients were extracted from FFQ and used to calculate DII. Employing a case-control design, odds ratios (ORs) and 95% confidence intervals (CIs) were obtained, with a dose-response effect confirmed by the test for trend (p for trend). The mean ± SD age and body mass index (BMI) of the study participants were 29.67 ± 5.92 years and 24.51 ± 4.71 kg/m2 , respectively. Compared with controls subjects, PCOS patients had significantly higher weight, BMI, and waist circumferences, but had lower physical activity. PCOS subjects had higher intakes of carbohydrate, cholesterol, and refined grains, but lower intakes of polyunsaturated fatty acids, fibre, vitamin B12 , vitamin D, and dairy as compared to controls. Compared with participants in the lowest quartile of DII, those in the highest quartile had a significantly higher OR for PCOS after further adjustment for potential confounders (OR = 1.75, 95% CI: 0.95-3.22). Our data suggest that high DII was associated with an increased odds of PCOS diagnosis. Prospective dietary intervention studies and observational prospective cohorts are required to confirm these findings.


Hemodynamic collapse during pulmonary embolectomy due to loss of venous return from acute occlusion of the cardiopulmonary venous cannula with thromboembolus.
We report a case of hemodynamic collapse during pulmonary embolectomy with cardiopulmonary bypass. The hemodynamic collapse was due to complete loss of venous return due to thromboembolic occlusion of the atrial cannula. The diagnosis was made during focused intraoperative transesophageal echocardiography.


[Clinical study on effect of local administration of amikacin for complicated cystitis accompanied by residual urine].
Amikacin 600 mg was administered into the bladder to treat complicated cystitis with benign prostatic hyperplasia or neurogenic bladder after removing residual urine in the bladder in 18 patients. The overall effective rate was 88.9% (excellent in 15 cases, moderate in 1 case, poor in 1 case). The period of effectiveness was from 1 to 8 weeks after administration of Amikacin. No side effects were seen.


Prostaglandin E2 metabolism in rat brain: Role of the blood-brain interfaces.
Prostaglandin E2 (PGE2) is involved in the regulation of synaptic activity and plasticity, and in brain maturation. It is also an important mediator of the central response to inflammatory challenges. The aim of this study was to evaluate the ability of the tissues forming the blood-brain interfaces to act as signal termination sites for PGE2 by metabolic inactivation. The specific activity of 15-hydroxyprostaglandin dehydrogenase was measured in homogenates of microvessels, choroid plexuses and cerebral cortex isolated from postnatal and adult rat brain, and compared to the activity measured in peripheral organs which are established signal termination sites for prostaglandins. PGE2 metabolites produced ex vivo by choroid plexuses were identified and quantified by HPLC coupled to radiochemical detection. The data confirmed the absence of metabolic activity in brain parenchyma, and showed that no detectable activity was associated with brain microvessels forming the blood-brain barrier. By contrast, 15-hydroxyprostaglandin dehydrogenase activity was measured in both fourth and lateral ventricle choroid plexuses from 2-day-old rats, albeit at a lower level than in lung or kidney. The activity was barely detectable in adult choroidal tissue. Metabolic profiles indicated that isolated choroid plexus has the ability to metabolize PGE2, mainly into 13,14-dihydro-15-keto-PGE2. In short-term incubations, this metabolite distributed in the tissue rather than in the external medium, suggesting its release in the choroidal stroma. The rat choroidal tissue has a significant ability to metabolize PGE2 during early postnatal life. This metabolic activity may participate in signal termination of centrally released PGE2 in the brain, or function as an enzymatic barrier acting to maintain PGE2 homeostasis in CSF during the critical early postnatal period of brain development.


Ingredients contribute to variation in production of reactive oxygen species by areca quid.
Areca quid (AQ) chewing has been implicated an independent risk factor for the development of oral cancer. Taiwanese areca quid (AQ) refers to a combination of areca nut (AN), lime, and inflorescence of Piper betle Linn. (IPB) or Piper betle leaf (PBL). Studies of AQ in other countries reported that AN extract combined with lime generates reactive oxygen species (ROS), such as hydroxyl radical (HO.), known to be a contributing factor in oral mucosa damage. To determine whether HO. is formed in the oral cavity during AQ chewing, the formation of meta-tyrosine (m-Tyr) and ortho-tyrosine (o-Tyr) from l-phenylalanine (Phe) was confirmed. It was demonstrated that combined aqueous extracts of AN, lime, metal ions (such as Cu2+ and Fe2+), and IPB or PBL produced HO.. Thus, the yield of HO. significantly increases when higher amounts of IPB or lime are added and also when Cu2+ and Fe2+ are increased. Further, the omission of any one of these ingredients significantly reduces the formation of HO.. Our results found that chewing AQ with IPB generated significantly higher HO. than chewing AQ with PBL, and may result in greater oxidative damage to the surrounding oral mucosa.


The mechanism of alkene addition to a nickel bis(dithiolene) complex: the role of the reduced metal complex.
The binding of an alkene by Ni(tfd)(2) [tfd = S(2)C(2)(CF(3))(2)] is one of the most intriguing ligand-based reactions. In the presence of the anionic, reduced metal complex, the primary product is an interligand adduct, while in the absence of the anion, dihydrodithiins and metal complex decomposition products are preferred. New kinetic (global analysis) and computational (DFT) data explain the crucial role of the anion in suppressing decomposition and catalyzing the formation of the interligand product through a dimetallic complex that appears to catalyze alkene addition across the Ni-S bond, leading to a lower barrier for the interligand adduct.


Effects of long-term exposure to PM2.5 on years of life lost and expected life remaining in Ahvaz city, Iran (2008-2017).
Ambient air pollution is one of the most significant environmental problems, and many individuals around the world die each year prematurely from diseases caused by this type of pollution. PM2.5 can transpire deep to the lungs and induce some dangerous health effects in humans. In this study, the health effects of long-term PM2.5 were estimated on expected life remaining (ELR) and years of life lost (YLL) indices in Ahvaz city during the years 2008-2017 using the AirQ+ software developed by WHO. Values obtained from the PM2.5 averaging, ELR, and YLL data were processed for the whole population in the age range of 0-64 and over 64. These values were entered into AirQ+ software. The mean annual concentration of PM2.5 was highly variable, with the highest concentration being 70.72 μg/m3 in 2010 and the lowest 41.97 μg/m3 in 2014. In all studied years, the concentration of PM2.5 with the variations between 4.2 to 7.07 times was higher than the WHO standard (10 μg/m3). Ahvaz city also did not experience any clean day during the 10-year period, and in 2010, there were 47 very unhealthy days and 27 dangerous days, i.e., the highest number of very unhealthy and dangerous days during the period. The results estimated that the highest and lowest YLL in the next 10 years for all ages groups would be 137,760.49 (2010) and 5035.52 (2014), respectively. Also, the ELR index was lower than the Iranian standard and EPA which was significantly correlated with the concentration of PM2.5.


Twin pregnancy: routine use of ultrasound examinations in the prenatal diagnosis of intrauterine growth retardation and discordant growth.
A prospective study was undertaken in 42 normal twin pregnancies to determine the value of routine ultrasound evaluation in the prenatal diagnosis of intrauterine growth retardation (IUGR) and intra-pair growth discordancy in twin gestations. Use of multiple sonographic parameters significantly improved diagnostic accuracy when compared with the use of single parameters, such as biparietal diameter (BPD) alone in the prepartum diagnosis of these two entities.


Human thermal comfort conditions and urban planning in hot-humid climates-The case of Cuba.
Climate regional characteristics, urban environmental conditions, and outdoors thermal comfort requirements of residents are important for urban planning. Basic studies of urban microclimate can provide information and useful resources to predict and improve thermal conditions in hot-humid climatic regions. The paper analyzes the thermal bioclimate and its influence as urban design factor in Cuba, using Physiologically Equivalent Temperature (PET). Simulations of wind speed variations and shade conditions were performed to quantify changes in thermal bioclimate due to possible modifications in urban morphology. Climate data from Havana, Camagüey, and Santiago of Cuba for the period 2001 to 2012 were used to calculate PET with the RayMan model. The results show that changes in meteorological parameters influence the urban microclimate, and consequently modify the thermal conditions in outdoors spaces. Shade is the predominant strategy to improve urban microclimate with more significant benefits in terms of PET higher than 30 °C. For climatic regions such as the analyzed ones, human thermal comfort can be improved by a wind speed modification for thresholds of PET above 30 °C, and by a wind speed decreases in conditions below 26 °C. The improvement of human thermal conditions is crucial for urban sustainability. On this regards, our study is a contribution for urban designers, due to the possibility of taking advantage of results for improving microclimatic conditions based on urban forms. The results may enable urban planners to create spaces that people prefer to visit, and also are usable in the reconfiguration of cities.


An integrated Java tool for generating amino acid sequence alignments with mapped secondary structure elements.
The mapping of secondary structure elements onto amino acid sequences enhances the quality of alignments frequently used in phylogenetic, genomic and transcriptomic studies, as well as in molecular modelling. Here, we report recent updates to the Java application SBAL, an integrated tool to generate, edit, visualise and analyse secondary structure-based sequence alignments. The main goal of the software is to streamline the work flow in generation of structure-based alignments, and we have thus implemented the option to import and visualise sequence and structure information directly from any PDB file. The new feature is achieved by a Java application named ASSP which follows the original framework of the well-established dictionary of protein secondary structure by Kabsch and Sander. ASSP is also available as a stand-alone application. Other major additions to SBAL include the calculation of distance matrices, peptide properties, as well as detailed on-line tutorials for typical applications.


Fludarabine-based reduced intensity regimen for matched related donor hematopoietic stem cell transplantation in acquired severe aplastic anemia.
Different conditioning regimens have been evaluated in matched-related donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acquired severe aplastic anemia (SAA) with varying results. In this manuscript, we report our experience with fludarabine (120mg/m2), very low dose cyclophosphamide (1200mg/m2) and antithymocyte globulin (7.5mg/kg). Low dose total body irradiation (2Gy) was added to the conditioning regimen for patients older than 15 years. Nineteen patients (median age 23years) underwent transplant between 2008 and 2015. The majority (89%) were younger than 40 years. Stem cell source was BM (n=11) or PBSC (n=8). GvHD prophylaxis consisted of cyclosporine and either a short course of methotrexate (n=9) or mycophenolate mofetil (n=10). Eighteen (94.7%) patients achieved sustained engraftment. The median times to neutrophil and platelet engraftments were 19 (range: 14-34) and 17.1 (range: 12-25) days, respectively. The day-30 cumulative incidence of neutrophil and platelet engraftment was 89.4% and 94.7%, respectively. No secondary graft rejection was observed. The 1-year cumulative incidence of aGvHD (grade II-IV) and cGvHD was 11.7% and 0%, respectively. The 2-year GvHD-free survival rate was 78.6% (95% CI: 52.5-91.4%). Fludarabine-based reduced intensity regimen for MRD allo-HSCT in SAA compares favorably to other available regimens. This regimen deserves further investigations with larger cohort of patients.


Targeting of liposomes to human keratinocytes through adhesive peptides from immunoglobulin domains in the presence of IFN-gamma.
T-cell adhesion is often dictated by the presence of intercellular adhesion molecule-1 (ICAM-1) on the target cell surface. Reconstitution of P(0) protein into liposomes increases adhesion to melanoma cells expressing ICAM-1. In our study, the effect of peptides derived from P(0) protein and leukocyte function associated-antigen 1 (LFA-1) on IFN-gamma-stimulated human keratinocytes was investigated. Covalently linked P(0)-peptide-1, from the Ig-like domain, increased specific liposome binding to IFN-gamma-stimulated keratinocytes in a dose-dependent manner. C-terminal-derived P(0)-peptide-3 increased liposome binding nonspecifically. LFA-1 and RGD peptides had no apparent effect. P(0)-peptide-1 is thus a potential targeting ligand for liposomal drug delivery to ICAM-1 expressing keratinocytes in inflammatory dermatoses.


An electron microscopic histochemical investigation of the localization of creatine phosphokinase in heart cells.
The results of an electron microscopic histochemical investigation performed in the current study indicate that in heart cells creatine phosphokinase is localized: (1) inside mitochondria mainly on the cristae membranes, (2) on the membrane of the sarcoplasmic reticulum, (3) on myofibrils (and in cytoplasm), (4) on the plasma membrane of the cells, (5) on the membrane of the cell nuclei.


Influence of genetic variations on levels of inflammatory markers of healthy subjects at baseline and one week after clopidogrel therapy; results of a preliminary study.
We aimed to assess the association between the most common polymorphisms of cytochrome P450 (CYP) epoxygenases on the plasma levels of inflammatory markers in a population of healthy subjects. We also sought to determine whether CYP2C19 2 polymorphism is associated with the anti-inflammatory response to clopidogrel. In a population of 49 healthy young males, the baseline plasma levels of inflammatory markers including C-reactive protein, haptoglobin, orosomucoid acid, CD-40 were compared in carriers vs. non-carriers of the most frequent CYP epoxygenase polymorphisms: CYP2C9 2, CYP2C9 3, CYP2C19 2, CYP2C8 2 and CYP2J2 7. Also, the variation of inflammatory markers from baseline to 7 days after administration of 75 mg per day of clopidogrel were compared in carriers vs. non-carriers of CYP2C19 allele and also in responders vs. hypo-responders to clopidogrel, determined by platelet reactivity tests. There was no significant association between epoxygenase polymorphisms and the baseline levels of inflammatory markers. Likewise, CYP2C19 allele was not associated with anti-inflammatory response to clopidogrel. Our findings did not support the notion that the genetic variations of CYP epoxygenases are associated with the level of inflammatory markers. Moreover, our results did not support the hypothesis that CYP2C19 2 polymorphism is associated with the variability in response to the anti-inflammatory properties of clopidogrel.


Programmable DNA Nanosystem for Molecular Interrogation.
We describe a self-assembling DNA-based nanosystem for interrogating molecular interactions. The nanosystem contains a rigid supporting dumbbell-shaped frame, a cylindrical central core, and a mobile ring that is coaxial with the core. Motion of the ring is influenced by several control elements whose force-generating capability is based on the transition of single-stranded DNA to double-stranded DNA. These forces can be directed to act in opposition to adhesive forces between the ring and the frame thereby providing a mechanism for molecular detection and interrogation at the ring-frame interface. As proof of principle we use this system to evaluate base stacking adhesion and demonstrate detection of a soluble nucleic acid viral genome mimic.


Utilization of genomic signatures to direct use of primary chemotherapy.
The success of treatment of cancer patients depends on matching the most effective therapeutic regimen with the characteristics of the individual patient, balancing benefit against risk of adverse events. The primary challenge in achieving this goal is the heterogeneity of the disease, recognizing that breast, lung, colon and other cancers are not single diseases but rather an array of disorders with distinct molecular mechanisms. Genomic analyses, and in particular gene expression profiling, has been shown to have the capacity to dissect this heterogeneity and afford opportunities to match therapies with the characteristics of the individual patient's tumor. Here we review the success in developing gene expression signatures that have the capability of predicting response to various commonly used and newly developing cancer therapeutics. We further discuss the challenges and the opportunities in utilizing these tools in present-day clinical practice.


Life in heaps: a review of microbial responses to variable acidity in sulfide mineral bioleaching heaps for metal extraction.
Industrial heap leaching of low grade mineral sulfide ores is catalysed by the use of acidophilic microorganisms. These microorganisms obtain energy for growth from the oxidation of reduced inorganic or organic compounds, including soluble ferrous ion, reduced inorganic sulfur compounds (RISC) and acid-stable organic compounds. By-products of these oxidative processes, such as soluble ferric ion and sulfuric acid create favourable chemical conditions for leaching. This review is focused on the behaviour of common bioleaching microorganisms, their responses to changing pH in an industrial setting, and how both changes and microbial responses can impact the micro and macro environment.


EBV DNA increase in COVID-19 patients with impaired lymphocyte subpopulation count.
The immunologic profile and opportunistic viral DNA increase were monitored in Italian patients with COVID-19 in order to identify markers of disease severity. A total of 104 patients infected with SARS-CoV-2 were evaluated in the study. Of them, 42/104 (40.4%) were hospitalized in an intensive care unit (ICU) and 62/104(59.6%) in a sub-intensive care unit (SICU). Human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), Parvovirus B19 and Human Herpesvirus 6 virus reactivations were determined by real-time PCR, and lymphocyte subpopulation counts were determined by flow cytometry. Among opportunistic viruses, only EBV was consistently detected. EBV DNA was observed in 40/42 (95.2%) of the ICU patients and in 51/61 (83.6%) of the SICU patients. Comparing the two groups of patients, the EBV DNA median level among ICU patients was significantly higher than that observed in SICU patients. In parallel, a significant reduction of CD8 T cell and NK count in ICU patients as compared with SICU patients was observed (p<0.05). In contrast, B cell count was significantly increased in ICU patients (p=0.0172). A correlation between reduced CD8+ T cells and NK counts, EBV DNA levels and COVID-19 severity was observed. Other opportunistic viral infections were not observed. The relationship between EBV load and COVID-19 severity should be further evaluated in longitudinal studies.


Clinical evaluation of a fully automated and high-throughput molecular testing system for detection of influenza virus.
We investigated the performance of the cobas® 6800 system and cobas SARS-CoV-2 & Influenza A/B, a fully automated molecular testing system for influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This enabled an assay in a batch of 96 samples in approximately 3 h. An assay was performed using the cobas SARS-CoV-2 & Influenza A/B on the cobas 6800 system for samples collected in four facilities between November 2019 and March 2020 in our previous study. The results were compared with those obtained using the reference methods. Of the 127 samples analyzed, the cobas SARS-CoV-2 & Influenza A/B detected influenza A virus in 75 samples, of which 73 were positive using the reference methods. No false negative results were observed. The overall positive and negative percent agreement for influenza A virus detection were 100.0% and 96.3%, respectively. There were no positive results for the influenza B virus or SARS-CoV-2. The cobas 6800 system and cobas SARS-CoV-2 & Influenza A/B showed high accuracy for influenza A virus detection and can be useful for clinical laboratories, especially those that routinely assay many samples.


Definition of protocols for cryopreservation and three-dimensional in vitro culture of prepubertal goat testicular tissue after histomorphological, ultrastructural, and functional analysis.
This study aims to define the best method (slow freezing or vitrification) and fragment size (1, 5, or 9 mm³) for prepubertal goat testis cryopreservation, as well as to evaluate testicular morphological integrity after cryopreservation and in vitro culture (IVC). Initially (experiment I), 1, 5, or 9 mm³ testis fragments were cryopreserved by slow freezing using a Mr. Frosty container with 20% Dimethylsulfoxide (DMSO) or vitrified using the Ovarian Tissue Cryosystem (OTC) device, (Equilibration solution - ES: 10% DMSO and 10% ethylene glycol - EG; Vitrification solution - VS: 20% DMSO and 20% EG) and then subjected to morphological analysis, type I and III collagen quantification and gene expression (Oct4, C-kit, Bax, and Bcl-2). Subsequently, (experiment II), fresh or cryopreserved by slow freezing testis fragments were cultured in vitro and submitted to morphological analysis by scanning electron microscopy. The data from the experiment I revealed fewer morphological alterations in 1 and 5 mm³ fragments after vitrification and slow freezing, respectively. The percentage of type I collagen fibers in 5 and 9 mm³ frozen was higher than in fresh or vitrified fragments. For type III collagen, fresh or frozen fragments of 1 and 5 mm3 showed a higher percentage than fragments of 9 mm3. Gene expression for Oct4 and C-kit after slow freezing or vitrification in the 5 mm3 fragments was lower than that observed in the fresh fragments. The Bax:Bcl-2 ratio in the 1 and 9 mm³ fragments was lower than in the 5 mm³ fragments for fresh fragments or after freezing. In experiment II, fragments cultured in vitro, previously frozen or not, showed more morphological alterations than fresh or frozen fragments. We concluded that slow freezing of 5 mm³ fragments was the best protocol for cryopreserving prepubertal goat testis and although the results of IVC are encouraging, it still needs improvement to restore testicular function after cryopreservation.


Alteration of specific cytokine expression patterns in patients with breast cancer.
Systemic inflammation has been associated with aggressive tumor growth, invasion, and metastasis. Here we performed a comprehensive analysis of 26 kinds of inflammatory cytokine expression patterns among 185 patients with breast cancer and 54 healthy volunteers followed by chemometric analysis. We identified the specific cytokine expression patterns of breast cancer patients compared to healthy volunteers with (1) VEGF, IL-9, GM-CSF, IL-13, IL-4, and IFNγ, (2) IL-8, IL-10, IL-12, IL-5, IL-7, IL-1α, GCSF, IL-1β, and TNFα and (3) IL-2, Eotaxin, MIP1β, MIP1α, IL-17, and bFGF. Among the patients with breast cancer, we identified the specific cytokine signature of metastatic patients compared to non-metastatic patients. We also established a mathematical model for distinguishing patients with breast cancer from healthy volunteers and metastatic patients from non-metastatic patients. This cytokine network analysis could provide new insights into early intervention and effective therapeutic strategy for patients with breast cancer.


Outcomes associated with different surgical approaches to radical hysterectomy: A systematic review and network meta-analysis.
To evaluate the efficacy and safety of five different approaches to cervical cancer surgery. We conducted a systematic search for comparative studies on different radical hysterectomy types for cervical cancer in PubMed, Embase, the Cochrane Library, and Web of Science databases. All included observational studies used survival analyses to compare clinical outcomes of patients undergoing different radical hysterectomy types. All studies were assessed by the Newcastle-Ottawa Scale with scores of at least seven points. We extracted the relevant data and conducted a network meta-analysis to compare clinical outcomes among five surgical approaches. Thirty studies (n = 11 353) were included. Robotic surgery had the lowest blood loss volume and hospitalization duration; open surgery had the shortest operative time. Vaginal assisted laparoscopic surgery was associated with the highest number of resected lymph nodes and lowest rate of perioperative complications. Survival outcomes and tumor recurrence outcomes were similar among the approaches. The current approaches to cervical cancer surgery have comparable efficacies.


FMRFamide-like immunoreactivity in rat brain: development of a radioimmunoassay and its application in studies of distribution and chromatographic properties.
A radioimmunoassay is described for the molluscan neuropeptide, Phe-Met-Arg-Phe-NH2 (FMRFamide). The antibody used is C-terminal-specific and shows slight but significant (1-2%) cross-reactivity with chicken pancreatic polypeptide (APP). The assay has been used to identify in rat brain extracts a pair of molecules that may represent mammalian counterparts of FMRFamide. Their concentrations were highest in spinal cord and hypothalamus (greater than 10 pmol . g-1) and lowest in cerebellum and striatum (less than 3.5 pmol . g-1). The two immunoreactive peptides were separated on CM ion-exchange chromatography where they appeared to be less basic than FMRFamide. On Sephadex G50 gel filtration one eluted in a similar position of FMRFamide and the other slightly earlier suggesting it may be of higher molecular weight. The rat immunoreactive components do not correspond to previously described neuropeptides or hormones, and may be members of a new group of mammalian neuropeptides with transmitter or modulatory functions.


Incidence of hypertension in an ambulatory elderly population.
Investigations of the natural history of blood pressure have generally evaluated mean systolic and diastolic pressure changes. While information, this information is not directly applicable to clinical practice settings, in which patients are usually classified as normotensive or hypertensive. We measured the actual incidence of hypertension, using two different definitions, in an ambulatory elderly population of 2,584 individuals over an 8-year period. Using the less stringent blood pressure definition (systolic blood pressure greater than 140 mmHg and diastolic blood pressure greater than or equal to 90 mmHg), 884 (34.2%) participants were normotensive and 1,700 (65.8%) were hypertensive at an initial screening. The average annual incidence of hypertension over the subsequent eight years was 13.2%, and life tables demonstrated a gradual risk of developing hypertension. The development of hypertension was not associated with gender or age; while older age groups had a greater chance of developing hypertension than younger, the difference did not reach statistical significance.


A detailed look at the impacts of biofloc on immunological and hematological parameters and improving resistance to diseases.
The innate immunity of invertebrates serves as a critical trait that provides a valuable foundation for studying the common biological responses to environmental changes. With the exponential growth of the human population, the demand for protein has soared, leading to the intensification of aquaculture. Regrettably, this intensification has resulted in the overuse of antibiotics and chemotherapeutics, which have led to the emergence of resistant microbes or superbugs. In this regard, biofloc technology (BFT) emerges as a promising strategy for disease management in aquaculture. By harnessing the power of antibiotics, probiotics, and prebiotics, BFT offers a sustainable and eco-friendly approach that can help mitigate the negative impacts of harmful chemicals. By adopting this innovative technology, we can enhance the immunity and promote the health of aquatic organisms, thereby ensuring the long-term viability of the aquaculture industry. Using a proper carbon to nitrogen ratio, normally adding an external carbon source, BFT recycles waste in culture system with no water exchange. Heterotrophic bacteria grow along with other key microbes in the culture water. Heterotrophs play a major role in assimilating ammonia from feed and fecal waste, crucial pathway to form suspended microbial aggregates (known as 'biofloc'); while chemoautotrophs (e.g. nitrifying bacteria) oxidize ammonia into nitrite, and nitrite into nitrate promoting a healthy farming conditions. By using a highly aerated media and an organic substrates that contain carbon and nitrogen, protein-rich microbes are able to flocculate in culture water. Several types of microorganisms and their cell components have been studied and applied to aquatic animals as probiotics or immunostimulants (lipopolysaccharide, peptidoglycan, and 1-glucans) to enhance their innate immunity and antioxidant status, thereby enhancing their resistance to disease. In recent years, many studies have been conducted on the application of BFT for different farmed aquatic species and it has been observed as a promising method for the development of sustainable aquaculture, especially due to less use of water, increased productivity and biosecurity, but also an enhancement of the health status of several aquaculture species. This review analyses the immune status, antioxidant activity, blood and biochemical parameters, and level of resistance against pathogenic agents of aquatic animals farmed in BFT systems. This manuscript aims to gather and showcase the scientific evidences related to biofloc as a 'health promoter' in a unique document for the industry and academia.


An investigation into a cardiolipin acyl chain insertion site in cytochrome c.
Mitochondrial cytochrome c associates with the phosphoplipid cardiolipin (CL) through a combination of electrostatic and hydrophobic interactions. The latter occurs by insertion into cytochrome c of an acyl chain, resulting in the dissociation of the axial Met-80 heme-iron ligand. The resulting five coordinate cytochrome c/CL complex has peroxidatic properties leading to peroxidation of CL and dissociation of the complex. These events are considered to be pre-apoptotic and culminate with release of cytochrome c from the mitochondria into the cytoplasm. Two distinct surface regions on cytochrome c have been suggested to mediate CL acyl chain insertion and this study has probed one of these regions. We have constructed a series of alanine mutants aimed at disrupting a surface cleft formed between residues 67-71 and 82-85. The physicochemical properties, peroxidase activity, CL binding, and kinetics of carbon monoxide (CO) binding to the ferrous cytochrome c/CL complex have been assessed for the individual mutants. Our findings reveal that the majority of mutants are capable of binding CL in the same apparent stoichiometry as the wild-type protein, with the extent to which the Met-80 ligand is bound in the ferrous cytochrome c/CL complex being mutant specific at neutral pH. Mutation of the species conserved Arg-91 residue, that anchors the cleft, results in the greatest changes to physicochemical properties of the protein leading to a change in the CL binding ratio required to effect structural changes and to the ligand-exchange properties of the ferrous cytochrome c/CL complex.


Using multicolor perceptual markings as a rear-end crash risk mitigator: A field investigation.
Perceptual markings on roadways are prevailing countermeasures with substantial effectiveness for accident prevention, and a variety of alternatives and derivatives of them are developed to expect to receive an augmented performance of behavioral intervention and crash risk mitigation. However, the proper use of colors as a way of developing effective and innovative perceptual markings is seldomly recognized in-depth from the perspective of visual perceptual mechanism in behind. Given this, in this study, we introduced a kind of multicolor perceptual markings (MCPMs) pattern, i.e., one red marking follows one yellow marking ("1Y + 1R"), two red markings follow two yellow markings ("2Y + 2R"), and three red markings follow three yellow markings ("3Y + 3R"), and evaluated their effects on longitudinal and lateral driving behaviors and real-time safety benefits in car-following via a series of field investigation on a real-world expressway in China. The statistical analyses of the relative differences of speed (θv), distance headway (θd), time headway (θh), lateral movement (θp), and crash risk (ηmTTC and ηDRAC, developed from time-to-collision (TTC) and deceleration rate to avoid crash (DRAC)) suggest that, 1) the MCPMs could lead to substantial increases in car-following time and distance headways, and reduction in speed. The maximum time headway increase (0.61 s), speed reduction (1.42 m/s), and distance increase (3.6 m) were found in the condition of "1Y + 1R" compared with the baseline; 2) the MCPMs stabilized the lateral movement of vehicles on the lane at each observation section, and "1Y + 1R" yielded the best performance of lane-keeping; 3) the MCPMs yielded applaudable real-time safety benefits, which were believed to afford the drivers a better chance to accommodate their behaviors to a safer car-following status. The findings of this study suggest the MCPMs could be an especially applaudable form of perceptual markings, and could also be a critical reference of how to use colors in a better way for developing augmented perceptual markings.


Enhanced removal of tetrachloroethylene from aqueous solutions by biodegradation coupled with nZVI modified by layered double hydroxide.
Chlorinated volatile organic compounds, such as tetrachloroethylene (PCE), are the most commonly detected toxic contaminants in groundwater. In this study, the performance of PCE removal by a microbial consortium combined with nZVI modified by layered double hydroxide (nZVI-LDH) was evaluated. The enriched PCE-degrading consortium consisted of 44.49% Clostridium and other potential PCE degraders, and 0.5-2.5 mg/L PCE was completely biodegraded within 4 days. The characterization of nZVI-LDH indicated that LDH was coated on the surfaces of nZVI particles with an increased surface area. The PCE removal kinetics by nZVI-LDH was well described by a second-order model, and the removal rate constant of nZVI-LDH was 0.12 L h/mg, higher than that of native nZVI (0.02 L h/mg). Interestingly, the presence of Cu2+ improved the removal efficiency of PCE by nZVI-LDH, owing to its role as a catalyst or medium for charge transfer during reduction. Removal of PCE was enhanced by coupling the PCE-degrading consortium and nZVI-LDH. The initial removal of PCE was mainly dominated by the abiotic degradation and adsorption of nZVI-LDH, and biodegradation then played a major role in the exhaustion of nZVI-LDH. These results suggest that biodegradation coupled with nZVI-LDH has a great potential for applications in the remediation of chlorinated-solvent contaminated groundwater.