Safety, tolerability, and Plasmodium falciparum transmission-reducing activity of monoclonal antibody TB31F: a single-centre, open-label, first-in-human, dose-escalation, phase 1 trial in healthy malaria-naive adults.
Malaria elimination requires interruption of the highly efficient transmission of Plasmodium parasites by mosquitoes. TB31F is a humanised monoclonal antibody that binds the gamete surface protein Pfs48/45 and inhibits fertilisation, thereby preventing further parasite development in the mosquito midgut and onward transmission. We aimed to evaluate the safety and efficacy of TB31F in malaria-naive participants. In this open-label, first-in-human, dose-escalation, phase 1 clinical trial, healthy, malaria-naive, adult participants were administered a single intravenous dose of 0·1, 1, 3, or 10 mg/kg TB31F or a subcutaneous dose of 100 mg TB31F, and monitored until day 84 after administration at a single centre in the Netherlands. The primary outcome was the frequency and magnitude of adverse events. Additionally, TB31F serum concentrations were measured by ELISA. Transmission-reducing activity (TRA) of participant sera was assessed by standard membrane feeding assays with Anopheles stephensi mosquitoes and cultured Plasmodium falciparum gametocytes. The trial is registered with Clinicaltrials.gov, NCT04238689. Between Feb 17 and Dec 10, 2020, 25 participants were enrolled and sequentially assigned to each dose (n=5 per group). No serious or severe adverse events occurred. In total, 33 grade 1 and six grade 2 related adverse events occurred in 20 (80%) of 25 participants across all groups. Serum of all participants administered 1 mg/kg, 3 mg/kg, or 10 mg/kg TB31F intravenously had more than 80% TRA for 28 days or more, 56 days or more, and 84 days or more, respectively. The TB31F serum concentration reaching 80% TRA was 2·1 μg/mL (95% CI 1·9-2·3). Extrapolating the duration of TRA from antibody kinetics suggests more than 80% TRA is maintained for 160 days (95% CI 136-193) following a single intravenous 10 mg/kg dose. TB31F is a well tolerated and highly potent monoclonal antibody capable of completely blocking transmission of P falciparum parasites from humans to mosquitoes. In areas of seasonal transmission, a single dose might cover an entire malaria season. PATH's Malaria Vaccine Initiative.


Boron inhibits apoptosis in hyperapoptosis condition: Acts by stabilizing the mitochondrial membrane and inhibiting matrix remodeling.
An abnormally high apoptosis has been associated with a number of clinical conditions including embryonal malformations and various pathologies such as neuronal degeneration and diabetes. In this study, boron is reported to inhibit apoptosis in hyperapoptosis conditions as demonstrated in a model of hyperapoptosis. Boron is a metalloid which is present in food in small amounts and is suggested here to inhibit apoptosis by stabilizing the mitochondrial membrane structure, thus preventing matrix remodeling and the release of cytochrome c, an apoptosis-inducer protein from the mitochondrion. The protective effect was assessed by measuring the changes in mitochondrial membrane potential, the levels of cytochrome c and downstream activation of caspase 3, besides phosphatidylserine exposure on the cell surface and DNA damage. The study has implication in clinical conditions characterized by hyperapoptosis as seen in certain embryonal malformations and various pathologies.


The survival and removal mechanism of Sphingobacterium changzhouense TC931 under tetracycline stress and its' ecological safety after application.
Sphingobacterium changzhouense TC931 was isolated as a novel TC (tetracycline) removal bacterium through adsorption on extracellular polymerase substances (EPS) and cellular surface and biodegradation. TC biodegradation efficiency by strain TC931 was affected by solution initial pH and carbon source. Polysaccharides and hydrocarbons in EPS and cellular surface were responsible for TC biosorption. Eight possible biodegradation products were identified and the biodegradation pathway was proposed. Strain TC931 was rich in antibiotic resistance genes, and tetX-TC931 and antibiotics resistance genome island (GI) may be acquired via horizontal gene transfer in early evolutionary history. The GI was incomplete and may stable in strain TC931, but it could develop into an intact and transferability GI with help of other mobile genetic elements. This work offers a theoretical basis for understanding the survival and biodegradation mechanisms of S. changzhouense TC931 under TC stress, and offers an ecological safety assessment for its application in environmental bioremediation.


Changes in the pattern of aldehyde dehydrogenase activity in primary and metastatic adenocarcinomas of the human colon.
The activity of aldehyde dehydrogenase (ALDH) was measured in primary and metastatic human colonic adenocarcinomas. The enzyme was determined with either propionaldehyde and NAD (P-NAD) or with benzaldehyde and NADP(B-NADP). Primary colonic adenocarcinomas had levels of P-NAD activity similar to those of the adjacent normal mucosa, but relatively higher B-NADP activity. Also the metastatic colonic adenocarcinomas of the liver had lower P-NAD and higher B-NADP activity than the normal hepatic parenchyma. The level of ALDH was in general lower in the normal colonic mucosa, when compared to the liver. Histochemical staining of cryostat tissue sections revealed that the enzyme is exclusively confined to the epithelial cells of the glandular ducts of the colonic mucosa. This may explain, along with the significant anaplastic changes of the mucosa, the variation of ALDH activity detected in the homogenates of the primary and metastatic adenocarcinomas. However, the ratio of B-NADP activity in the adenocarcinomas versus the adjacent normal tissues was constantly and significantly high.


Clinical Outcomes of Warfarin Initiation in Advanced Chronic Kidney Disease Patients With Incident Atrial Fibrillation.
The aim of this study was to examine the efficacy and safety of warfarin initiation following the diagnosis of atrial fibrillation (AF) in patients with late-stage chronic kidney disease (CKD) who transitioned to dialysis. The clinical benefit of warfarin therapy for thromboprophylaxis after incident AF diagnosis in patients with late-stage CKD who are transitioning to dialysis is unknown. In this retrospective cohort analysis, the study population was a national cohort of 22,771 U.S. veterans with incident end-stage renal disease who developed incident AF before initiating renal replacement therapy. This study examined the association of warfarin therapy following the diagnosis of incident AF with ischemic cerebrovascular accidents (CVAs) (ischemic stroke or transient ischemic attack), ischemic CVA-related hospitalization, major bleeding events (gastrointestinal or intracranial bleeding), bleeding event-related hospitalizations, and post-dialysis, all-cause mortality in multivariable adjusted Cox regression analyses that adjusted for demographic characteristics and comorbidities. The mean ± SD age of the cohort was 73.5 ± 8.8 years, 13% were African American, and the mean CHA2DS2-VASc score was 5.7 ± 2.1. Of the overall cohort, 6,682 (29.3%) patients were started on warfarin during the follow-up period. The hazard ratios (95% confidence intervals) for ischemic CVA, bleeding events, and death for those started on warfarin were 1.23 (1.16 to 1.30), 1.36 (1.29 to 1.44), and 0.94 (0.90 to 0.97), respectively, compared with those who received no anticoagulation. Warfarin exposure was associated with higher risk for ischemic CVA and bleeding event-related hospitalizations. In patients with late-stage CKD who transitioned to dialysis, warfarin use was associated with higher risk of ischemic and bleeding events but a lower risk of mortality. Future studies such as those comparing warfarin with newer oral anticoagulant agents are needed to granularly define the net clinical benefit of anticoagulation therapy in patients with advanced CKD with incident AF.


Transient receptor potential channels as therapeutic targets.
Transient receptor potential (TRP) cation channels have been among the most aggressively pursued drug targets over the past few years. Although the initial focus of research was on TRP channels that are expressed by nociceptors, there has been an upsurge in the amount of research that implicates TRP channels in other areas of physiology and pathophysiology, including the skin, bladder and pulmonary systems. In addition, mutations in genes encoding TRP channels are the cause of several inherited diseases that affect a variety of systems including the renal, skeletal and nervous system. This Review focuses on recent developments in the TRP channel-related field, and highlights potential opportunities for therapeutic intervention.


Establishing a sorting protocol for healthcare databases.
Health information records in many countries, especially developing countries, are still paper based. Compared to electronic systems, paper-based systems are disadvantageous in terms of data storage and data extraction. Given the importance of health records for epidemiological studies, guidelines for effective data cleaning and sorting are essential. They are, however, largely absent from the literature. The following paper discusses the process by which an algorithm was developed for the cleaning and sorting of a database generated from emergency department records in Lebanon. Demographic and health related information were extracted from the emergency department records of three hospitals in Beirut. Appropriate categories were selected for data categorization. For health information, disease categories and codes were selected according to the International Classification of Disease 10th Edition. A total of 16,537 entries were collected. Demographic information was categorized into groups for future epidemiological studies. Analysis of the health information led to the creation of a sorting algorithm which was then used to categorize and code the health data. Several counts were then performed to represent and visualize the data numerically and graphically. The article describes the current state of health information records in Lebanon and the associated disadvantages of a paper-based system in terms of storage and data extraction. Furthermore, the article describes the algorithm by which health information was sorted and categorized to allow for future data analysis using paper records.


T-antigens in primary non-invasive and superficially invasive human urinary bladder tumors: the correlation to tumor recurrence and tumor progression. A mini-review.
As cellular carbohydrate structures are involved in multiple cellular functions, alterations in these structures have been studied in an effort to find markers and predictors of the clinical course of disease in human cancers. Special interest has been given to recurrence and progression of cancer disease. At present no such marker or predictor exists for the prediction of recurrence and progression of initially non-invasive (Ta) or superficially invasive (T1) human urinary bladder tumors. Over the years the T- (Thomsen-Friedenreich) antigen (the disaccharide Gal beta(1-3)GalNAc alpha(1-O)-R) has been investigated for its possible role as such a marker. An overview is given. It is concluded that there is a general, but not an individual correlation between T-antigen expression and recurrence or progression of initially non- or superficially invasive human bladder tumors.


Overlooked resources: the place of the library in visual science research.
Effective research should be based on familiarity with what has already been accomplished in the field. The best place to look for this information is a library, since even the most widely read professional may miss much that is relevant. Libraries not only provide access to their own holdings but assist the investigator by means of computerized literature searches and the use of indexes, abstracts, and other forms of printed reference material. Efficient use of library facilities can aid research and facilitate preparation of grant proposals.


Influence of dietary fat and zinc supplementation on the iron utilization in growing rats.
There is increasing evidence that the amount and type of dietary fat may modify the utilization of the trace element iron. The present study investigated the effect of high amounts of fat of different origin at marginal and high dietary zinc supply on the iron utilization. Growing male rats, assigned to 1 of 6 groups of 8 animals each were fed diets that contained either 7 or 100 microg zinc/g. These diets were enriched with 0 or 22% fat as beef tallow (BT) or as sunflower oil (SO) above the basal level of 3% soybean oil. Iron was added as ferrous sulfate at 60 microg/g of diet. The apparent iron absorption was markedly lower in the case of the high-fat diets at either zinc level. The BT diets resulted in significantly higher iron concentrations in the liver compared to both the SO and control diets. Hemoglobin and hematocrit were not influenced by any of the treatments. Although the high-fat diets reduced iron absorption, there was no evidence for lower iron status parameters in blood and tissues. In contrast, BT as a source of saturated fatty acids markedly elevated liver iron concentrations.


Safety and tolerability of a humanized rabbit monoclonal antibody (SSS07) in healthy adults: Randomized double-blind placebo-controlled single ascending dose trial.
SSS07, a humanized rabbit monoclonal antibody, can selectively block human tumor necrosis factor-α (TNF-α). The objective of this study was to assess the safety, tolerability, and relative immunogenicity of SSS07 after multiple single subcutaneous (SC) doses in healthy volunteers. A total of 71 healthy volunteers were randomized to six sequential ascending-dose groups (5, 15, 30, 50, 75, and 100 mg), and except for the 100 mg group that only had one subject who received a placebo, all of the other groups included two placebo-control subjects. Safety, tolerability, and immunogenicity were assessed by physical examinations, vital signs, electrocardiography (ECG), clinical laboratory tests, and plasma anti-drug antibody (ADA) over 28 days for each group. Their concentrations of TNF-α were also analyzed. Only after safety and tolerance were determined in the lower-dose groups was the next dose group initiated. The dose increments did not exceed 100 mg. No serious adverse events or dose-limited toxicity (DLT) were observed, so 100 mg was defined as the maximum tolerated dose (MTD). Overall, 71 AEs and 59 treatment-related adverse events (TRAEs) were reported in 36 (60.0%) and 30 (50.0%) volunteers, respectively, who received SSS07. All AEs and TRAEs were mild or moderate and expected based on previous results with similar types of drugs, without new safety concerns. Except for infections and administration site reactions, the frequency and intensity of the other TRAEs were similar for SSS07 and placebo. No severe acute immune reactions occurred. The lower dose's immunogenicity was stronger than the higher doses. The highest ADA titer was observed 3 to 6 months after administration. SSS07 was generally safe and well tolerated in healthy Chinese volunteers. Higher immunogenicity was observed at low SSS07 concentration levels. The infections and administration site conditions might have been related to the immunogenicity and the degree of inhibition of TNF-α. However, the existence of ADA did not appear to affect the safety of the subjects throughout the follow-up period. These findings could support further investigations of treatments with humanized monoclonal antibodies.


Different mechanisms for diastolic mitral regurgitation illustrated by three comparative cases.
Diastolic mitral regurgitation (DMR) has been reported in patients with AV block, aortic regurgitation, cardiomyopathies, and in patients with long filling periods in atrial tachyarrhythmias. The mechanism for DMR is a reversal in the atrioventricular gradient during diastole. However, because of its relatively low velocity, it may be difficult to diagnose noninvasively. We present three different cases of diastolic MR in 2:1 second-degree AV block, atrial flutter, and dilated cardiomyopathy, with different locations in diastole. Diastolic tricuspid regurgitation commonly accompanies DMR. Careful analysis of echocardiographical images related with online ECG is very important in order to delineate systolic and DMR, and their timing in systole and diastole.


Utility of the 10 Hounsfield unit threshold for identifying adrenal adenomas: Can we improve?
Current recommendations using Hounsfield units (HU) ≤ 10 to identify adrenal adenomas on unenhanced computed tomography (CT) miss 10-40% of benign adenomas. We sought to determine if changing HU threshold and adding absolute percent contrast washout (APW) criteria would identify adrenal adenomas better than current recommendations. Imaging characteristics were compared between patients with adenomas (n = 128) and those with non-adenomas (n = 54) after unilateral adrenalectomy. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated. Using HU ≤ 10 to identify adenomas had a sensitivity of 47.6%, specificity of 93.3% (AUC = 0.71, p < 0.001), PPV of 95.3%, and NPV of 58.1% for identifying adrenal adenomas. Applying HU ≤ 16 improved sensitivity (65.4%) without reducing specificity (93.3%) (AUC = 0.79, p < 0.001), PPV increased to 96.3%, and NPV decreased to 47.6%. Applying HU ≤ 16 as the initial criterion followed by APW > 60% for lesions exceeding 16 HU, sensitivity increased to 93.4%, specificity was 93.3% and PPV 96.6%, and NPV improved to 85.7% (AUC = 0.96, p < 0.001). Criteria of initial threshold of HU ≤ 16 followed by APW > 60% for lesions exceeding 16 HU yielded improved sensitivity and specificity in identification of adrenal adenomas.


Interleukin-1 in obesity-related low-grade inflammation: From molecular mechanisms to therapeutic strategies.
Since adipose tissue (AT) can upregulate pro-inflammatory interleukins (ILs) via storing extra lipids in obesity, obesity is considered the leading cause of chronic low-grade inflammation. These ILs can pave the way for the infiltration of immune cells into the AT, ultimately resulting in low-grade inflammation and dysregulation of adipocytes. IL-1, which is divided into two subclasses, i.e., IL-1α and IL-1β, is a critical pro-inflammatory factor. In obesity, IL-1α and IL-1β can promote insulin resistance via impairing the function of adipocytes and promoting inflammation. The current study aims to review the detailed molecular mechanisms and the roles of IL-1α and IL-1β and their antagonist, interleukin-1 receptor antagonist(IL-1Ra), in developing obesity-related inflammatory complications, i.e., type II diabetes (T2D), non-alcoholic steatohepatitis (NASH), atherosclerosis, and cognitive disorders. Besides, the current study discusses the recent advances in natural drugs, synthetic agents, and gene therapy approaches to treat obesity-related inflammatory complications via suppressing IL-1.


Medium-Term Follow-Up Outcomes of One-Stage Posterior Lumbosacral or Lumbopelvic Fixation in the Management of Lumbosacral Junction Tuberculosis in Adults.
To evaluate the medium-term outcomes of one-stage posterior lumbosacral or lumbopelvic fixation treatment of lumbosacral junction tuberculosis in adults. This retrospective study enrolled a total of 38 adult patients (24 males and 14 females) with an average age of 48.0 ± 13.0 years (range, 25-75 years) during the period from February 2008 to July 2015. All patients were treated by one-stage posterior debridement, interbody fusion, lumbosacral or lumbopelvic fixation, and postural drainage. After pedicle screw or iliac screw fixation, a hemi-laminectomy or laminectomy was performed on the severely damaged side of the lesion segment. Intervertebral bone grafting and intertransverse bone grafting were performed after clearing the focus of tuberculosis. All cases were followed up for at least 5 years. Intraoperative blood loss, operative time, erythrocyte sedimentation rate (ESR), pain intensity was assessed by visual analog scale (VAS) score; neurological function was assessed by Japanese Orthopaedic Association (JOA) score; quality of life was assessed by Oswestry Disability Index (ODI); functional outcome, lumbosacral angle, and fusion time were gathered and analyzed. All data expressed as mean ± standard deviation. During the 66.2 ± 4.4 months (range, 60-78 months) follow-up, all patients achieved clinical cure without severe complications. The intraoperative blood loss was 726.3 ± 151.9 mL (range, 400-1100 mL) and the operative time was 137.6 ± 22.5 min (range, 110-200 min). The ESR decreased to normal levels within (11.8 ± 2.6 mm/h) 3 months postoperatively. The VAS score significantly decreased from 6.8 ± 1.1 preoperatively to 0.8 ± 0.7 at the final follow-up (P < 0.01). The mean JOA improved from preoperative 18.5 ± 2.9 to 26.9 ± 1.1 at the last visit (P < 0.01). The mean ODI was 44.3 ± 6.7 and significantly decreased to 9.3 ± 1.9 at the final observation (P < 0.01). Patient-reported outcomes as measured by Kirkaldy-Willis criteria were excellent in 21 cases, good in 16 cases, and fair in one case; there were no poor outcomes. Lumbosacral angle increased from the preoperative values of 21.7° ± 1.8° to the postoperative values of 26.4° ± 1.4° (P < 0.01), with an angle loss of 1.2° ± 0.7° at the last follow-up. Bone fusion occurred on average 12.8 ± 1.9 months (range, 9-15 months) after surgery. No nonunion, pseudarthrosis, loosening or fracture of instruments occurred at the last follow-up. One-stage posterior debridement, interbody fusion, lumbosacral or lumbopelvic fixation, and postural drainage according to the severity of sacral destruction is an effective and highly safe procedure to treat lumbosacral junction tuberculosis in adults.


A systematic review and meta-analysis on the global prevalence of cattle microsporidiosis with focus on Enterocytozoon bieneusi: An emerging zoonotic pathogen.
Microsporidiosis, caused by the zoonotic eukaryote microsporidia spp. have serious health threat in high-risk groups, including immunocompromised individuals. Cattle plays a major role as reservoirs of microsporidia among the animals because of close-contact with humans. Hence, we aimed to evaluate the prevalence and genetic diversity of cattle microsporidiosis at a global scale through systematic review and meta-analysis approach. A comprehensive literature searches of published articles related to the molecular distribution of microsporidiosis in cattle was conducted between 1 January 1990 and 20 December 2020. The confidence intervals (95 %) and point estimates were calculated using the random-effects model. A total of 1809 was retrieved from the initial search, after exclusion of irrelevant articles 37 articles met inclusion criteria to be included for final analysis. The estimated pooled prevalence of cattle microsporidiosis was 14 % (CI: 11.5-17 %) worldwide. Accordingly, the calves had the highest prevalence 20 % (CI: 14.8-26.5 %). According to internal transcribed spacer (ITS) gene, Enterocytozoon bieneusi with genotypes BEB4 (22 studies), J (21 studies), and I (17 studies) were the highest reported genotypes. The present results highlight the role of cattle as reservoir hosts for human-infecting microsporidia. Strategies for control and prevention of these pathogens should be designed to mitigate the risk of cattle to human transmission.


Surgical Evacuation of Spontaneous Supratentorial Lobar Intracerebral Hemorrhage: Comparison of Safety and Efficacy of Stereotactic Aspiration, Endoscopic Surgery, and Craniotomy.
The safety and efficacy of craniotomy, endoscopic surgery, and stereotactic aspiration for surgical evacuation of spontaneous supratentorial lobar intracerebral hemorrhage (ICH) is yet uncertain. The present study analyzed the clinical and radiographic data from 99 patients with spontaneous supratentorial lobar ICH, retrospectively, to address this issue. Patients who underwent craniotomy, endoscopy surgery, or stereotactic aspiration were assigned to the craniotomy group (n = 31), endoscopy surgery group (n = 32), or stereotactic aspiration group (n = 36), respectively. The characteristics of all the enrolled patients at the time of admission were assimilated. Also, the therapeutic effects of the three surgical procedures were evaluated based on short-term outcomes within 30 days and long-term outcomes at 6 months after the ictus. The results showed that stereotactic aspiration and endoscopic surgery were associated with a superior clinical therapeutic effect in both short-term and long-term outcomes than craniotomy for the treatment of spontaneous supratentorial lobar ICH. Notably, severely affected patients with hematoma volume > 60 mL or Glasgow Coma Scale score 4-8 may benefit more from endoscopic surgery than the two other surgical procedures. The current findings demonstrate that both stereotactic aspiration and endoscopic surgery possess an apparent advantage over craniotomy for the evacuation of spontaneous supratentorial lobar ICH. The endoscopic surgery might be more safe and effective with higher evacuation rate, better functional neurological outcomes, and lower complication and mortality rates.


Pituitary corticotroph macrotumors. Diagnosis and treatment.
Pituitary corticotroph macrotumors occur in 10% to 50% of dogs with PDH. Clinical signs may be only those of hypercortisolism or may include neurologic signs such as stupor, inappetance, circling, or pacing. Currently, CT and MRI are the only tests that can confirm the presence of a pituitary macrotumor in these patients. Results of endocrine testing are not significantly different from those of dogs with a microtumor. When a macroscopic pituitary tumor is identified in a dog with neurologic signs, or if a larger tumor is found in a dog even in the absence of neurologic signs, radiation therapy is currently the treatment of choice. Unfortunately, success rates with treatment are variable. A better response may be seen if the tumor is smaller and neurologic signs are minimal or absent at the time of treatment.


Two faces of entropy and information in biological systems.
The article attempts to overcome the well-known paradox of contradictions between the emerging biological organization and entropy production in biological systems. It is assumed that quality, speculative correlation between entropy and antientropy processes taking place both in the past and today in the metabolic and genetic cellular systems may be perfectly authorized for adequate description of the evolution of biological organization. So far as thermodynamic entropy itself cannot compensate for the high degree of organization which exists in the cell, we discuss the mode of conjunction of positive entropy events (mutations) in the genetic systems of the past generations and the formation of organized structures of current cells. We argue that only the information which is generated in the conditions of the information entropy production (mutations and other genome reorganization) in genetic systems of the past generations provides the physical conjunction of entropy and antientropy processes separated from each other in time generations. It is readily apparent from the requirements of the Second law of thermodynamics.


Type 1 and type 2 herpes simplex virus in corneal cell cultures.
The pathogenicity of herpes simplex virus (HSV) in primary cultures of epithelia, stromal, and endothelial cells of rabbit corneas was studied at various incubation temperatures (30 degrees, 36 degrees, and 40 degrees C). We tested three strains each of type 1 (HSV-1) and type 2 (HSV-2). At all three temperatures, the epithelial cells appeared to be more susceptible to both HSV-1 and HSV-2 than the stromal and endothelial cells. In general, less HSV-1 was requered than HSV-2 to infect the same type of corneal cell at the same incubation temperature. At 40 degrees C, however, there was far less cell destruction by either HSV-1 or HSV-2 than at 30 degrees or 36 degrees C. This inhibition at 40 degrees C was more pronounced in the cells infected with HSV-2 than in those infected with HSV-1, and the inhibition was accompanied consistently by significant suppression of virus multiplication in the cells.


Comparison of fluorescence and light scattering based methods to assess formation and stability of protein-protein complexes.
Thermal shift methods such as differential scanning fluorimetry and differential static light scattering are widely used to identify stabilizing conditions for proteins that might promote crystallization. Here we report a comparison of the two methods when applied to optimization of buffer conditions for protein-protein complexes. Most of the protein complexes under study were amenable to analysis using these two techniques. Protein complexes behave towards thermal denaturation in a manner similar to single proteins, showing a more or less sharp transition consistent with a two-state model of unfolding. A comparison of the melting and aggregation temperatures for single components and the reconstituted complexes can provide additional evidence for complex formation and can be used to identify buffer conditions in which protein-protein complex formation is favored.


Microglia in developing white matter and perinatal brain injury.
Perinatal brain injury (PBI) to the developing white matter results in hypomyelination of axons and can cause long-term motor and cognitive deficits e.g. cerebral palsy. There are currently no approved therapies aimed at repairing the white matter following insult, underscoring the need to investigate the mechanisms underlying the pathogenesis of PBI. Microglia have been strongly implicated, but their function and heterogeneity in this context remain poorly understood, posing a barrier to the development of microglia-targeted therapies for white matter repair following PBI. In this review, we discuss the roles of microglia in normal white matter development and in PBI, and potential drug strategies to influence microglial responses in this setting.


Associations Between White Matter Hyperintensity Burden, Cerebral Blood Flow and Transit Time in Small Vessel Disease: An Updated Meta-Analysis.
Cerebral small vessel disease (SVD) is a major contributor to stroke and dementia, characterized by white matter hyperintensities (WMH) on neuroimaging. WMH are associated with reduced cerebral blood flow (CBF) cross-sectionally, though longitudinal associations remain unclear. We updated a 2016 systematic review, identifying 30 new studies, 27 cross-sectional (n = 2,956) and 3 longitudinal (n = 440). Cross-sectionally, 10/27 new studies (n = 1,019) included sufficient data for meta-analysis, which we meta-analyzed with 24 previously reported studies (n = 1,161), total 34 (n = 2,180). Our meta-analysis showed that patients with lower CBF had worse WMH burden (mean global CBF: standardized mean difference (SMD): -0.45, 95% confidence interval (CI): -0.64, -0.27). Longitudinally, associations between baseline CBF and WMH progression varied: the largest study (5 years, n = 252) found no associations, while another small study (4.5 years, n = 52) found that low CBF in the periventricular WMH penumbra predicted WMH progression. We could not meta-analyse longitudinal studies due to different statistical and methodological approaches. We found that CBF was lower in WMH than in normal-appearing white matter in an additional meta-analysis (5 cross-sectional studies; n = 295; SMD: -1.51, 95% CI: -1.94, -1.07). These findings highlight that relationships between resting CBF and WMH are complex. Further longitudinal studies analyzing regional CBF and subsequent WMH change are required to determine the role of CBF in SVD progression.


Maternal and fetal outcomes in pregnant females with rheumatic heart disease.
Cardiac diseases are seen in 1-3% of pregnancies. In developing countries rheumatic heart disease (RHD) contributes a major cause of cardiac disorders. To study the maternal and fetal outcome in women with valvular heart disease or prosthetic heart valve replacement secondary to RHD in a tertiary care center. The consecutive pregnant women with RHD attending our institute from May 2018 to August 2019 were included. A maternal adverse outcome was defined as cardiac death, new onset arrhythmia, heart failure, thromboembolic event, hospitalization for other cardiac reasons or cardiac intervention, aortic dissection, infective endocarditis and acute coronary syndrome. Fetal adverse outcome defined as fetal death, preterm birth, and low birth weight. Total 80 patients were included in this study, native RHD in 60(75%) and 20(25%) had mechanical prosthetic valve replacement. Maternal adverse event occurred in 34(42.5%), comprising of death in 1(1.2%), new onset AF 2(2.5%), 20(25%) underwent balloon mitral valvotomy, 3(3.7%) underwent mitral valve replacement, heart failure hospitalization in 7(8.7%). 1(1.2%) patient developed mitral valve infective endocarditis. Preterm delivery occurred in 19(23.7%), 7(8.7%) abortions and 1(1.2%) intrauterine death. Fetuses with low birth weight were 43(53.7%). Pregnancy with live birth occurred in 57(95%) women with valvular heart disease but no prosthesis and 16(80%) women with prosthetic valve disease. Women with rheumatic heart disease carry a high risk both for mother and fetus. Early diagnosis, close follow-up during pregnancy, early recognition of deterioration in symptoms and timely cardiac intervention can lead to good maternal or fetal outcome.


From staff nurse to nurse consultant: Survival Guide part 4: Surviving as a senior clinical nurse.
John Fowler, Educational Consultant, explores how to survive your nursing career.


TCF7L2 type 2 diabetes risk variant, lifestyle factors, and incidence of prostate cancer.
Variation in transcription factor 7-like 2 (TCF7L2), the strongest genetic risk factor for type 2 diabetes (T2D), may play a role in prostate cancer (PCa) depending on lifestyle factors. The aims of this study were to determine if TCF7L2 rs7903146 is associated with risk of PCa and if the association is modified by lifestyle factors independently of T2D status. We prospectively followed 8,558 men in the Malmö Diet and Cancer Study from baseline 1991-1996 until end of 2009. Cox regression models were used to assess the association between rs7903146 T2D-risk allele (T) and PCa. Effect modification by incident T2D status, fasting glucose levels, dietary, and lifestyle risk factors were tested. During follow-up 855 incident PCa cases were registered. We observed a non-significant tendency for the TCF7L2 variant to associate with higher risk of PCa, which was unaffected by adjustment for incident T2D (HR = 1.24; 95% CI: 0.96, 1.60; P = 0.079) but more pronounced among subjects who developed T2D (HR = 1.91, 95% CI: 0.88, 4.14; P = 0.064). In a sub-sample of hyperglycemic men we observed an increased risk of PCa among T-allele carriers (HR = 2.72, 95% CI: 1.22, 6.04; P = 0.014; P(interaction) = 0.056). T-allele carriers with higher number of lifestyle risk factors had an increased risk of PCa (P(interaction) = 0.006). We found no independent association between TCF7L2 rs7903146 and PCa risk. However, among hyperglycemic men we observed that the risk allele may increase risk of PCa. The association between rs7903146 and PCa risk may also be modified by lifestyle factors.


A deleted portion of one of the two xanthine dehydrogenase genes causes translucent larval skin in the oq mutant of the silkworm (Bombyx mori).
A silkworm mutant, oq, has translucent larval skin because it is deficient in xanthine dehydrogenase (XDH) activity and is unable to synthesize uric acid, which is normally accumulated in the larval epidermis and makes the skin white and opaque. Two XDH bands were found in zymograms of the silkworm fat body: an intense band (XDHalpha) and a faint one (XDHbeta). The oq mutant lacks only XDHalpha, which seemed to be the major source of XDH activity in the fat body. An 8-bp deletion found in BmXDH1, a silkworm XDH gene, generates a premature stop codon. The resulting truncated BmXDH1 protein lacks three molybdenum cofactor-binding domains necessary for enzyme activity. BmXDH2, the other XDH gene, does not show any apparent deficiencies. BmXDH1 expressed in yeast cells yielded an activity band with the same mobility as that of XDHalpha in zymograms. BmXDH1 of the oq mutant did not yield active XDH in yeast, while the activity was restored by filling in the deleted sequence. These results showed that BmXDH1 deletion in the oq mutant is responsible for the absence of significant XDH activity, resulting in the translucent larval skin of the mutant phenotype.


Comparison of whole-gut irrigation with golytely (GOL) and with a balanced electrolyte solution (BES) as preparation for colonoscopy.
The cleansing results of whole-gut irrigation with golytely (GOL) or with a balanced electrolyte solution (BES) were compared in otherwise unprepared patients. In one study 30 patients were randomly prepared either with 4 l GOL or with BES till a clear rectal effluent was obtained. Only 4/15 patients prepared with GOL, as compared with all 15 prepared with BES, had good or excellent cleansing results. In a second study, both solutions were infused in a double blind manner in 40 patients till rectal effluent was clear. No significant differences in the amount of fluid needed, the duration of lavage or degree of cleansing was found. However, significantly less fluid retention occurred with GOL.


Pesticide Exposure and Heat Exhaustion in a Migrant Agricultural Worker: A Case of Labor Trafficking.
To our knowledge, there are no published reports of heat exhaustion and pesticide exposure in a labor trafficked patient in the literature. Here we represent the case of J.C.J.L., who was labor trafficked. He presented to a local emergency department with heat exhaustion and pesticide exposure related to working conditions in a Mississippi corn field. Unfortunately, while he received medical treatment, his labor trafficking condition was missed. Emergency departments should be equipped to assess for human trafficking and connect trafficked persons with the resources they need. Emergency physicians should maintain a high index of suspicion for human trafficking among migrant workers presenting with occupation-related complaints.


Representation of social content in dorsomedial prefrontal cortex underlies individual differences in agreeableness trait.
Personality traits reflect key aspects of individual variability in different psychological domains. Understanding the mechanisms that give rise to these differences requires an exhaustive investigation of the behaviors associated with such traits, and their underlying neural sources. Here we investigated the mechanisms underlying agreeableness, one of the five major dimensions of personality, which has been linked mainly to socio-cognitive functions. In particular, we examined whether individual differences in the neural representations of social information are related to differences in agreeableness of individuals. To this end, we adopted a multivariate representational similarity approach that captured within single individuals the activation pattern similarity of social and non-social content, and tested its relation to the agreeableness trait in a hypothesis-driven manner. The main result confirmed our prediction: processing social and non-social content led to similar patterns of activation in individuals with low agreeableness, while in more agreeable individuals these patterns were more dissimilar. Critically, this association between agreeableness and encoding similarity of social and random content was significant only in the dorsomedial prefrontal cortex, a brain region consistently involved during attributions of mental states. The present finding reveals the link between neural mechanisms underlying social information processing and agreeableness, a personality trait highly related to socio-cognitive abilities, thereby providing a step forward in characterizing its neural determinants. Furthermore, it emphasizes the advantage of multivariate pattern analysis approaches in capturing and understanding the neural sources of individual variations.


Synaptic environment and extrasynaptic glutamate signals: The quest continues.
Behaviour of a mammal relies on the brain's excitatory circuits equipped with glutamatergic synapses. In most cases, glutamate escaping from the synaptic cleft is rapidly buffered and taken up by high-affinity transporters expressed by nearby perisynaptic astroglial processes (PAPs). The spatial relationship between glutamatergic synapses and PAPs thus plays a crucial role in understanding glutamate signalling actions, yet its intricate features can only be fully appreciated using methods that operate beyond the diffraction limit of light. Here, we examine principal aspects pertaining to the receptor actions of glutamate, inside and outside the synaptic cleft in the brain, where the organisation of synaptic micro-physiology and micro-environment play a critical part. In what conditions and how far glutamate can escape the synaptic cleft activating its target receptors outside the immediate synapse has long been the subject of debate. Evidence is also emerging that neuronal activity- and astroglia-dependent glutamate spillover actions could be important across the spectrum of cognitive functions This article is part of the special issue on 'Glutamate Receptors - The Glutamatergic Synapse'.


Probing the active site chemistry of β-glucosidases along the hydrolysis reaction pathway.
β-Glucosidases (EC 184.108.40.206) can be found in all domains of living organisms, where they play essential roles in the removal of terminal glucosyl residues from nonreducing ends of saccharides and glycosides. Two active site amino acid residues, a nucleophile and a proton donor, play key roles in the hydrolytic mechanism. Besides these two highly conserved catalytic residues, there are other conserved amino acids in the active site of β-glucosidases that make direct hydrogen bonds to the glycosyl moiety at the -1 subsite. In this study, the catalytic mechanism of a GH1 β-glucosidase (BGlu1) is systematically studied. On the basis of the quantum mechanical studies, the side chain of Tyr315 in an interaction with both O5 of the glucose ring and the nucleophilic glutamate contributes significantly to the energy profile. Glu440 and the conserved Asn175 are the other residues in the polar interaction with -1 glucose with considerable influence on the free energy of the reaction. Gln29, His130, and Trp441, which also form hydrogen bonds to the glycosyl moiety, are found to have relatively a minor effect on the reaction. Different arrangements of active site residues in the high-level [quantum mechanics (QM)] and low-level [molecular mechanics (MM)] regions during the hybrid QM/MM calculations indicate that Tyr315 lowers the energy barrier in the deglycosylation step (by 11.95 kcal/mol) while Glu440 mainly reduces the energy barrier of the glycosylation step. Exclusion of either of these two residues from the QM region results in deviation of the geometric parameters of the enzyme-substrate complex from those expected for the preactivated distorted structure of the substrate.


A micro-electrode study of peripheral neuropathy in man. Part 1. Responses to single graded stimuli.
Multi-unit micro-electrode recording were obtained from sensory fascicles of the sural and median nerves of 12 control subjects and of 28 patients with peripheral neuropathy. Spontaneous activity and mass responses to mechanical and electrical stimuli were examined. Mechanoreceptor function appeared normal but there was a reduced number of responsive receptors in peripheral neuropathy. The electrical activation threshold of nerve fibres of all conduction velocities was increased in neuropathy and a greater number of fibres needed to be activated for preception to occur. Clinical sensory impairment was associated with a reduction in size of the initial compound action potential of the maximal evoked neurogram and with dispersion of fibre responses. Pathological slowing of fibre conduction velocity was demonstrated in demyelinating neuropathy but in most cases of axomal degeneration the changes in velocity could have been due either to a reduced number of fast conducting fibres, or to conduction block. No changes were observed in C-fibre activity in these patients.


Prevalence of IgM anti-HBc among HBsAg carriers in Okinawa, Japan.
To evaluate the presence of IgM antibody to hepatitis B core antigen (IgM anti-HBc) in hepatitis B surface antigen (HBsAg) carriers, serial serum specimens of 698 carriers in Okinawa, Japan, from infants to adults, were studied by radioimmunoassay. IgM anti-HBc was detected in 7.6% of these carriers, with no difference between the sexes. The prevalence of IgM anti-HBc was higher in the age groups 0-9, 50-59 and over 60 than in the age group 20-29 and 30-39 years. In hepatitis B e antigen (HBeAg) positive carriers, the prevalence of IgM anti-HBc was 15.4%, a value significantly higher than in the HBeAg-negative carriers at 6.6%. In carriers with liver damage, the prevalence of IgM anti-HBc was 33.3%, a level significantly higher than the 6.3% in carriers without liver damage. However, IgM anti-HBc was detected in 34 carriers with neither HBeAg nor liver damage. These carriers are being closely followed. We discussed the presence of IgM anti-HBc in association with HBeAg or liver damage. The presence of IgM anti-HBc among HBsAg carriers was closely associated with liver damage.


Clinicopathological characteristics in large, non-polypoid colorectal adenomas with granule-aggregating appearance.
Endoscopically, most large, non-polypoid colorectal adenomas have a granule-aggregating appearance, made up of elevations of small, flat lesions projecting above the surrounding mucosa. In this study we investigated the clinicopathological characteristics in 26 cases of such tumours and proposed the term 'granule-aggregating tumour' (GAT). Patients with GATs (16 men and 10 women) had a mean age of 64.3 years (range, 38-83 years). The mean diameter of the GATs was 28 mm (range, 12-62 mm). Histologically, GATs were diagnosed as tubular (15 cases) or tubulovillous (11 cases) adenomas without submucosal invasion. These tumours had a surface morphology comprised mainly of small, flat elevations or granular structures, measuring 1.2 +/- 0.3 mm in diameter. Of the 26 patients with GATs, 19 (73.1%) were asymptomatic and 11 of these 19 cases (57.9%) were detected by a faecal occult blood test. In nine of the 26 patients (34.6%) GATs were accompanied by colorectal cancers arising at other sites. GATs show typical endoscopic features, often lack symptoms and are frequently accompanied by other cancers in other organs. An awareness of the existence of GATs should assist in the screening, prevention and therapy of colorectal tumours.


Circulating estradiol and the activation of male and female copulatory behavior in Japanese quail (Coturnix japonica).
Previous experiments using systemic and preoptic area (POA) hormone treatments have shown that aromatization of testosterone (T) to estrogen (E) is essential for activation of male-typical copulatory behavior in castrated male Japanese quail (Coturnix japonica). Two experiments were conducted to determine whether circulating estrogen levels characteristic of normal intact males are high enough to activate male-typical or female-typical copulatory behavior. In Experiment 1, blood samples were drawn every 4 hr from groups of sexually active male quail housed under a 16L:8D light-dark cycle, and assayed for estradiol (E2) concentration. The mean +/- SEM serum E2 was 54.2 +/- 3.6 pg/ml, and no daily cycle in serum E2 was seen. The males were then tested for sexual behavior; 88% mounted females, and 23% crouched when mounted by males. In Experiment 2, 51 males were castrated and implanted with Silastic tubes containing estradiol benzoate (EB) and/or cholesterol designed to produce five different levels of serum E2, then tested for male- and female-typical copulatory behavior and bled. The serum E2 in EB-implanted quail which mounted (253 +/- 30 pg/ml) was significantly higher than that of intact quail in Experiment 1, and only 10.2% of intact males had serum E2 as high as the minimum associated with mounting in EB-implanted males. These results show that serum E2 levels in intact males are not high enough to support male-typical copulation, and that aromatization in the POA to produce locally high E2 levels may be required. In addition, it was found that the threshold serum E2 to elevate receptivity significantly was 3.6 times the intact male level, and only slightly higher than serum E2 reported for intact females. Thus the lack of receptivity in intact males is probably due to insufficient circulating E2, and the male is not defeminized with respect to sensitivity to E2 for activation of receptivity.


Lysis of interarytenoid synechia (Type I Posterior Glottic Stenosis): vocal fold mobility and airway results.
The Type I Posterior Glottic Stenosis (PGS-I) is a well-described but uncommon clinical entity. Despite this, there is little known about the outcome of surgical treatment. Retrospective case series. Thirteen cases met inclusion criteria. All but one patient had a tracheostomy at the time of initial evaluation. At the postoperative visit, seven patients (54%) had completely normal vocal fold motion. Of the verbal patients, 6 (50%) had normal vocal function as reported by both the patient/caregiver and the physician, and 10 (83%) patients were successfully decannulated. Patients with an isolated interarytenoid synechia have an excellent prognosis with regard to decannulation. Although many patients regain normal vocal fold motion and a return to their preintubation vocal function, a significant proportion can have persistent deficits in vocal fold mobility and some level of dysphonia. This report represents the largest known series of PGS-I cases.


Prevalence of porcine respiratory pathogens in slaughterhouses in Shanxi Province, China.
Porcine respiratory diseases remain the biggest challenge in pig-based food production and are a public health concern. Despite control measures, persistent outbreaks have been reported worldwide. To establish an early detection mechanism for pig farm disease outbreaks based on slaughterhouse risk and environmental assessment. We investigated the prevalence and risk factors of porcine respiratory disease-causing pathogens including Mycoplasma hyopneumoniae (MHP), porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV) and Haemophilus parasuis (HPS). Polymerase chain reaction (PCR) was used to analyse the lungs of 491 pigs from 19 slaughterhouses across 11 cities in Shanxi Province, China. PCR detected MHP, PCV2, PPRSV and HPS in 76.99%, 67.00%, 11.82% and 19.55% of the samples, respectively; 10.12% were negative for all four pathogens. Co-positivity rates for two and three pathogens were identified. The results confirmed significant correlations between PCV2 and MHP (p = .001, p < .05), HPS and PCV2 (p = .01, p < .05) and MHP and PRRSV (p = .01, p < .05). No significant correlation was observed between HPS and MHP (p = .067, p > .05). Positive MHP and PCV2 rates were low in areas with high vegetation coverage. The overall pathogen positivity rate was higher in both lower and higher temperature environments. Interactions among pathogens may increase disease severity. Furthermore, environmental assessment and pathogen surveillance within pig slaughterhouses can be an effective approach for early detection and mitigation of new disease threats before broad dissemination occurs among a herd.


Genetic diversity in Sargasso Sea bacterioplankton.
Bacterioplankton are recognized as important agents of biogeochemical change in marine ecosystems, yet relatively little is known about the species that make up these communities. Uncertainties about the genetic structure and diversity of natural bacterioplankton populations stem from the traditional difficulties associated with microbial cultivation techniques. Discrepancies between direct counts and plate counts are typically several orders of magnitude, raising doubts as to whether cultivated marine bacteria are actually representative of dominant planktonic species. We have phylogenetically analysed clone libraries of eubacterial 16S ribosomal RNA genes amplified from natural populations of Sargasso Sea picoplankton by the polymerase chain reaction. The analysis indicates the presence of a novel microbial group, the SAR11 cluster, which appears to be a significant component of this oligotrophic bacterioplankton community. A second cluster of lineages related to the oxygenic phototrophs--cyanobacteria, prochlorophytes and chloroplasts--was also observed. However, none of the genes matched the small subunit rRNA sequences of cultivated marine cyanobacteria from similar habitats. The diversity of 16S rRNA genes observed within the clusters suggests that these bacterioplankton may be consortia of independent lineages sharing surprisingly distant common ancestors.


Towards a molecular understanding of the overlapping and distinct roles of UBQLN1 and UBQLN2 in lung cancer progression and metastasis.
The Ubiquilin family of proteins (UBQLN) consists of five related proteins (UBQLN1-4 and UBQLNL) that all contain ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains. UBQLN1 and UBQLN2 are the most closely related and have been the most well-studied, however their biochemical, biological and cellular functions are still not well understood. Previous studies from our lab reported that loss of UBQLN1 or UBQLN2 induces epithelial mesenchymal transition (EMT) in lung adenocarcinoma cells. Herein, we showed that loss of UBQLN1 and/or UBQLN2 induces cellular processes involved in tumor progression and metastasis, including proliferation, clonogenic potential and migration in lung adenocarcinoma cells. In fact, following simultaneous loss of both UBQLN1 and UBQLN2 many of these processes were further enhanced. To understand the molecular mechanisms by which UBQLN1 and UBQLN2 loss could be additive, we performed molecular, biochemical and RNAseq analyses in multiple cellular systems. We identified overlapping and distinct gene sets and pathways that were altered following loss of UBQLN1 and/or UBQLN2. We have also begun to define cell type specific gene regulation of UBQLN1 and UBQLN2, as well as understand how loss of either gene can alter differentiation of normal cells. The data presented here demonstrate that UBQLN1 and UBQLN2 perform similar, but distinct molecular functions in a variety of cell types.


Applications of Artificial Intelligence to Office Laryngoscopy: A Scoping Review.
This scoping review aims to provide a broad overview of the applications of artificial intelligence (AI) to office laryngoscopy to identify gaps in knowledge and guide future research. Scoping Review. Searches for studies on AI and office laryngoscopy were conducted in five databases. Title and abstract and then full-text screening were performed. Primary research studies published in English of any date were included. Studies were summarized by: AI applications, targeted conditions, imaging modalities, author affiliations, and dataset characteristics. Studies focused on vocal fold vibration analysis (43%), lesion recognition (24%), and vocal fold movement determination (19%). The most frequently automated tasks were recognition of vocal fold nodules (19%), polyp (14%), paralysis (11%), paresis (8%), and cyst (7%). Imaging modalities included high-speed laryngeal videos (45%), stroboscopy (29%), and narrow band imaging endoscopy (7%). The body of literature was primarily authored by science, technology, engineering, and math (STEM) specialists (76%) with only 30 studies (31%) involving co-authorship by STEM specialists and otolaryngologists. Datasets were mostly from single institution (84%) and most commonly originated from Germany (23%), USA (16%), Spain (9%), Italy (8%), and China (8%). Demographic information was only reported in 39 studies (40%), with age and sex being the most commonly reported, whereas race/ethnicity and gender were not reported in any studies. More interdisciplinary collaboration between STEM and otolaryngology research teams improved demographic reporting especially of race and ethnicity to ensure broad representation, and larger and more geographically diverse datasets will be crucial to future research on AI in office laryngoscopy. NA Laryngoscope, 132:1993-2016, 2022.


METTL14-Mediated miR-30c-1-3p Maturation Represses the Progression of Lung Cancer via Regulation of MARCKSL1 Expression.
Lung cancer (LC) is a pulmonary malignant tumor with extremely low 5-year survival rate. N6-methyladenosine (m6A) is confirmed to regulate diverse pathophysiological processes including cancers. Methyltransferase-like 14 (METTL14) is an important RNA methyltransferase in m6A modification. However, researches on the regulatory mechanism of METTL14 on LC progression are relatively rare. Tumor xenograft experiment was conducted to investigate the effect of METTL14 on LC in vivo. The relative expression of METTL14, miR-30c-1-3p, and myristoylated alanine-rich C kinase substrate-like protein-1 (MARCKSL1) in LC tissues and/or cell lines was determined using qRT-PCR. Western blot assay was used to measure the protein levels of METTL14 and MARCKSL1 in tumor xenograft model and/or LC cell lines. MTT, wound healing, and transwell assays were performed to detect LC cell viability and metastasis. RNA immunoprecipitation assay and qRT-PCR were used to verify the effects of METTL14 on pri-miR-30c-1-3p. The relationship between miR-30c-1-3p and MARCKSL1 was confirmed by the dual-luciferase reporter assay. METTL14 was remarkably downregulated in LC tissues and cell lines. METTL14 mediated the maturation of miR-30c-1-3p. The overexpressed METTL14 and overexpressed miR-30c-1-3p suppressed the cell viability and metastasis in LC. Meanwhile, the increased METTL14 also repressed the growth of tumor xenograft in vivo. In addition, MARCKSL1 was confirmed to be the target gene of miR-30c-1-3p. High expression of MARCKSL1 and low expression of miR-30c-1-3p reversed the suppressive effects of METTL14 overexpression on cell viability and metastasis. METTL14 promoted the maturation of miR-30c-1-3p and mediated MARCKSL1 expression to inhibit the progression of LC. This study may provide a new insight for the LC clinical therapy.


Experimental infection of Thailand Taenia (Chiengmai strain) in domestic animals.
Twenty-five gravid proglottides of a Thailand Taenia were obtained from a patient in Chiengmai, Thailand, and brought to our laboratory. The tapeworm was determined to be T. saginata-like by counting uterine branches (mean number 16, range 12-19 on each side). The eggs from these proglottides remained infective under storage at room temperature for 14 days followed by refrigeration (4-8 degrees C) for 131 days. Eight Small-Ear-Miniature pigs and two Holstein calves were each fed with 3000 eggs and sacrificed 12-76 days afterwards. Six pigs became infected and 16 cysticerci were recovered from the livers. Thirteen degenerated/calcified cysticerci were also recovered from the livers of the two calves. More cysticerci were found in the liver parenchyma (55%) than on the liver surface (45%) of the infected animals. Measurements of length, width, diameters of protoscolex, rostellum and sucker and hooklet pattern show that Thailand Taenia is similar to Taenia from Taiwan, Korea and Indonesia but different from T. saginata and T. solium. These findings indicate that Thailand Taenia, Taiwan Taenia, Korea Taenia, and Indonesia Taenia may be of the same species or sub-species.


Demonstration of a combined deficiency of xanthine oxidase and aldehyde oxidase in xanthinuric patients not forming oxipurinol.
Genetic heterogeneity has been suggested in xanthinuria from the hitherto unexplained ability of some patients with this hereditary disorder to convert allopurinol to its active metabolite oxipurinol--an activity generally attributed to xanthine oxidase. This study provides evidence that the enzyme aldehyde oxidase is also deficient in xanthinuric patients not converting allopurinol to oxipurinol, whereas a xanthinuric patient with normal formation of oxipurinol had normal aldehyde oxidase activity. It is concluded that the enzyme aldehyde oxidase is the principal enzyme responsible for the formation of oxipurinol in man.


Absent pyramidal eminence and stapedial tendon associated with congenital stapes footplate fixation: Intraoperative and radiographic findings.
Report an association between congenital stapes footplate fixation (CSFF) and radiological absence of the pyramidal eminence and stapedial tendon. Children and adults with intraoperatively confirmed CSFF and an absent stapedial tendon. Computed tomography (CT); exploratory tympanotomy with stapedotomy. Absence of a pyramidal eminence and stapedial tendon aperture identified on preoperative CT that was confirmed intraoperatively. Eight patients with intraoperative confirmation of CSFF and absent stapedial tendon were retrospectively identified. The average preoperative bone conduction and air conduction pure tone averages were 19.6 dB (SD 15.6 dB) and 55.9 dB (SD 23.6 dB), respectively. The average air-bone gap was 36.3 dB (SD 17.9 dB) preoperatively. In the seven patients who underwent preoperative CT, all were consistently identified to have an absent or hypoplastic pyramidal eminence and absent stapedial tendon aperture at the pyramidal eminence. In six cases, the stapedial footplate appeared normal, while in one case the footplate appeared abnormal which correlated with severe facial nerve prolapse observed intraoperatively. All eight cases underwent exploratory tympanotomy and demonstrated intraoperative stapes footplate fixation, absent stapedial tendon and either absent or hypoplastic pyramidal eminence, which correlated with preoperative CT findings. This study identifies a clinically pragmatic association between an absent pyramidal eminence identified on high-resolution CT and the diagnosis of CSFF. In a condition that otherwise generally lacks distinctive radiological features, the absence of a pyramidal eminence on CT in a patient with nonprogressive, congenital conductive hearing loss may strengthen clinical suspicion for CSFF.


Exploring the anticancer properties of a new nicotinamide analogue: Investigations into in silico analysis, antiproliferative effects, selectivity, VEGFR-2 inhibition, apoptosis induction, and migration suppression.
This study focuses on the development and evaluation of (E)-N-(3-(1-(2-(4-bromobenzoyl)hydrazono)ethyl)phenyl)nicotinamide (BHEPN) as a potential inhibitor of Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2). Computational investigations as density function theory (DFT), docking, molecular dynamics (MD) simulations, and ADMET) in addition to in vitro (VEGFR-2 inhibition, cytotoxicity against HepG2 and MCF-7 cancer cell lines, selectivity index, cells cycle analysis, apoptosis investigation, and cells migration assay) studies were conducted. DFT calculations determined the three-dimensional structure and indicated the reactivity of BHEPN. Molecular docking, and MD simulations analysis showed the BHEPN's binding affinity and its potential as a VEGFR-2 inhibitor. ADMET assessments predicted BHEPN's safety and drug-like characteristics. In vitro investigations confirmed the inhibition of VEGFR-2 with an IC50 value of 0.320 ± 0.012 µM. BHEPN also exhibited remarkable cytotoxic effects against HepG2 and MCF-7 cancer cell lines, with IC50 values of 0.19 ± 0.01 µM and 1.18 ± 0.01 µM, respectively, outperforming Sorafenib's IC50 values (2.24 ± 0.06 µM and 3.17 ± 0.01 µM), respectively. Notably, BHEPN displayed a higher IC50 value of 4.11 ± 0 µM against the non-carcinogenic Vero cell lines, indicating selectivity index values of 21.6 and 3.4 against the tested cancer cell lines, respectively. In a flow cytometry assay, BHEPN induced HepG2 cell cycle arrest at the G1/S phase. Moreover, BHEPN increased the incidence of early and late apoptosis in HepG2 cell lines (from 1.38% and 0.22%) in control cells to (4.11-26.02%) in the treated cells, respectively. Additionally, the percentage of necrosis raised to 13.39%, in contrast to 0.62% in control cells. Finally, BHEPN was able to reduce the migration and wound healing abilities in HepG2 cells to 38.89% compared to 87.92% in untreated cells after 48 h. These in vitro results aligned with the computational predictions, providing strong evidence of BHEPN's efficacy and safety in anticancer applications. BHEPN is a promising candidate for the development of novel anticancer agents through further in vitro and in vivo investigations.


Heterogeneity of Dietary practices in India: current status and implications for the prevention and control of type 2 diabetes.
Diet is one of the important modifiable factors in prevention of type 2 diabetes (T2D), making it important to understand geographical variations of food consumption pattern, their similarities and differences across various regions. Asian Indian diet patterns are mostly carbohydrate-based and with vast regional diversity. Staple food, food groups consumed, meat consumption pattern, type of fermented foods, food preparations, type of cooking oil used and food ingredients vary with different regions of India. There has been a slow transition from consumption of coarse grains to refined grains owing to socio-economic, cultural and other factors. Consumption of fruits and vegetables, fats, ready-to-eat foods and sugar is higher in urban population whereas consumption of carbohydrates in the form of cereals and millets is higher among the rural population. Cereal grains followed by pulses and legumes are main sources of protein, given that the frequency of meat consumption is low even among non-vegetarians in India compared to other countries. Overall, there is a tendency towards consumption of calorie-dense foods at the cost of food diversity, which may also result in micronutrient deficiencies as well as development of T2D and related metabolic diseases. Public health strategies and policy level decisions involving stakeholders with diet and lifestyle modification as focal points are absolute priorities to prevent and manage the burden of obesity and T2D in India.


Effect of hormone replacement therapy on bone formation quality and mineralization regulation mechanisms in early postmenopausal women.
Post-menopausal osteoporosis is characterized by a negative imbalance between bone formation and bone resorption resulting in a net bone loss, increasing the risk of fracture. One of the earliest interventions to protect against this was hormonal replacement therapy (HRT). Bone strength depends on both the amount and quality of bone, the latter including compositional / material and structural properties. Bone compositional / material properties are greatly dependent on both patient-, and tissue-age. Raman spectroscopy is an analytical tool ideally suited for the determination of bone compositional / material properties as a function of tissue age as it is capable of analyzing areas ~1 × 1 μm2 in tetracycline labeled bone forming areas. Using such analysis of humeri from an ovariectomized primate animal model, we reported that loss of estrogen results in alteration in the mineralization regulation mechanisms by osteoid organic matrix attributes at actively forming bone surfaces. In the present work, we used Raman microspectroscopic techniques to compare osteoid and youngest mineralized tissue composition, as well as relationships between osteoid organic matrix quality and quality attributes of the earliest mineralized tissue in paired iliac crest biopsies obtained from early postmenopausal women before and after two years of HRT therapy. Significant correlations between osteoid proteoglycans, sulfated proteoglycans, pyridinoline, and earliest mineralized tissue mineral content were observed, suggesting that in addition to changes in bone turnover rates, HRT affects the osteoid composition, mineralization regulation mechanisms, and potentially fibrillogenesis.


Localization of cyanine dye binding to brush-border membranes by quenching of n-(9-anthroyloxy) fatty acid probes.
The location and orientation of 3,3'-dipropylthiodicarbocyanine (diS-C3-(5)) binding sites in renal brush-border membrane vesicles was examined from the quenching of n-(9-anthroyloxy) fatty acid (n-AS) fluorescence. Based on previous kinetic studies (Cabrini, G. and Verkman, A.S. (1986) J. Membrane Biol. 90, 163-175) monomeric aqueous diS-C3-(5) binds to brush-border membrane vesicles (BBMV) by an initial 6 ms association to form bound monomer, a 30-40 ms equilibrium between bound monomer (M) and bound dimer (D), and a 1-1.3 s translocation of D from the outer to inner membrane leaflet. Based on Stern-Volmer and lifetime analyses, M and D quench the fluorescence of the n-AS probes by a collisional mechanism. At low [diS-C3-(5)]/[BBMV] (R), where M predominates, the n-AS quenching efficiencies (Q) are similar (n = 2-16); at high R, where D predominates, Q increases with n (16 greater than 12 much much greater than 6 greater than 2), suggesting that M is oriented parallel, and D perpendicular, to the phospholipid chains deep within the membrane. Mixture of diS-C3-(5) with brush-border membrane vesicles containing n-AS in a stopped-flow apparatus gave a biexponential fluorescence decrease (excitation 390 nm, emission above 450 nm) with time constants 30-40 ms and 1-1.5 s; there was no 6 ms quenching process. These findings are incorporated into a model in which diS-C3-(5) adheres loosely to the outer membrane surface in 6 ms, binds parallel to the membrane phospholipid in 30-40 ms, dimerizes and rotates by 90 degrees in much less than 30 ms, and translocates to the opposite half of the bilayer in 1-15 s.


4-hydroxy estrogen induces DNA damage on codon 130/131 of PTEN in endometrial carcinoma cells.
Catechol estrogens, such as 4-hydroxyestradiol (4-OHE2), are estrogen metabolites that form DNA adducts and may induce mutations and subsequent cell transformation in mammary cells; however, little is known about their roles in endometrial carcinogenesis. Furthermore, it remains unclear whether 4-OHE2 is able to induce DNA damage on specific genes involved in carcinogenesis or a 'pro'-mutation status such as microsatellite instability (MSI). Therefore, we modified terminal transferase-dependent PCR by the application of a capillary sequencer to detect DNA damage at the single base level. Using this method, we demonstrated that 4-OHE2 directly induced DNA damage on codon 130/131 in exon 5 of PTEN, which is a mutation hot spot for PTEN in endometrial carcinoma. Whereas, both estradiol and 4-OHE2 treatment did not affect MSI status in immortalized endometrial glandular cells. 4-OHE2 might contribute to endometrial carcinogenesis by inducing PTEN mutation on codon 130/131.


A simple and rapid method for extraction and measurement of circulating sphingolipids using LC-MS/MS: a targeted lipidomic analysis.
Sphingolipids are a class of lipids with high structural diversity and biological pleiotropy. Mounting evidence supports a role for sphingolipids in regulating pathophysiology of cardiometabolic diseases, and they have been proposed as potential cardiometabolic biomarkers. Current methods for quantifying sphingolipids require laborious pretreatment and relatively large sample volumes, and cover limited species, hindering their application in epidemiological studies. Herein, we applied a time-, labor-, and sample-saving protocol simply using methanol for plasma sphingolipid extraction. It was compared with classical liquid-liquid extraction methods and showed significant advantages in terms of simplicity, sphingolipid coverage, and sample volume. By coupling the protocol with liquid chromatography using a wide-span mobile phase polarity parameter and tandem mass spectrometry operated in dynamic multiple reaction monitoring mode, 37 sphingolipids from 8 classes (sphingoid base, sphingoid base phosphate, ceramide-1-phosphate, lactosylceramide, hexosylceramide, sphingomyelin, ceramide, and dihydroceramide) were quantified within 16 min, using only 10 μL of human plasma. The current method showed good performance in terms of linearity (R2 > 0.99), intra- and interbatch accuracy (70-123%) and precision (RSD < 12%), matrix effect (91-121%), recovery (96-101%), analyte chemical stability (deviation < 19%), and carryover (< 16%). We successfully applied this method to quantify 33 detectable sphingolipids from 579 plasma samples of an epidemiological study within 10 days. The quantified sphingolipid concentrations were comparable with previous studies. Positive associations of ceramide C22:0/C24:0 and their precursors with homeostasis model assessment of insulin resistance suggested that the synthesis of the ceramides might be involved in insulin resistance. This novel method constitutes a simple and rapid approach to quantify circulating sphingolipids for epidemiological studies using targeted lipidomic analysis, which will help elucidate the sphingolipid-regulated pathways underlying cardiometabolic diseases.


Cardiovascular changes associated with decreased aerobic capacity and aging in long-distance runners.
Fifty-five male runners aged between 30 to 80 years were examined to determine the relative roles of various cardiovascular parameters which may account for the decrease in maximal oxygen uptake (VO2max) with aging. All subjects had similar body fat composition and trained for a similar mileage each week. The parameters tested were VO2max, maximal heart rate (HRmax), cardiac output (Q), and arteriovenous difference in oxygen concentration (Ca-Cv)O2 during graded, maximal treadmill running. Average body fat and training mileage were roughly 12% and 50 km.week-1, respectively. The average 10-km run-time slowed significantly by 6.0%.decade-1 [( 10-km run-time (min) = 0.323 x age (years) + 24.4] (n = 49, r = 0.692, p less than 0.001]. A strong correlation was found between age and VO2max [( VO2max (ml.kg-1.min-1) = -0.439 x age + 76.5] (n = 55, r = -0.768, p less than 0.001]. Thus, VO2max decreased by 6.9%.decade-1 along with reductions of HRmax (3.2%.decade-1, p less than 0.001) and Q (5.8%.decade-1, p less than 0.001), while no significant change with age was observed in estimated (Ca-Cv)O2. It was concluded that the decline of VO2max with aging in runners was mainly explained by the central factors (represented by the decline of HR and Q in this study), rather than by the peripheral factor (represented by (Ca-Cv)O2).


Novel combretastatin A-4 derivative XN0502 induces cell cycle arrest and apoptosis in A549 cells.
Combretastatin A-4 (CA-4) is a tubulin-binding compound currently in phase II trial as a tumor vascular-targeting agent. The present study evaluates the anti-tumor activities and establishes the mechanism of the action of 4-(4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-pyrazol-3-amine(XN0502), a novel synthesized CA-4 analogue, in an effort towards finding the favorable therapeutics of CA-4 derivatives. XN0502 is characterized by its more potent anti-proliferative activities against non-small cell lung cancer A549 cells (IC(50): 1.8 +/- 0.6 microM), than that on the normal human liver HL-7702 cells (IC(50): 9.1 +/- 0.4 microM). Of note, using tubulin polymerization assay, western blot and immuofluorescence analyses, XN0502 was showed to inhibit microtubule assembly at both molecular and cellular levels in A549 cells. Further studies indicated that XN0502 induced time- and dose-dependent G2/M arrest, accompanying with the reduction of CDC2/p34 expression and the downregulation of CDK7. The protein level alteration and the nuclear translocation of cyclinB1 were observed, denoting the M phase arrest in XN0502-treated cells. Moreover, XN0502 caused caspase-mediated apoptosis, as indicated by the cleavage of PARP, the reduction of procaspase-3 and procaspase-9, and the down-regulation of XIAP. Taken together, the current study demonstrates that the novel CA-4 analogue XN0502 is a promising anti-cancer agent with potent G2/M arrest- and apoptotic-inducing activities via targeting tubulin deserving further research and development, and helps provide data for exploiting new CA-4 analogues.


Stress analysis of the implants in transforaminal lumbar interbody fusion under static and vibration loadings: a comparison between pedicle screw fixation system with rigid and flexible rods.
The use of a pedicle screw fixation system with rods made of more compliant materials has become increasingly popular for spine fusion surgery in recent years. The aim of this study was to compare stress responses of the implants in transforaminal lumbar interbody fusion (TLIF) when using flexible and conventional rigid posterior fixation systems. A previously validated intact L1-S1 finite element model was modified to simulate single-level (L4-L5) TLIF with bilateral pedicle screw fixation using two types of connecting rod (rigid and flexible rods). The von Mises stresses in the implants (including TLIF cage, pedicle screws and rods) for the rigid and flexible fixations were analyzed under static and vibration loadings. The results showed that compared with the rigid fixation, the use of flexible fixation decreased the maximum stress in the pedicle screws, but increased the maximum stress in the cage and the ratio of maximum stress in the rods to the yield stress. It was also found that with decreasing diameter of the flexible rod (i.e. increasing flexibility of the rod), the maximum stress was decreased in the pedicle screws but increased in the cage and the rods. The findings imply that compared with the rigid rod, application of the flexible rod in the pedicle screw fixation system for the TLIF might decrease the breakage risk of pedicle screws but increase the risk of cage subsidence and rod breakage. Moreover, flexibility of the rod in the flexible fixation system should be carefully determined.


Antinociceptive activity of the volatile oils of Hyptis pectinata L. Poit. (Lamiaceae) genotypes.
Hyptis pectinata L. Poit (Lamiaceae) is known popularly in Brazil as "sambacaita" or "canudinho" and is used in the treatment of inflammations, bacterial infections and ache. The antinociceptive activity of the volatile oils of six genotypes, at doses of 100, 200 and 400mg/kg body wt., were investigated using abdominal writhe models induced by acetic acid and hot plate tests. The volatile oils of all the genotypes are composed mainly of sesquiterpenoids. All the genotypes showed antinociceptive effects in both models used; the SAM002 genotype showed the major inhibitory effect at dose of 100mg/kg body wt. These results suggest that the volatile oil of H. pectinata has peripheral (writhe reduction) and central (time delay of thermal reaction) effects. These observations indicate that H. pectinata may be useful as an analgesic drug.


Promotive effect of macrophage colony-stimulating factor on long-term engraftment of murine hematopoietic stem cells.
Large ex vivo expansion of hematopoietic stem cells (HSCs) sufficient for use in clinical applications has not been achieved, although the influence of some cytokines including SCF, IL-11, Flt3-L, and TPO for this purpose has been reported. We present evidence for an indirect effect of macrophage colony-stimulating factor (M-CSF) on expansion of murine HSCs. Fresh Lin(-/low) cells were isolated from Ly5.1 mouse bone marrow and cultured with or without M-CSF in the presence of SCF + IL-11 + Flt3-L or SCF + IL-11 + TPO for 6 days. The expanded cells were harvested and transplanted into lethally irradiated Ly5.2 recipients with competitor cells. Culture of Lin(-/low) cells with M-CSF significantly enhanced long-term engraftment. When the more enriched HSC populations of Lin(-/low) c-Kit(+) Sca-1(+) cells were used as a source of HSCs, such a promotive effect was not observed, in agreement with negative expression of the M-CSF receptor (c-Fms). However, co-culture with Lin(-/low) c-Fms(+) resulted in a significant increase of long-term engraftment. These results suggested that M-CSF is an indirect stimulator for ex vivo expansion of HSCs in the presence of SCF, IL-11, Flt3-L, and TPO. These observations provide new directions for ex vivo expansion and insight into new engraftment regulation through M-CSF signaling.


[A case of bilateral acoustic neuroma in a 19-year-old girl].
A rare case of bilateral neurinoma of the acoustic nerve is described. The patient was a girl aged 19 years without external evidence of von Recklingshausen disease.


Effects of microplastics on distribution of antibiotic resistance genes in recirculating aquaculture system.
Microplastics and antibiotic resistance genes (ARGs) are two kinds of emerging contaminants with frequent detection in coastal regions. However, rare information on co-occurrence of microplastics and ARGs in coastal recirculating aquaculture system (RAS) is available. This study performed field sampling and laboratory analysis to investigate the distribution of microplastics and ARGs in a typical RAS farm. The results showed that microplastics were detected in all water samples with the abundances ranging from 58 to 72 items/m3. Absolute abundances of total 10 ARGs in water samples ranged from 3.24 × 105 to 7.83 × 105 copies/mL while those on microplastic samples were in the range of 1.59 × 109-1.83 × 109 copies/g. Microbial communities of microplastics and water showed significant difference at both phylum and genus levels. Microbial community diversity of microplastics was higher than that of water. ARGs including tetG, qnrS, sul1, sul2, and ermF possessed relatively more active relationships with bacterial community in water and on microplastics of the RAS farm. The results suggested that microplastics might be an important reservoir of ARGs in RAS farms. The findings of this study will provide useful information on pollution control and environmental management for both microplastics and ARGs in coastal aquaculture systems.


Unveiling the knowledge domain and emerging trends of olfactory dysfunction with depression or anxiety: A bibliometrics study.
Olfactory dysfunction (OD) accompanied by depression or anxiety is a very common clinical problem, and there has been a growing number of studies on OD with depression or anxiety in recent decades. This study performed bibliometric and visual analyses of the literature on OD with depression or anxiety to derive research trends and identify emerging research foci. Relevant publications were obtained from the Science Citation Index-Expanded and Social Sciences Citation Index in the Web of Science Core Collection databases (2002-2021). CiteSpace and VOSviewer were applied to identify and evaluate research foci and emerging trends in this research domain. The analyses found that the number of publications related to OD with depression or anxiety has increased significantly over the past 20 years, up from 15 in 2002 to 114 in 2022. The country that ranked highest in the number of articles and international cooperation was the United States. The top 10 most frequent keywords were "depression," "olfaction," "anxiety," "dysfunction," "olfactory bulbectomy," "olfactory dysfunction," "Parkinson's disease," "odor identification," "brain," and "disorders." Analysis of keywords with the strongest citation bursts revealed that "oxidative stress" is an emerging research hotspot. A timeline chart of the cluster of co-cited references demonstrated that Parkinson's disease was always a topic of interest in this area of research. This study conducted an objective, comprehensive, and systematic analysis of these publications, and identified the development of trends and hotspots in this research domain. It is hoped that this work will provide scholars, worldwide, with information to assist them in further research and the development of new therapies.


AngioJet rheolytic thrombectomy for the treatment of deep vein thrombosis in elderly patients: Increase the risk of acute kidney injury?
The objective of this study was to investigate the risk of acute kidney injury in elderly patients compared with nonelderly patients undergoing AngioJet rheolytic thrombectomy for treatment of acute deep vein thrombosis. A retrospective review of all patients who underwent AngioJet rheolytic thrombectomy for the treatment of acute deep vein thrombosis between November 1, 2014 and August 1, 2022 was conducted. Their baseline demographics, comorbidities, clinical characteristics, procedural details, and postoperative course were reviewed. A total of 105 eligible patients were reviewed; 45 patients were in the elderly group, and 60 were in the nonelderly group. Except for age (p < 0.001), no significant differences regarding demographics were detected (p >0.05). Transient macroscopic hemoglobinuria occurred in all patients during the first 24 h post-AngioJet rheolytic thrombectomy. The overall morbidity of acute kidney injury in the two groups was 11.4%, and the nonelderly group had a similar rate of acute kidney injury (8.3%) to the elderly group (15.6%). None of the 12 patients progressed to dialysis within the postoperative period, and the mean acute kidney injury recovery time of the elderly group was 5.86 ± 1.57 days, which was longer than the 3.60 ± .89 days of the nonelderly group (p = 0.017). The use of AngioJet rheolytic thrombectomy for the treatment of patients with acute deep vein thrombosis is associated with a potential risk of acute kidney injury, which seems to have a comparable rate in elderly and nonelderly patients. acute kidney injury in the elderly group tends to need a longer recovery time, which requires postoperative vigilance for this population.


Nipple sparing mastectomy: an innovative skin incision for an alternative approach.
Choice of the most appropriate surgical treatment for breast cancer patients can also be a technical issue. Cosmetic results after conservative surgery can be poor in certain instances and, at the same time, total mastectomy can appear as an over-treatment. For some selected patients, the "nipple sparing mastectomy" (NSM) is an alternative surgical treatment and more and more papers on this technique are appearing in the literature. One hundred and two NSMs have been performed in our department between June 2003 and October 2006, initially via periareolar skin incision, now through a skin incision on the lateral aspect of the breast to reduce the necrotic risk for the nipple. The lateral skin incision saves the integrity of skin blood supply, allows for a complete breast gland removal and saves the integrity of the body image of women who show no scars when seen upfront.


Facing Southern Ocean warming: Temperature effects on whole animal performance of Antarctic krill (Euphausia superba).
The ongoing environmental changes in the Southern Ocean may cause a dramatic decrease in habitat quality. Due to its central position in the food web, Antarctic krill (Euphausia superba) is a key species of the marine Antarctic ecosystem. It is therefore crucial to understand how increasing water temperatures affect important krill life-cycle processes. Here, a long-term (August - March) laboratory acclimation experiment at different temperature scenarios (0.5 °C, 1.5 °C, 2.5 °C, 3.5 °C, 5 °C, 7 °C) was performed and the effects of elevated temperatures on whole animal parameters (O2 consumption, body length, length of the digestive gland) were analyzed. The response of krill oxygen consumption to different experimental temperatures differed between acute/short-term and long-term acclimation. After 8 months, krill oxygen consumption remained unchanged up to temperatures of 3.5 °C and was significantly higher at temperatures > 3.5 °C. Krill acclimated to temperatures ≥ 3.5 °C were significantly smaller at the end of the experiment. Limited food intake and/or conversion may have contributed to this effect, especially pronounced after the onset of the reproductive period. In addition, the seasonal growth pattern in males differed from that of females. Together, our findings indicate that warming Southern Ocean waters are likely to increase metabolic rate in krill, possibly altering the amount of energy available for other important life-cycle processes, a finding directly related to future population dynamics and fisheries management.


Maize plant (Zea mays) uptake of organophosphorus and novel brominated flame retardants from hydroponic cultures.
The root uptake and root-shoot translocation of seven organophosphorus flame retardants (OPFRs) and four novel brominated flame retardants (NBFRs) were assessed in this investigation using hydroponic grown maize plants (Zea mays). Three initial liquid concentrations for each considered compound were examined (i.e., 0.3 μg L-1, 3 μg L-1, 30 μg L-1). The results indicated that the 30 μg L-1 treatments were phytotoxic, as they resulted in a significant decrease in shoot dry weight. Plant-driven removal of the tested FRs decreased with the increasing initial spiking level and were reportedly higher for the NBFRs (range 42%-10%) than OPFRs (range 19%-7%). All the considered FRs were measured in the roots (range 0.020-6.123 μg g-1 dry weight -DW-) and shoots (range 0.012-1.364 μg g-1 DW) of the tested plants, confirming that there was uptake. Linear relationships were identified between the chemical concentrations in the plant parts and the tested hydroponic concentrations. Root concentration factors were positively correlated with the specific lipophilicity (i.e., logKow) of the tested FRs and were determined to be higher for the NBFRs than the OPFRs. The NBFRs had a higher root uptake rate than the OPFRs, and this trend was more significant with the increasing treatment concentrations. Shoot/root concentration factors were found to be lower than the unity value for 10 of the 11 tested compounds. These results can be related to the specific molecular configurations and the occurrence of different functional groups in the tested compounds. The results will help to improve risk assessment procedures and fine tune our understanding of human receptor responses to the ingestion of maize crops grown on agricultural sites irrigated with water contaminated by FRs.


Association of exposure to ambient air pollution with ovarian reserve among women in Shanxi province of north China.
Air pollution has been an important risk factor for female reproductive health. However, epidemiological evidence of ambient air pollution on the predictor for ovarian reserve (antral follicle count, AFC) is deficient. We aim to comprehensively evaluate the association of long-term exposure to ambient air pollution with AFC among women of reproductive age in Shanxi of north China. 600 women with spontaneous menstrual cycle, not using controlled ovarian stimulation, were enrolled in the retrospective study. Two distinct periods of antral follicle development were designed as exposure windows. Generalized linear model was employed to estimate the change of AFC associated with exposure of atmospheric pollutants (SO2, NO2, PM10, PM2.5, CO and O3). Stratification analysis based on age (<30, ≥30 years), university degree (yes, no), years of exposure (2013-2016, 2017-2019) and duration of infertility (<2, 2-5, >5 years) along with two pollutants model were employed to further illustrate the association. We found every 10 μg/m3 increase in SO2 concentration level during the entire development stage of antral follicle was associated with a -0.01 change in AFC (95% confidence interval: -0.016, -0.002) adjusting for the confounders including age, BMI, parity and infertility diagnosis factors. The significant association of increased SO2 level with decreased AFC was particularly observed during the early transition from primary follicle to preantral follicle stage by 10 μg/m3 increase in SO2 exposure level with a -0.01 change (95% CI: -0.015, -0.002) in AFC. The negative association was pronounced among women aged ≥30 years old, and also significant in two pollutants model after adjusting the confounders. No significant associations between other air pollutants and AFC were observed. Our finding suggests that long-term exposure to air pollutant SO2 is associated with lower AFC, raising our concern that atmospheric SO2 exposure may have potential adverse impact on women ovarian reserve.


Copper(II) dinuclear pyrazine-based rack-type complexes: preparation, structure, and magnetic properties.
A novel class of ditopic ligands, 1, was synthesized by the reaction of 2,5-pyrazine-dicarboxaldehyde with 2 equiv of acyl-/aroyl-hydrazine. Their structures were confirmed by 1D and 2D NMR and by X-ray crystallography. They gave heteroleptic Cu(II) dinuclear rack-like complexes of the formula [Cu(2)1(terpy)(2)](OTf)(4), thus undergoing shape changes of significant amplitude. The solid-state structures of these complexes were determined by X-ray crystallography. The magnetic measurements performed on the complexes revealed the presence of antiferromagnetic intramolecular interactions.


Tracking the diversity and interaction of methanogens in the energy recovery process of a full-scale wastewater treatment plant.
Methanogens have been significant for the achievement of carbon neutrality in wastewater treatment plants due to their crucial roles in the anaerobic digestion of sludge. Nevertheless, the phylogenetic diversity of methanogens and their versatile metabolism have been continuously investigated, the current scientific knowledge regarding these microbes appears inadequate and requires more evaluations. This study is considered an endeavor in which functional genes sequencing was used to reveal the diversity of methanogens in the sludge process of the wastewater treatment plant. The information obtained was substantially more than that employing 16s sequencing. The methanogenic microbial resources were appropriate to sustain a self-inoculated energy recovery with a potential ability to boost methane production. A constancy was observed in 16 S rRNA gene and mcrA gene sequencing results, where the bacterial or Methanosaeta concilii dominated community of DS (digest sludge) was distinct from the inoculum sources TS (total sludge), CTS (concentrated total sludge), and HTS (hydrolysis total sludge), indicating the independent development of DS. A quantitative cross-network was constructed by coupling the absolute quantify of 16 S rRNA and mcrA sequences. The Methanobacterium petrolearium actively interacted with bacteria in the DS community rather than the dominant species (Methanosaeta concilii). Moreover, the unclassified methanogens were identified to be significantly prevalent in all communities, suggesting that unknown methanogenic taxa might be imperative in accomplishing community functions. Collectively, the findings of this research study will shed light on the comprehensive knowledge of microbial communities, especially the methanogenic microbiota. This will further enhance the exploration of the phylogenetic diversity of methanogens and their corresponding impacts in energy recovery from wastewater treatment plants.


Failure of salicylate to reduce inhibition of human venous prostacyclin in synthesis by conventional dose aspirin.
Ex vivo venous prostacyclin synthesis was measured in 24 patients who received no medication, or a single oral dose of aspirin 300 mg, sodium salicylate, 500 mg, or a combination of sodium salicylate 500 mg followed by aspirin 300 mg 1 1/2 or 3 hr later. Aspirin alone substantially reduced PGI2 synthesis but sodium salicylate alone had no effect. Sodium salicylate administration prior to aspirin did not reverse the inhibitory effect of aspirin on PGI2 synthesis.


Differential activation of cytotoxic responses by Burkitt's lymphoma (BL)-cell lines: relationship to the BL-cell surface phenotype.
Epstein-Barr (EB) virus-positive Burkitt's lymphoma (BL) cell lines, recently established from tumour biopsies and displaying chromosomal translocations indicative of their malignant origin, can be classified into two broad sets: (i) lines growing predominantly as single cells/small clumps whose cell surface markers remain close to those of the original tumour cells, and (ii) lines whose growth pattern and cell surface markers have progressed closer to the more "lymphoblastoid" phenotype displayed by all in vitro transformed B-cell lines (LCLs) of normal origin. When compared to LCLs derived from normal B cells of the same patient, BL-cell lines in set (i) generally showed a lower expression of HLA class I and class II antigens and a reduced ability to activate both allospecific and nonspecific (natural killer-like) cytotoxic responses when cocultured with peripheral blood lymphocytes. By contrast, the HLA antigen expression and in vitro stimulatory capacity of most BL-cell lines in set (ii) were much closer to the values displayed by their corresponding LCLs. Since set (i) rather than set (ii) BL cell lines are phenotypically representative of the malignant cells as they exist in vivo, this work suggests that successful outgrowth of the virus-carrying tumour cells in the affected host may be facilitated by the inability of these cells to stimulate strong cytotoxic responses.


Study on surface enhanced Raman scattering of Au and Au@Al2O3 spherical dimers based on 3D finite element method.
In this paper, the surface enhanced Raman scattering (SERS) characteristics of Au and Au@Al2O3 nanoparticle dimers were calculated and analyzed by using finite element method (3D-FEM). Firstly, the electric field enhancement factors of Au nanoparticles at the dimer gap were optimized from three aspects: the incident angle of the incident light, the radius of nanoparticle and the distance of the dimer. Then, aluminum oxide is wrapped on the Au dimer. What is different from the previous simulation is that Al2O3 shell and Au core are regarded as a whole and the total radius of Au@Al2O3 dimer is controlled to remain unchanged. By comparing the distance of Au nucleus between Au and Au@Al2O3 dimer, it is found that the electric field enhancement factor of Au@Al2O3 dimer is much greater than that of Au dimer with the increase of Al2O3 thickness. The peak of electric field of Au@Al2O3 dimer moves towards the middle of the resonance peak of the two materials, and it is more concentrated than that of the Au dimer. The maximum electric field enhancement factor 583 is reached at the shell thickness of 1 nm. Our results provide a theoretical reference for the design of SERS substrate and the extension of the research scope.