Changes in the lipid composition of ripening banana fruits and evidence for an associated increase in cell membrane permeability.
The content of total lipid in banana fruit pulp tissue remained constant during the climacteric rise induced by applied ethylene. The relative proportions of neutral lipid, glycolipid and phospholipid did not change. However, the fatty acid composition of the lipid did change during ripening. This change was confined largely to the phospholipid fraction, in which there was an increase in the proportion of linolenic acid and a decrease in the proportion of linoleic acid. The net result was an increase in total unsaturation of the fatty acids in the phospholipid fraction. Measurements of spin label motion in liposomes prepared from banana phospholipids showed that the motion and fluidity of bilayer lipids increased during ripening of the fruit from which the liposomes were prepared, probably as a result of increased lipid unsaturation during ripening. Since increases in membrane fluidity are accompanied by increases in the passive permeability to small molecules in a number of membrane systems, it is suggested that the increased leakage which has been previously demonstrated in ripening banana fruit tissue is due to increases in the permeability of at least some cell membranes.


Relative androgenicity, blood pressure levels, and cardiovascular risk factors in young healthy women.
To test the hypothesis that androgens may play a role in the pathogenesis of atherosclerosis and hypertension, we investigated the association of delta 5 dehydroepiandrosterone sulfate [DHEAS]) and delta 4 (free testosterone [FT]) androgens with the resting, seated blood pressure (BP) levels and cardiovascular risk factors in 280 young, healthy women 18 to 24 years of age. After application of multiple regression analysis, systolic BP was positively and independently correlated with the ratio of dehydroepiandrosterone sulfate to free testosterone (DHEAS/FT), fasting insulin levels, and the diastolic BP with DHEAS/FT only. The DHEAS/FT ratio proved to be a stronger predictor of the BP levels than either hormone alone. Further, uric acid concentrations and HDL/total cholesterol ratio were independently correlated with both FT and body mass index in these young women. Serum triglycerides were independently correlated with FT and central body fat distribution. These data suggest that serum androgen concentrations are important independent predictors of cardiovascular risk factors and that the ratio of dehydroepiandrosterone sulfate to free testosterone ratio is an independent predictor of blood pressure levels in young women.


[Simultaneous occurrence of arteriosclerosis obliterans and venous diseases].
It is reported on the pathophysiological peculiarities which may appear in the coincidence of the two vascular diseases. As therapy the fibrinolysis with Awelysin should always be taken into consideration.


Histologic hypercellularity in a biopsied normal parathyroid gland does not correlate with hyperfunction in primary hyperparathyroidism.
About 15% of patients with primary hyperparathyroidism have multiglandular disease, thus during resection of an apparent single adenoma, a visibly normal parathyroid may be identified and biopsied. Using long-term biochemical follow-up, we examined whether normal parathyroid hypercellularity correlates with multiglandular disease or primary hyperparathyroidism recurrence. We reviewed all patients who from 2001 to 2015 had an initial operation for sporadic primary hyperparathyroidism with removal of 1 gland, routine normal parathyroid biopsy, intraoperative parathyroid hormone monitoring, and follow-up of ≥3 years. Recurrence was defined by hypercalcemia after documented cure at 6 months, and hypercellularity by standard histologic criteria. Of 134 patients with mean follow-up of 9.4 years (range, 3.1-15.9), 132 (98.5%) exhibited cure at 6 months. Two had initial failure, and 8 of 132 (6.1%) developed recurrent hyperparathyroidism (mean 5.8 y, range 4-10.6). The normal parathyroid was hypercellular in 14 of 132 (10.6%) of the cured patients, and this rate did not differ for those with long-term cure (12/124, 9.7%) versus recurrence (2/8, 25%, P = .2). The positive predictive value of normal parathyroid hypercellularity for recurrence was low (14.3%), and the negative predictive value of normal parathyroid normocellularity was high (94.9%). During the initial operation for primary hyperparathyroidism, 10% of normal parathyroids are hypercellular, but this does not signify missed multiglandular disease. In contrast, normal parathyroid normocellularity has high predictive value for durable cure (95%), slightly better than visual identification of a second normal parathyroid (94%).


Circular RNA circANKRD36 regulates Casz1 by targeting miR-599 to prevent osteoarthritis chondrocyte apoptosis and inflammation.
Osteoarthritis (OA) is an ageing-related disease characterized by articular cartilage degradation and joint inflammation. circRNA has been known to involve in the regulation of multiple inflammatory diseases including OA. However, the mechanism underlying how circRNA regulates OA remains to be elucidated. Here, we report circANKRD36 prevents OA chondrocyte apoptosis and inflammation by targeting miR-599, which specifically degrades Casz1. We performed circRNA sequencing in normal and OA tissues and found the expression of circANKRD36 is decreased in OA tissues. circANKRD36 is also reduced in IL-1β-treated human chondrocytes. FACS analysis and Western blot showed that the knockdown of circANKRD36 promotes the apoptosis and inflammation of chondrocytes in IL-1β stress. We then found miR-599 to be the target of circANKRD36 and correlate well with circANKRD36 both in vitro and in vivo. By database analysis and luciferase assay, Casz1 was found to be the direct target of miR-599. Casz1 helps to prevent apoptosis and inflammation of chondrocytes in response to IL-1β. In conclusion, our results proved circANKRD36 sponge miR-599 to up-regulate the expression of Casz1 and thus prevent apoptosis and inflammation in OA.


Targeting the Divergent Roles of STK3 Inhibits Breast Cancer Cell Growth and Opposes Doxorubicin-Induced Cardiotoxicity In Vitro.
Breast cancer (BCa) is the most prevalent type of cancer in women. Several therapies used in the treatment of breast cancer are associated with clinically important rates of cardiovascular toxicity during or after treatment exposure, including anthracyclines. There is a need for new BCa therapeutics and treatments that mitigate chemotherapy-induced cardiotoxicity in BCa. In this study, we examine the effects of Serine/Threonine Kinase 3 (STK3) inhibition in the context of BCa therapy and cardioprotection from doxorubicin. STK3 (also known as MST2) is a key member of the Hippo Tumor-Suppressor Pathway, which regulates cell growth and proliferation by inhibiting YAP/TAZ co-transcription factors. Canonically, STK3 should restrict BCa growth; however, we observed that STK3 is amplified in BCa and associated with worse patient outcomes, suggesting a noncanonical pro-tumorigenic role. We found BCa cell lines have varying dependence on STK3. SUM52PE cells had the highest expression and dependence on STK3 in genetic and pharmacological assays. MCF-7 and MDA-MB-231 were less sensitive to STK3 targeting in standard proliferation assays, but were STK3 dependent in colony formation and matrigel invasion assays. In contrast, STK3 inhibition mitigated the toxic effects of doxorubicin in H9C2 rat cardiomyocytes by increasing YAP expression. Importantly, STK3 inhibition in BCa cells did not interfere with the therapeutic effects of doxorubicin. Our studies highlight STK3 is a potential molecular target for BCa with dual therapeutic effects: suppression of BCa growth and progression, and chemoprotection in cardiomyocytes.


Patients with glycogen storage diseases undergoing anesthesia: a case series.
Glycogen storage diseases are rare genetic disorders of glycogen synthesis, degradation, or metabolism regulation. When these patients are subjected to anesthesia, perioperative complications can develop, including hypoglycemia, rhabdomyolysis, myoglobinuria, acute renal failure, and postoperative fatigue. The objective of this study was to describe the perioperative course of a cohort of patients with glycogen storage diseases. This is a retrospective review of patients with glycogen storage diseases undergoing anesthetic care at our institution from January 1, 1990, through June 30, 2015 to assess perioperative management and outcomes. We identified 30 patients with a glycogen storage disease who underwent 41 procedures under anesthesia management. Intraoperative lactic acidosis developed during 4 major surgeries (3 liver transplants, 1 myectomy), and in all cases resolved within 24 postoperative hours. Lactated Ringer solution was used frequently. Preoperative and intraoperative hypoglycemia was noted in some patients with glycogen storage disease type I, all of which responded to administration of dextrose-containing solutions. No serious postoperative complications occurred. Patients with glycogen storage disease, despite substantial comorbid conditions, tolerates the anesthetic management without major complications. Several patients who experienced self-limited metabolic acidosis were undergoing major surgical procedures, during which acidosis could be anticipated. Close monitoring and management of blood glucose levels of patients with glycogen storage disease type I is prudent.


Radionuclide tracing of water masses and processes in the water column and sediment in the Algerian Basin.
Caesium-137 and (239,240)PU were analysed in the water column along the Algerian coast. The (137)Cs activity concentration in surface water increased from the west to the east from 1.6 to 3.3 mBq L(-1), documenting a presence of Modified Atlantic Water (MAW) in the region. Higher concentrations observed in deep waters may be due to an intrusion of Levantine Intermediate Water (LIW), which has been carrying higher levels of (137)Cs from Chernobyl accident. The (239,240)Pu sub-surface concentration peaked at about 250 m water depth as a result of biogeochemical processes in the water column. The observed (239,240)Pu/(137)Cs activity ratio at the surface (0.003) was significantly lower than that in global fallout (0.04). This decrease exceeds that expected from radioactive decay of (137)Cs, and confirms that Pu due to its adsorption on sinking particles is more effectively removed from surface layers than is (137)Cs. An increase of the (239,240)Pu/(137)Cs activity ratio with depth suggests that (239,240)Pu, similarly as (137)Cs, should be also transported by advection to maintain the observed ratios in deep waters. An intrusion of LIW may enhance therefore both the (137)Cs and (239,240)Pu concentrations in deep waters. The average (238)Pu/(239+240)Pu activity ratio in seawater was 0.03+/-0.02, confirming a global fallout origin of Pu in the Algerian Basin. Caesium-137 and (239,240)Pu inventories in the water column were estimated to be from 2.7+/-0.5 kBq m(-2) to 3.8+/-0.7 kBq m(-2), and from 13.8+/-2.6 Bq m(-2) to 41+/-7B qm(-2), respectively. The (137)Cs massic activities in surface sediment were almost constant, the average activity was 9.0+/-0.8 Bq kg(-1). Sedimentation rates obtained using the (210)Pb method were from 0.1 to 0.7 cm y(-1), and resulting penetration depths of (137)Cs in the sediment cores were from 15 to over 40 cm. The (137)Cs peaks found in the sediment cores were associated with the Chernobyl accident (1986) and global fallout (1964). The (137)Cs inventories in the sediment were increasing from the west (180 Bq m(-2)) to the east (350 Bq m(-2)).


Efficacy and Safety of Sofosbuvir-based Regimens in Hepatitis C Patients With Decompensated Cirrhosis: A Systematic Review and Meta-analysis.
Decompensated cirrhotic patients with hepatitis C (HCV) are often under-represented in clinical trials. We aimed to evaluate pooled data on the efficacy and safety of sofosbuvir (SOF)-based regimens in these patients. We conducted a systemic review and meta-analysis by searching multiple databases for studies published from October 2010 to October 2020. Outcomes of interest were sustained virologic response (SVR) and safety of SOF-based regimens in decompensated HCV patients. Two reviewers independently performed the study selection and data extraction. We included 33 studies that enrolled 5,302 HCV patients. The pooled SVR rate in decompensated patients with SOF-based regimens was 85.1% (95% CI: 82.8-87.3). Patients on SOF/velpatasvir±ribavirin achieved a significantly higher SVR (91.0%, 95% CI: 87.7-93.9) than that of SOF/ledipasvir±ribavirin [(86.3%, 95% CI: 84.6-87.8); p=0.004)], or on SOF/daclatasvir±ribavirin (82.4%, 95% CI: 78.2-86.2%; p<0.001). Adding ribavirin to SOF-based regimens (pooled SVR 84.9%, 95% CI: 81.7-87.9) did not significantly increase the SVR [(83.8% (95% CI: 76.8-89.8%; p=0.76)] in decompensated patients, which was also true in subgroup analyses for each regimen within the same treatment duration. However, adding ribavirin significantly increased the frequency of adverse events from 52.9% (95% CI: 28.0-77.1) to 89.2% (95% CI: 68.1-99.9) and frequency of severe events. The pooled incidence of hepatocellular carcinoma and case-fatality of decompensated patients were 3.1% (95% CI: 1.5-5.0) and 4.6% (95% CI: 3.1-6.3), respectively. The overall heterogeneity was high. There was no publication bias. The analysis found that 12 weeks of SOF/velpatasvir without ribavirin is the preferred therapy, with a significantly higher SVR compared with other SOF-based regimens in decompensated HCV patients.


An investigation of the flexion relaxation ratio in adults with and without a history of self-reported low back pain and transient sitting-induced pain.
It is unknown whether the presence of sitting-induced pain or a clinical history of low back pain (LBP) changes spine function outcomes such as the flexion relaxation ratio (FRR). The purpose of this investigation was to determine whether sitting-induced pain or a history of non-specific LBP results in a different FRR. Forty-seven participants were instrumented with surface electromyography over erector spinae at L1, and accelerometers at L1 and S2. Standing maximum lumbar flexion trials were taken preceding and following a 1-hour sitting trial. Pain ratings during sitting and history of LBP were used to group participants for analysis. FRR values taken after the sitting exposures were compared between those that did and did not develop pain during sitting. Baseline FRR values were compared participants with and without a history of LBP. No significant differences in FRR were found for either pain groups (p = 0.11) or clinical history (p = 0.85). Lack of differences may be due to participants not currently experiencing a clinical episode of pain when the ratio was measured and/or because 1-hour sitting exposure was not long enough to induce pain modulation. The findings suggest that neither sitting-induced pain development or clinical history need to be controlled to prevent confounding of FRR.


[Mechanical kidney injury what urologists miss in medical records].
The article provides a brief description of the main terms and concepts of kidney damage used in forensic medicine and urology, with a list of requirements for the description and formation of a clinical diagnosis when maintaining primary medical documentation. The importance of a unified approach in objective interpretation in the expert assessment of kidney injuries is substantiated.


Target-independent hybridization chain reaction-fluorescence resonance energy transfer for sensitive assay of ctDNA based on Cas12a.
Circulating tumor DNA (ctDNA) is a noninvasive biomarker which offer valuable information for cancer diagnosis and prognosis. In this study, a target-independent fluorescent signal system, Hybridization chain reaction-Fluorescence resonance energy transfer (HCR-FRET) system, is designed and optimized. Combined with CRISPR/Cas12a system, a fluorescent biosensing protocol was developed for sensing assay of T790 M. When the target is absent, the initiator remains intact, opens the fuel hairpins and triggers the following HCR-FRET. At presence of the target, the Cas12a/crRNA binary complex specifically recognizes the target, and the Cas12a trans-cleavage activity is activated. As a result, the initiator is cleaved and subsequent HCR responses and FRET processes are attenuated. This method showed detection range from 1 pM to 400 pM with a detection limit of 316 fM. The target independent property of the HCR-FRET system endows this protocol a promising potential to transplant to the assay of other DNA target in parallel.


An adaptive Tikhonov regularization method for fluorescence molecular tomography.
The high degree of absorption and scattering of photons propagating through biological tissues makes fluorescence molecular tomography (FMT) reconstruction a severe ill-posed problem and the reconstructed result is susceptible to noise in the measurements. To obtain a reasonable solution, Tikhonov regularization (TR) is generally employed to solve the inverse problem of FMT. However, with a fixed regularization parameter, the Tikhonov solutions suffer from low resolution. In this work, an adaptive Tikhonov regularization (ATR) method is presented. Considering that large regularization parameters can smoothen the solution with low spatial resolution, while small regularization parameters can sharpen the solution with high level of noise, the ATR method adaptively updates the spatially varying regularization parameters during the iteration process and uses them to penalize the solutions. The ATR method can adequately sharpen the feasible region with fluorescent probes and smoothen the region without fluorescent probes resorting to no complementary priori information. Phantom experiments are performed to verify the feasibility of the proposed method. The results demonstrate that the proposed method can improve the spatial resolution and reduce the noise of FMT reconstruction at the same time.


Limited suppression of prostate-specific antigen after salvage radiotherapy for its isolated elevation after radical prostatectomy.
To investigate the clinical outcome and degree of prostate-specific antigen (PSA) suppression after salvage radiotherapy performed because of isolated PSA elevation after radical prostatectomy. We examined the outcomes of 32 patients who underwent radiotherapy after radical prostatectomy. Hypersensitive, as well as conventional, PSA assays were used to measure PSA levels after irradiation. Of 125 patients who underwent radical prostatectomy for clinically resectable prostate cancer, 42 (33.6%) developed detectable PSA an average of 13.5 months postoperatively. Thirty-two patients underwent salvage radiotherapy. In 13 patients (40.6%), PSA became undetectable (less than 0.1 ng/mL) at a mean of 1.2 months. Two of these patients later developed detectable PSA within 1 2 months. Of 22 patients who had at least 12 months of follow-up, 8 had a durable PSA response. Of 13 patients who attained an undetectable PSA postoperatively and then showed a delayed progressive increase, 7 exhibited a durable response lasting for more than the 12 months after irradiation. By contrast, only 1 of 9 patients with persistently elevated postoperative PSA showed undetectable levels after irradiation. Frozen sera from the 8 patients with a durable response to irradiation were available to measure levels less than 0.1 ng/mL by hypersensitive assay. The mean value was 0.035 ng/mL at an average of 26.9 months after irradiation. Only 3 patients had levels less than 0.01 ng/mL. Although radiotherapy may be beneficial in a small number of patients, many patients continue to have measurable levels of PSA (more than 0.01 ng/mL) after irradiation. Our results suggest that this treatment in its current form is inadequate to eradicate residual carcinoma.


Effect of hypobaric hypoxia on the fiber type transition of skeletal muscle: a synergistic therapy of exercise preconditioning with a nanocurcumin formulation.
Hypobaric hypoxia (HH) leads to various adverse effects on skeletal muscles, including atrophy and reduced oxidative work capacity. However, the effects of HH on muscle fatigue resistance and myofiber remodeling are largely unexplored. Therefore, the present study aimed to explore the impact of HH on slow-oxidative fibers and to evaluate the ameliorative potential of exercise preconditioning and nanocurcumin formulation on muscle anti-fatigue ability. C2C12 cells (murine myoblasts) were used to assess the effect of hypoxia (0.5%, 24 h) with and without the nanocurcumin formulation (NCF) on myofiber phenotypic conversion. To further validate this hypothesis, male Sprague Dawley rats were exposed to a simulated HH (7620 m) for 7 days, along with NCF administration and/or exercise training. Both in vitro and in vivo studies revealed a significant reduction in slow-oxidative fibers (p < 0.01, 61% vs. normoxia control) under hypoxia. There was also a marked decrease in exhaustion time (p < 0.01, 65% vs. normoxia) in hypoxia control rats, indicating a reduced work capacity. Exercise preconditioning along with NCF supplementation significantly increased the slow-oxidative fiber proportion and exhaustion time while maintaining mitochondrial homeostasis. These findings suggest that HH leads to an increased transition of slow-oxidative fibers to fast glycolytic fibers and increased muscular fatigue. Administration of NCF in combination with exercise preconditioning restored this myofiber remodeling and improved muscle anti-fatigue ability.


Radiology-pathology conference: primary adrenal lymphoma.
We present a case of a 62-year-old man with a history of type II diabetes mellitus who presented to our emergency department with back pain and right upper quadrant abdominal pain associated with vomiting and weight loss. A computed tomographic scan of the abdomen and pelvis demonstrated a large adrenal mass, and subsequent biopsy showed primary adrenal lymphoma.


Association between Metabolic Syndrome and Cognitive Impairment after Acute Ischemic Stroke: A Cross-Sectional Study in a Chinese Population.
Metabolic syndrome (MetS), a risk factor for many vascular conditions, is associated with vascular cognitive disorders. The objective of the present study was to explore the associations of MetS and its individual components with the risks of cognitive impairment and neurological dysfunction in patients after acute stroke. This cross-sectional study enrolled 840 patients ranging in age from 53 to 89 years from the Tianjin area of North China. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination. Neuropsychiatric behavior was assessed using the Neuropsychiatric Inventory Questionnaire. Emotional state was examined according to the Hamilton Depression Rating Scale, and neuromotor function was evaluated using the National Institutes of Health Stroke Scale, Barthel index, and the Activity of Daily Living test. After overnight fasting, blood samples were obtained to measure biochemistry indicators. MetS and its individual components were closely correlated with MoCA score. MetS patients had high levels of inflammation and a 3.542-fold increased odds ratio (OR) for cognitive impairment [95% confidence interval (CI): 1.972-6.361]. Of the individual MetS components, central obesity (OR 3.039; 95% CI: 1.839-5.023), high fasting plasma glucose (OR 1.915; 95% CI: 1.016-3.607), and type 2 diabetes (OR 2.241; 95% CI: 1.630-3.081) were associated with an increased incidence of cognitive impairment. Consistent and significant worsening in different neurological domains was observed with greater numbers of MetS components. MetS was associated with worse cognitive function, neuromotor dysfunction, and neuropsychological symptoms among Chinese acute stroke patients.


Review on antioxidants and evaluation procedures.
Antioxidants are the substances that are capable of counteracting the damaging effects of the physiological process of oxidation occur in animal tissues. These may be nutrients (vitamins and minerals) as well as enzymes (proteins) in our body that assist in chemical reactions. They are believed to play a role in preventing the development of chronic diseases like cancer, diabetes, heart disease, stroke, Alzheimer's disease, rheumatoid arthritis, and cataracts etc. The present review article emphasizes on the various aspects of oxidants and antioxidants viz. definition, types, causes, mechanism, functions, adverse effects along with various in vivo and in vitro models of evaluation of antioxidant activity of new molecule, compounds or any plant or plant part. This review is one of its kinds which will be of great importance for researchers working in this area in search of antioxidant moieties and their biological evaluation.


Trachoma, flies and environmental factors in Burkina Faso.
The presence of flies is one of the earliest risk factors for trachoma and it has been suggested that flies could act as vectors for transmission of chlamydiae. A national trachoma survey was conducted in 1997 in Burkina Faso to (i) study the relationship between trachoma occurrence, flies, dirty faces and some environmental factors, and (ii) investigate the role of flies in the presence of trachoma. The country was stratified into eight groups of provinces and a random sample of 30 clusters was selected in each group. All children aged < 10 years were examined for the diagnosis of active trachoma (trachomatous inflammation which was follicular and/or intense) and the dirtiness of the face and the presence of flies on the face were recorded. The children's carers were questioned about the number of baths given and daily face-washing. Household heads were asked about ownership of cattle and small ruminants. The presence of latrines, a stable, and garbage collection inside the yard was noted. Among 16,514 children examined, 27.0% had active trachoma and 3.3% intense inflammatory trachoma. Flies were present on 11.2% of children's faces and 82.4% and 19.7% of these children had active and intense inflammatory trachoma, respectively. Among the 30.2% of children with dirty faces, 70.2% had active and 10.2% intense inflammatory trachoma. In multivariate analysis, at least one daily bath showed a protective effect on both active and intense inflammatory trachoma. Face-washing twice daily was found to be significantly protective for active trachoma in some regions. A strong association was demonstrated between the presence of flies and dirty faces (odds ratio = 334, 95% confidence interval 202-546). The presence of flies on children's faces, dirty faces and trachoma appeared to be strongly associated. Although the presence of flies may be a marker of socio-economic status and is probably linked with other trachoma risk factors, our data indicated that interventions targeting fly control should be an important issue in controlling trachoma.


A new technique to explant an infected aortic endograft.
The management of an infected aortic endograft can be challenging both operatively and clinically. Although aortic endograft infection is rare, the incidence is likely to increase in the coming years because of ever rising numbers of endovascular aneurysm repairs. Definitive management involves the removal of the endograft through laparotomy. Removal of the graft is technically challenging; no manufacturer's device is available to assist in disengagement of barbed hooks that hold the endograft in position. We present a new technique using the disposable proctoscope as a device to facilitate safe removal of the endograft with minimal damage to the aortic wall.


Mitochondrial mass of circulating NK cells as a novel biomarker in severe SARS-CoV-2 infection.
Severe SARS-CoV-2 infection results in lymphopenia and impaired function of T, B, and NK (TBNK-dominant) lymphocytes. Mitochondria are essential targets of SARS-CoV-2 and the efficacy of lymphocyte mitochondrial function for immunosurveillance in COVID-19 patients has not been evaluated. Multi-parametric flow cytometry was used to characterize mitochondrial function, including mitochondrial mass (MM) and low mitochondrial membrane potential (MMPlow), in TBNK-dominant lymphocytes from severe (n = 93) and moderate (n = 77) hospitalized COVID-19 patients. We compared the role of novel lymphocyte mitochondrial indicators and routine infection biomarkers as early predictors of severity and death in COVID-19 patients. We then developed a mortality decision tree prediction model based on immunosurveillance indicators through machine learning. At admission, the MM of circulating NK cells (NK-MM) was the best discriminator of severe/moderate disease (AUC = 0.8067) compared with the routine infection biomarkers. The NK cell count and NK-MM displayed superior diagnostic effects to distinguish patients with non-fatal or fatal outcomes. Interestingly, NK-MM was significantly polarized in non-survivors, with some patients showing a decrease and others showing an abnormal increase. Kaplan-Meier analysis showed that NK-MM had the optimal predictive efficacy (hazard ratio = 11.66). The decision tree model has the highest proportion of importance for NK-MM, which is superior to the single diagnostic effect of the above indicators (AUC = 0.8900). NK-MM was not only associated with disease severity, its abnormal increases or decreases also predicted mortality risk. The resulting decision tree prediction model is the first to focus on immune monitoring indicators to provide decision-making clues for COVID-19 clinical management.


Hemisphere-dependent cognitive performances in epileptic patients.
Short-term memory (STM), long-term memory (LTM), and recency judgment were investigated in 75 right-handed nonaphasic patients without visual deficits who had epileptic foci localized in one of four different regions of the brain: right temporal lobe, left temporal lobe, right frontal lobe, and left frontal lobe. The results led to the following conclusions: (1) left temporal lesions yielded comparatively greater impairment for the verbal LTM task, whereas right temporal lesions were more disruptive for the spatial LTM task; (2) no significant differences between left- and right-brain-damaged patients in STM tasks were obtained; (3) left frontal lesions yielded deficits in a recency task in accordance with hemispheric specialization; (4) only prolonged epileptic syndromes impaired neuropsychological performance in those tests; (5) comparisons between male and female patients and between those with and without clear evidence of a structural lesion did not reach statistical significance.


How well do published randomized controlled trials on pelvic floor muscle training interventions for urinary incontinence describe the details of the intervention? A review.
Pelvic floor muscle training (PFMT) is strongly recommended for the management of mild to moderate urinary incontinence (UI) in women, yet the specific elements of PFMT that lead to improvement have not been identified. This gap in knowledge may be related, at least in part, to the lack of detail provided on intervention parameters reported in randomized controlled trials (RCTs) OBJECTIVE: Using three different instruments: the Consensus on Exercise Reporting Template (CERT), the template for intervention description and replication (TIDieR) checklist, and the Consensus on Therapeutic Exercise Training (CONTENT) scale, the purpose of this study was to assess the completeness of exercise reporting among moderate to high quality RCTs on PFMT for women with UI. Two raters independently scored all 65 RCTs (n = 65) retrieved by the most up-to-date Cochrane Systematic Review on PFMT for women with UI, and only those of moderate to high quality (>6 on the PEDro scale) were retained. Eighteen articles met the inclusion criteria and were scored by two independent reviewers using the CERT, TIDieR, and CONTENT instruments. The completeness of intervention reporting was evaluated using descriptive statistics. Over half of the items on each instrument were reported less than 50% of the time. Overall, completeness of exercise reporting was 31% (5.8/16 ± 2.4) on CERT, 47% (5.6/12 ± 1.5) on TIDieR, and 46% (4.1/9 ± 1) on CONTENT. The least frequently reported items were the provider of the intervention, the equipment used, the tailoring of exercises, the rationale behind the intervention, and adherence to the intervention. PFMT parameters are not adequately reported in the primary RCTs that currently guide clinical practice.


Synthesis of hybrid biosorbent based on 1,2-cyclohexylenedinitrilotetraacetic acid modified crosslinked chitosan and organo-functionalized calcium alginate for adsorptive removal of Cu(II).
The present study is based on the synthesis of a novel hybrid biosorbent using 1,2-cyclohexylenedinitrilotetraacetic acid modified crosslinked chitosan and amino-thiocarbamate moiety functionalized sodium alginate (CDTA-CS/TSC-CA). The fabricated sorbent was employed to investigate the efficient recovery of Cu(II) from aqueous media. CDTA-CS/TSC-CA was characterized using Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). Analysis confirmed the successful modification of both biopolymers and subsequent loading of Cu(II) ions. CDTA-CS/TSC-CA was casted in the form of hydrogel beads having different CDTA-CS to TSC-CA mass ratios i.e., 10.0-40.0% by mass. The hydrogel beads 4CDTA-CS/TSC-CA with CDTA-CS/TSC-CA mass ratio of 40.0% was found most effective for copper sorption. Equilibrium sorption results showed that initial concentration of copper, medium pH, contact time, sorbent dosage and temperature influenced the sorption capacity (qe). Rate of sorption data was interpreted using different kinetic models and found best fitted with pseudo second order rate expression (R2 ≈ 0.99), illustrating that the rate determining step includes the electron density transfer from sorbent coordination sites to central copper ions. Crank's RIDE equation and Elovich chemisorption model (ECM) revealed the presence of two sorption phases, initially rapid sorption followed by comparatively a slow uptake. Equilibrium sorption data was well depicted by Langmuir model and maximum monolayer adsorption capacity (qm) was computed as 276.53 mg·g-1 at 298 K. Standard Gibbs free energy change, ∆G° (-19.99, -20.18 and -20.36 kJ/ mol), standard enthalpy change, ∆H° (-8.95 kJmol) and standard entropy change, ∆S° (0.04 kJ/mol K-1) values suggested that the adsorption process is spontaneous and exothermic. Hence, 4CDTA-CS/TSC-CA was found efficient biosorbent for copper removal from its dilute effluents.


Retracted: Research on Injury Causes and Prevention Effect of College Rowing Athletes Based on Multiple Regression and Residual Algorithm.
[This retracts the article DOI: 10.1155/2022/4896336.].


Magnetic resonance imaging in lissencephaly.
In a patient with clinical manifestations suggestive of brain malformation, computer-assisted tomography (CT) showed lissencephaly: agyria, pachygyria, absent opercularization, and colpocephaly. The patient did not have seizures or a typical EEG of hypsarrhythmia. By magnetic resonance imaging (MRI), using a long inversion-recovery sequence, it was possible to verify the CT-findings and to demonstrate heterotopic grey matter and missing claustrum. By MRI it was much easier to estimate the altered ratio of grey and white matter. High grey-white matter contrast of inversion-recovery scans and the possibility of imaging the brain in sagittal, coronal and transverse planes make MRI the method of choice for the evaluation of lissencephaly and other brain malformations. In this case it helped to verify lissencephaly as one aspect of an unknown clinical entity of type-I-lissencephaly, defective structure of lymphatic nodes, a polyarthritis-like clinical picture, hypodontia, and flaring of the ribs.


Mutagenicity and cytotoxicity of congeners of two classes of nitroso compounds in Chinese hamster ovary cells.
The induction of mutation by certain nitrosamidines and nitrosamides has been quantitated utilizing the hypoxanthine--guanine phosphoribosyl transferase (HGPRT) locus in Chinese hamster ovary cells. Dose--response relationships for cytotoxicity and mutagenicity are presented for N-methyl-N-nitrosourea (MNU), N-ethyl-N-nitrosourea (ENU), N-butyl-N-nitrosourea (BNU), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). Based on the concentration of each agent required to kill 90% of the cells, the following order of cytotoxicity was observed: MNNG greater than ENNG greater than MNU greater than ENU greater than BNU. This is the same order of potency as observed for mutation induction per unit concentration of mutagen.


Does symptom severity predict response to low-dose onabotulinumtoxinA for the treatment of urgency urinary incontinence?
Intradetrusor onabotulinumtoxinA is a third-line treatment for urgency urinary incontinence (UUI) which is customarily reserved for severe disease. We sought to determine if symptom severity predicts the proportional response to onabotulinumtoxinA and whether low-dose injection may be an appropriate treatment for mild-moderate symptoms. This prospective cohort study compared patients with urgency urinary incontinence who were recruited from the Urogynecology Clinic with mild-moderate (2-9 episodes/3-day diary) and severe UUI (>9 episodes/3-day diary) symptoms. Twenty-eight subjects were treated (11 mild-moderate, 17 severe) with 50 units of intradetrusor onabotulinumtoxinA. Voiding diaries and validated questionnaires (UDI-6 and IIQ-7) were collected at baseline and one, six, and twelve months post-treatment. The primary outcome was the difference in percent reduction in UUI episodes per 3-day diary at one month. Secondary outcomes included differences in absolute reduction of UUI events, treatment success rate (defined as greater than 50% reduction in UUI episodes), changes in UDI-6 and IIQ-7 questionnaire scores, and rates of urinary retention, self-catheterization, and urinary tract infection. Normally distributed data are presented as means with standard deviations (SD) and groups were compared using the two sample t-test. Data that were not normally distributed are presented as medians with the interquartile range (IQR) and were compared using the Wilcoxon rank sum test. The mild-moderate group showed median improvement; 100% (IQR: 100%, 100%) and severe group; 81% (IQR: 35%, 100%), p < 0.019. Both had significant improvement in UUI episodes; the mild-moderate group decreased by four and the severe group by 15. No differences were noted in percent reduction between groups. There was no association between baseline severity and percent reduction in UUI episodes (rs = 0.127, p = 0.544); however, absolute reduction was highly correlated (rs = -0.821, p < 0.001). Treatment success was 90% in mild-moderate and 73% in the severe group (p = 0.615). Complications included urinary tract infections (25%) and intermittent catheterization (3.6%). Patients with both mild-moderate and severe symptoms showed a statistically significant improvement in UUI events from baseline to one month, but no difference between the groups in proportional improvement or treatment success.


The healing of colonic anastomoses after early intraperitoneal chemotherapy: an experimental study in rats.
Early postoperative intraperitoneal administration of 5-fluorouracil (5-Fu) is a logical adjuvant treatment of patients with resectable colonic cancers. It is easier and less invasive than the intraportal administration of the drug. However, before applying the procedure to humans it must be demonstrated than it does not disturb the healing of recent colonic anastomoses. Colonic sutures were performed in 78 male Wistar rats. The animals then either served as controls or received intraperitoneal 5-Fu during 5 days starting on the first, third, or seventh postoperative day. No statistical difference was observed between treated and control groups when observing the incidence of anastomotic spontaneous disruptures, anastomotic healing strength, or the weight of the animals. It is concluded that early intraperitoneal 5-Fu administration does not impair the healing of recent colonic anastomoses in rats.


A multicenter study on PIVKA reference interval of healthy population and establishment of PIVKA cutoff value for hepatocellular carcinoma diagnosis in China.
The aim of this study was to investigate the reference interval of protein-induced vitamin K absence or antagonist-II (PIVKA-II) in China population and to evaluate its medical decision level for hepatocellular carcinoma (HCC) diagnosis. To determine the reference range for Chinese individuals, a total of 855 healthy subjects in five typical regions of China were enrolled in this study to obtain a 95% reference interval. In a case-control study which recruited the subjects diagnosed with HCC, metastatic liver cancer, bile duct cancer, hepatitis, cirrhosis, other benign liver diseases and the subjects administrated anticoagulant, receiver operating characteristic analysis was used to determine PIVKA-II cutoff value for a medical decision. The concentration of PIVKA-II had no relationship with age or gender and that region was a significant factor associated with the level of PIVKA-II. The 95% reference interval determined in this study for PIVKA-II in Chinese healthy individuals was 28 mAU/mL, and the cutoff value which to distinguish patients with HCC from disease control groups is 36.5 mAU/mL. In clinical applications, it is recommended that each laboratory chooses their own reference interval based on the regional population study or cutoff value for disease diagnosis.


Down-regulated ECRG4 expression in breast cancer and its correlation with tumor progression and poor prognosis--A short Report.
Recently, we identified the esophageal carcinoma related gene 4 (ECRG4) as a novel candidate tumor suppressor gene and a promising therapeutic target in nasopharyngeal carcinoma (NPC). In addition, we found that reduced ECRG4 expression in NPC was associated with promoter hypermethylation. The aim of the current study was to assess the expression status of the ECRG4 protein in breast cancer and to clarify its clinicopathological significance and potential prognostic implications. Western blotting was used to examine ECRG4 protein levels in 20 paired breast cancer tissues and adjacent noncancerous tissues. In addition, we performed ECRG4 immunohistochemistry on 113 clinicopathologically well-characterized breast cancer samples and assessed putative associations between its expression and overall patient survival rates. We found that ECRG4 protein expression was significantly reduced in the breast cancer tissues compared to the noncancerous tissues. Clinicopathological analyses revealed that loss of ECRG4 protein expression, observed in 41.6 % (47/113) of the primary breast cancer tissues tested, was significantly correlated with lymph node metastasis (P = 0.026), advanced tumor stage (P = 0.042) and unfavorable overall survival (P = 0.004). Additional multivariate analyses revealed that ECRG4 protein expression may serve as an independent prognostic factor for the prediction of patient survival (P = 0.033). Our data suggest that loss of ECRG4 protein expression may be involved in tumor progression and may serve as a prognostic biomarker for breast cancer.


Toxicokinetics of 14C-endosulfan in male Sprague-Dawley rats following oral administration of single or repeated doses.
Endosulfan (ES), an organochlorine (OC) insecticide that belongs to the cyclodiene group, is one of the most commonly used pesticides to control pests in vegetables, cotton, and fruits. The toxicokinetics of 14C-endosulfan following oral administration of a single dose of 5 mg/kg body weight was investigated in male Sprague-Dawley rats. Three rats were sacrificed 30 min, 1 h, 2 h, 4 h, and 8 h after dosing. 14C-endosulfan radioactivity was detected in all tissues at each time point. In a separate experiment urine and feces were collected for 96 h. The total radioactivity recovered in the excreta for 4 days was 106.8% +/- 26.2%, with fecal elimination the major route of elimination route (94.4% +/- 21.4%). The cumulative excretion in the urine for 4 days was 12.4% +/- 4.8%. Radioactivity 8 h after administration was highest in gastrointestinal (GI) tract tissue (20.28 +/- 16.35 mg ES eq./L) and lowest in muscle (0.18 +/- 0.06 mg ES eq./L). The toxicokinetic parameters obtained from 14C-endosulfan-derived radioactivity in blood were distribution half-life (T1/2 x) = 31 min and terminal elimination half-life (T1/2 y) = 193 h. Blood concentration reached its maximum (Cmax) of 0.36 +/- 0.08 mg ES eq./L 2 h after the oral dose. Endosulfan was rapidly absorbed into the GI tract in rats, with an absorption rate constant (ka) of 3.07 h(-1).


Body composition in patients with Fontan physiology: a systematic review.
Fontan circulation is a highly abnormal circulatory state that may affect various organ systems. The effect on body composition is an important factor to assess the condition of the patient. This systematic review assesses body composition and possibly related adverse outcomes in patients with a Fontan circulation, to provide an overview of current insights. Studies evaluating body composition by compartment (either fat mass or lean/muscle mass) in Fontan patients published up to April 2023 were included in this systematic review. Of 1392 potential studies, 18 studies met the inclusion criteria. In total, body composition measurements of 774 Fontan patients were included. Body composition was measured using dual-energy X-ray absorptiometry (DXA) (n = 12), bioelectrical impedance analysis (BIA) (n = 5), computer tomography (CT) (n = 1), or magnetic resonance imaging (MRI) (n = 1). All studies reported a normal body mass index (BMI) in Fontan patients, compared to controls. Five out of nine studies reported significantly higher body fat values, and twelve out of fifteen studies reported significantly lower muscle or lean mass values in the Fontan population compared to the healthy population. Unfavorable body composition in Fontan patients was associated with decreased exercise capacity, worse cardiac function, and adverse outcomes including hospital admissions and death. Conclusions: Despite having a normal BMI, Fontan patients have an increased fat mass and decreased muscle mass or lean mass compared to the healthy population. This unfavorable body composition was associated with various adverse outcomes, including a decreased exercise capacity and worse cardiac function. What is Known: • Patients with a Fontan circulation have a decreased exercise capacity compared to healthy peers, an unfavorable body composition might be a contributor to their impaired exercise capacity. What is New: • Fontan patients are predisposed to an unfavorable body composition, characterized by increased fat mass and decreased muscle mass accompanied by a normal BMI compared to the healthy population. • Among others, unfavorable body composition was associated with decreased exercise capacity, cardiac function, and increased morbidity in patients with a Fontan circulation.


Diagnostic findings and follow-up outcomes in relatives to young non-autopsied sudden death victims.
Guidelines recommend clinical assessment of relatives to young sudden cardiac death (SCD) victims in case the SCD was due to an inherited cardiac disorder. Work-up of relatives is guided by findings in the SCD victim. If post-mortem examinations have not been performed the work-up of relatives is challenged. In this retrospective study we included families referred to our tertiary referral centre between 2005 and 2018 due to a possible SCD (pSCD) in the family. Autopsy had not been performed in any of the pSCD victims. The relatives underwent cardiac work-up focusing on putative presence of inherited cardiac disorders and genetic analysis in selected cases. A family diagnosis was only established if≥1 relative was diagnosed. The families were categorised as: 1) definite inherited cardiac diagnosis, 2) borderline diagnosis, or 3) undiagnosed. We assessed 149 relatives (43 ± 16 years, 48% men) from 84 pSCD non-autopsied cases (44 ± 11 years, 79% men). In 11 (13%) families a definite inherited cardiac diagnosis was established, a borderline diagnosis in 8 (10%) families, and 65 (77%) families remained undiagnosed. One third of the diagnosed relatives were offered pharmaco- or device-based therapy. During follow-up for 4.7 ± 3.6 years no relatives from the families with definite diagnoses died. No events were seen in the groups with borderline or no diagnoses. The diagnostic yield and need for treatment in diagnosed relatives warrant work-up, also of families with non-autopsied pSCD victims. No or reduced follow-up of relatives without signs or symptoms of heart diseases may be safe.


The Use of Structural Distal Femoral Allograft for Acetabular Reconstruction of Paprosky Type IIIA Defects at a Mean 21 Years of Follow-Up.
Revision total hip arthroplasty in patients with a nonsupportive superior acetabulum often requires secondary augmentation beyond a hemispherical cup to achieve reliable fixation. Treatment options include using a higher hip center, jumbo cup, custom triflange implant, cages, or filling the superior defect with a bilobed implant, structural allograft, or metal augments. We previously reported a cohort of 31 patients treated with porous-coated hemispherical cups and distal femoral allograft for Paprosky type IIIA acetabular defects. The original cohort of 31 hips was retrospectively reviewed. Fourteen patients died with <15 years of follow-up, and 2 were lost to follow-up. This left 15 patients for evaluation including 5 males and 10 females, with an average age of 61 years (range: 37-74 years) at the time of surgery. Acetabular revision was performed with the use of a porous-coated hemispherical cup along with structural distal femoral allograft, cut to resemble the number 7, and secured with 6.5-mm cancellous screws with washers. Overall, 7 hips failed, resulting in a Kaplan-Meier survivorship of 72% at 25 years of follow-up. In surviving patients, radiographs demonstrated components to be well fixed, and average Merle d'Aubigné score increased from 5 to 10 points. There were a subset of patients that failed early (median: 6.2 years), but the remaining patients demonstrated excellent clinical and radiographic results. The use of distal femoral allograft can be considered in young patients with type IIIA acetabular defects that could benefit from restoration of bone stock.


Experimental evidence for the adaptive value of sexual reproduction.
It is generally believed that recombination by sexual reproduction is unfavourable in constant environments but is of adaptive value under changing environmental conditions. To test this theory, experimental populations of yeast (Saccharomyces cerevisiae) were set up and maintained at different levels of environmental heterogeneity. Recombination was estimated by determining sporulation rates. Sporulation rates first increased in populations living in highly variable environments, but after some time began to decrease. The decrease started last and was slowest in populations which were maintained under the same conditions for a sufficiently long time, to allow some adaptation of the gene pool to the respective environment. Patterns of genotypic variability could not be interpreted in such simple terms, but there was a statistically significant correlation between sporulation rate and genotypic variability. This correlation is to be expected because recombination generates genotypic variability. Summing up, recombination by sexual reproduction is advantageous in changing environments if the population can track the changes in the environment by changing its genotypic structure.


Extrapontine myelinolysis manifested selectively by acute severe parkinsonian syndrome. Case Report.
Osmotic demyelination syndrome (ODMS) is a rare and serious neurologic disorder with acute myelin disintegration, usually in the pontine area (central pontine myelinolysis) and to a lesser extent, even in other areas of the central nervous system (extrapontine myelinolysis). The main underlying mechanism is the change of serum osmolality with quick correction of low mineral levels, mainly hyponatraemia. Clinical manifestation is various and depends on the localization. We describe an acute isolated extrapontine myelinolysis causing acute onset of parkinsonism in a 61-year-old man who developed quickly progressing parkinsonian syndrome after the rapid correction of hyponatraemia. Brain MRI revealed lesions only in the striatum, sparing the globus pallidus. Substitution therapy with high doses of levodopa significantly improved his clinical condition. Extrapontine myelinolysis with isolated affection of basal ganglia is extremely rare. In such case, clinical manifestation of acute severe parkinsonism could be successfully treated by high dose of levodopa.


The R620W C/T polymorphism of the gene PTPN22 is associated with SLE independently of the association of PDCD1.
The gene PTPN22 is located on chromosome 1p13 and encodes a protein tyrosine phosphatase called the lymphoid-specific phosphatase (Lyp). Lyp is expressed in lymphocytes, where it physically associates through its proline-rich motif (called P1) with the SH3 domain of the protein tyrosine kinase Csk, an important suppressor of the Src family of kinases Lck and Fyn, which mediate TCR signaling. Therefore, it is said that interaction between Lyp and Csk enables these effectors to inhibit T-cell activation synergistically. It was reported that a missense single nucleotide polymorphism , R620W (rs2476601), 1858C->T encodes an amino-acid change in the P1 proline-rich motif of the gene PTPN22 and is associated with SLE in North American white individuals. PTPN22 gene polymorphisms were genotyped in 571 Swedish SLE patients and 1042 healthy controls using TaqMan SNP Genotyping Assay. Differences were observed between cases and control subjects at both the allele (chi(2)=11.2895;P=0.0007,1df) and genotype (chi(2)=10.2243;P=0.0013, 1df) levels. We also found evidence of a genetic association between PTPN22 and renal disorder (chi(2)=9.5660;P=0.0019). We then analyzed if in patients with renal disorder associations with PDCD1 and PTPN22 were independent. Our data suggest that this appears to be the case although we observed some degree of interaction.


Insulin-mediated modulation of cytochrome P450 gene induction profiles in primary rat hepatocyte cultures.
In this investigation, we examined the effects of insulin on gene induction responsiveness in primary rat hepatocytes. Cells were cultured for 72 hours either in the absence or presence of 1 microM insulin and then exposed to increasing concentrations of phenobarbital (PB; 0.01-3.5 mM). Culturing in the absence of insulin produced 1.5-2-fold increases in the induction magnitude of CYP2B1 and CYP2B2 mRNA expression resulting from PB exposures, without altering the bell-shaped dose-response curve characteristic of this agent. However, for the CYP3A1 gene, insulin removal led to a pronounced shift in both the PB-induction magnitude and dose-response relationships of the induction response, with higher levels of CYP3A1 expression resulting from exposures to lower concentrations of inducer. Insulin removal also reduced the time required to attain maximal induction of CYP2B1/2 and CYP3A1 gene expression. The insulin effects were not specific for PB induction, as insulin deprivation similarly enhanced both dexamethasone- and beta-naphthoflavone-inducible CYP3A1 and CYP1A1 expression profiles, respectively. In contrast, the level of albumin mRNA expression was reduced considerably in cells deprived of insulin. We conclude that insulin is an important regulator of inducible and liver-specific gene expression in primary rat hepatocytes.


Cysteine proteinase activity in the development of arthritis in an adjuvant model of the rat.
Cathepsin B and L activity was studied histochemically in arthritic rat ankle joints using specific synthetic substrates in a post coupling method on unfixed and undecalcified cryostat sections of rat ankle joints. Activity was strongly increased in chondrocytes and cells of the inflamed synovium with the development of arthritis induced by the synthetic adjuvant CP20961. Activity reached a maximum 20 days after induction of arthritis and decreased as the rats entered natural remission. Cathepsin B and L were at their highest level when macrophages were present in the joint space, as shown by using monoclonal antibody markers for rat macrophages (ED1 and ED2) in a biotin-avidin immunoperoxidase assay. This suggests that the macrophage infiltrate may have stimulated proteinase production in chondrocytes through cytokine release. The profile of appearance of cysteine proteinases suggests their involvement in the breakdown of cartilage and bone in the arthritic joint.


Upregulation of long noncoding RNA FERRE promoted growth and invasion of breast cancer through modulating miR-19a-5p/EZH2 axis.
It has been demonstrated that long non-coding RNA (LncRNA) plays an important regulatory role in a series of diseases. The purpose of this study is to investigate the expression of long non-coding RNA (LncRNA) FERRE and its facilitating effects on proliferation and invasion of breast cancer by regulating oncogene EZH2 through sponging with miR-19a-5p. qRT-PCR was performed to detect the expressions of FERRE and EZH2 in human breast cancer tissues and cells. CCK-8 assay was performed to evaluate the MCF-7 cells proliferation and transwell assay was performed to evaluate the MCF-7 cells migration. Correlation analysis between FERRE and miR-19a-5p was detected by statistical analysis. Bioinformatics prediction was made to detect the binding site of FERRE and miR-19a-5p and Luciferase activity was conducted to investigate the interaction between EZH2 and miR-19a-5p. Furthermore, we cloned the mice EZH2 3'-UTR into the Luciferase reporter vector and constructed miR-19a-5p binding mutants to validate the inhibited modulation of miR-19a-5p to the EZH2 expression. Results showed that expression of FERRE and EZH2 were upregulated in human breast cancer tissues and cells. qRT-PCR and CCK-8 assay showed that FERRE expression is associated with the proliferation of breast cancer cells, upregulated FERRE contributed to cell proliferation of MCF-7. Transwell assay showed that FERRE was associated with the migration ability of tumor cells, increased expression of FERRE promoted the migration and invasion of breast cancer cells. The bioinformatics prediction and Luciferase assay demonstrated that by sponging with miR-19a-5p, FERRE can serve as a molecular sponge to further regulate the expression of EZH2. We found that lncRNA-FERRE was upregulated in human breast cancer patients, which could accelerate tumor proliferation, migration and invasion as a molecular sponge by modulating the inhibitory effect of miR-19a-5p on oncogene EZH2.


Cloning and expression of the Zymomonas mobilis "production of ethanol" genes in Lactobacillus casei.
This study describes the expression of the Zymomonas mobilis genes coding for pyruvate decarboxylase (pdc) and alcohol dehydrogenase (adh) in Lactobacillus casei 686. To promote transcription, the promoter and ribosome binding site (RBS) from the Lactococcus lactis subsp. lactis-derived vector, pMGE36e, were inserted upstream of the pdc gene. The former sequences were positioned such that translation of pdc was coupled to translation of an 81-base pair open reading frame terminating within the pdc initiation site. The recombinant plasmid (pRSG02) was electroporated into L. casei, and transformants were obtained. Northern analysis confirmed the production of a 3. 1-kb transcript corresponding to the predicted size of the PET operon. Western blot analyses revealed that the recombinant strain expressed both enzymes. The recombinant produced more than twice the ethanol produced by the parental L. casei strain.


Histochemical development of myofibres in neonatal piglets.
The periodic acid-Schiff (PAS) reaction and tests for glycogen phosphorylase, oxidative enzymes and acid-stable and alkali-stable adenosine triphophatase (ATPase) were used to determine the degree of histochemical differentiation between myofibres of sartorius muscles from neonatal piglets. Within 24 h of birth, the ratio of myofibres with acid-stable ATPase to those with acid-labile ATPase was 1:21-0. By 10 days the ratio had changed to 1:5-2. Mean minimum myofibre diameters (all histochemical types combined) increased steadily after birth although diameters of myofibres with acid-stable ATPase showed no increase until 6 days. By 10 days, consistent differentiation was observed with the alkali-stable ATPase and glycogen phosphorylase reactions but not with the PAS reaction. During the 10 day neonatal period, all types of myofibres contained large or moderate numbers of mitochondria.


Fufang Zhenzhu Tiaozhi (FTZ) capsule ameliorates diabetes-accelerated atherosclerosis via suppressing YTHDF2-mediated m6A modification of SIRT3 mRNA.
Fufang Zhenzhu TiaoZhi (FTZ), a Chinese medicinal decoction, has continuously been used to treat metabolic syndrome. Atherosclerosis is the main pathological basis of cardiovascular disease. The N6 methyladenosine (m6A) modification is a highly dynamic and reversible process involving a variety of important biological processes. Here, we investigated the therapeutic effects and mechanism of FTZ in diabetes-accelerated atherosclerosis. Doppler ultrasonography was used to examine the carotid intima-media thickness and plaque area in diabetic atherosclerosis patients. HFD mice were injected with streptozotocin to induce diabetes. HE and Oil red O staining were used to assess the effect of FTZ on lipid deposition. HUVECs were induced with HG/ox-LDL as a model of diabetic atherosclerosis. Furthermore, application of m6A methylation level kit, qRT-PCR, Western blot, tunel staining, reactive oxygen species staining and mPTP staining were performed to analyze the detailed mechanism. Clinical trials of FTZ have shown obvious effect of lowering blood glucose and blood lipids. These effects were reversed after FTZ intervention. Compared with the control, lipid deposition decreased significantly after FTZ administration. FTZ reduced endothelial cell apoptosis. At the same time, we found that FTZ reversed the increase of methylation reader YTHDF2 caused by ox-LDL treatment. Subsequently, we discovered that YTHDF2 degraded SIRT3 mRNA, leading to endothelial cell apoptosis and oxidative stress. FTZ attenuated diabetes-accelerated atherosclerosis by decreasing blood glucose and serum lipids levels, and increased endothelial cell antioxidant capacity, inhibited endothelial cell apoptosis via inhibiting YTHDF2-mediated m6A modification of SIRT3 mRNA, which reduced mRNA degradation.


Repair of Unstable Posterior Sternoclavicular Dislocation Using Nonabsorbable Tape Suture and Tension Band Technique: A Case Report with Good Results.
Posterior sternoclavicular joint dislocation (PSCJD) is quite a rare condition. Nearly half of the closed reduction attempts fail due to various reasons. In this paper, we present a 25-year-old male patient who was admitted to the emergency department in our hospital after having a motor-vehicle accident. It was decided to do PSCJD after physical and imaging studies. Following necessary preparations, closed reduction was attempted with abduction-traction maneuver under general anesthesia; however, adequate stabilization could not be achieved and redislocation was detected during control. Therefore, joint was stabilized with tension band technique using 6 mm polyamide nonabsorbable type suture during open reduction. Painless and complete range of motion in shoulder was achieved at the postoperative 10th week.


Simulation of cortical cholinergic deficits--a novel experimental approach to study pathogenetic aspects of Alzheimer's disease.
Cholinergic lesion paradigms have been used to study the role of the cholinergic system in cognitive function, and its implication in cognitive deficits that occur in Alzheimer's disease. In the last few years an increasing number of studies have applied neurotoxins including excitotoxins or cholinotoxins to produce reductions in cortical cholinergic activity. One of the most serious limitations of these lesion paradigms is the fact that the cytotoxins used are far from being selective to cholinergic cells. Recently, a monoclonal antibody to the low-affinity nerve growth factor (NGF) receptor, 192IgG, coupled to a cytotoxin, saporin, has been described as an efficient and selective immunotoxin for the NGF-receptor bearing cholinergic neurons in rat basal forebrain. Here we demonstrate the usefulness of 192IgG-saporin as a powerful tool for producing an animal model with selective and specific basal forebrain cholinergic lesions in rats which can be applied to simulate some neurochemical sequelae of Alzheimer's disease including cholinergic mechanisms in processing of the amyloid precursor protein, and could be of particular value to elaborate and to test therapeutical strategies compensating for the reduced cortical cholinergic input.


The efficacy of extracorporeal magnetic stimulation for treatment of chronic prostatitis/chronic pelvic pain syndrome patients who do not respond to pharmacotherapy.
To investigate the effect of extracorporeal magnetic stimulation (EMS) on symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men who did not respond to pharmacotherapy. Patients with chronic pelvic pain and/or voiding symptoms in the absence of urinary tract infection for at least 3 months in spite of medication were included in this study. All patients underwent EMS for 6 weeks for a total of 12 sessions. The primary endpoint was the changes in total and pain scores of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) at 24 weeks after treatment. Patients were also evaluated by International Prostate Symptom Score (IPSS), voiding diary, Benefit Satisfaction and Willingness (BSW) questionnaire, and patient perception of symptom improvement (PPSI). A total of 46 men were included, and data from 37 patients who completed this study were analyzed. The baseline vs 24 weeks mean NIH-CPSI score was total score 25.0 ± 6.9 vs 15.6 ± 7.7, pain score 11.8 ± 3.7 vs 6.9 ± 4.7 (all P <.05). Total and subdomain sums of IPSS improved significantly after treatment, and the improvements were maintained until 24 weeks. Patient voiding diaries demonstrated a tendency toward a decrease in all subdomains after treatment. In BSW, >70% of patients reported positive answers to each domain at 24 weeks after treatment. PPSI measured by the visual analog scale was maintained from immediately after treatment until 24 weeks. EMS offers a new treatment option for patients with CP/CPPS who do not respond to pharmacotherapy.


Synthesis, spectral characterization and crystal structure of N-2-hydroxy-4-methoxybenzaldehyde-N'-4-nitrobenzoyl hydrazone and its square planar Cu(II) complex.
A new aroyl hydrazone, N-2-hydroxy-4-methoxybenzaldehyde-N'-4-nitrobenzoyl hydrazone (H2L) and its mixed ligand Cu(II) complex [CuLpy] [py, pyridine] have been prepared. The ligand is characterized by elemental analysis, electronic, infrared and NMR spectral studies and the complex by electronic, infrared, EPR spectral studies and the magnetic susceptibility data. The structures of the compounds were determined by single crystal X-ray diffraction studies. Both the ligand and the Cu complex crystallize into a triclinic lattice with a space group of PI. From the crystal studies, it is concluded that the ligand molecule exits in the keto form in the solid state, while at the time of complexation, it tautomerises into the enol form. The complex is formed by the double deprotonation of the ligand molecule--both the phenolic and the enolic protons.


A novel combination of enzymatic hydrolysis and microbial fuel cell for electricity production from bakery waste.
This work developed a novel two-stage bioprocess for electricity generation from bakery waste (BW). In the first stage, commercial glucoamylase was utilized to hydrolyze the BW to produce soluble BW hydrolysate. It was found that 100 g BW could be converted to 32 g hydrolysis solid and 760 mL BW hydrolysate. The highest glucose production of 21.9 g/L could be achieved within 5 h. In the second stage, the soluble BW hydrolysate was utilized as feedstock for electricity generation in microbial fuel cell (MFC). The maximum voltage of 0.386 V was obtained. The power density reached a peak value of 29.96 mW/m2 when the external resistance was 1090 Ω. It could be potentially utilized to transform high-starch containing raw materials into biofuels production which could reduce the cost of biofuels production effectively for industrial application.


Selecting patients for gastrectomy in metastatic esophago-gastric cancer: clinics and pathology are not enough.
To evaluate the impact on overall survival (OS) of gastrectomy in asymptomatic metastatic esophago-gastric cancer. Five hundred and thirteen patients were included. The role of surgery and other clinico-pathological factors was evaluated by univariate and Cox regression analyses. OS was the primary end point. Multivariate analysis confirmed that gastrectomy was a predictor of longer OS (p < 0.001), as well as preserved performance status and benefit from first-line chemotherapy. None of the investigated clinico-pathological variables identified preferable candidates for surgery (all p > 0.05). Palliative gastrectomy might play a role in asymptomatic metastatic esophago-gastric cancer patients with good performance status who received benefit from first-line chemotherapy. Future prospective trials integrating tumor biology among inclusion criteria may help defining the optimal candidates.


Action of carbon tetrachloride in the reconstituted monooxygenase system using partially purified cytochrome P-450 and P-448.
In the cytochrome P-450-reconstituted system, CCl4 stimulated NADPH-dependent lipid peroxidation of the system containing the P-450 form to a much greater extent than that of the system containing the P-448 form. When the P-450-reconstituted system was preincubated in the presence of both NADPH and CCl4, 7-ethoxycoumarin O-deethylase, aminopyrine N-demethylase and aniline hydroxylase activities were decreased by 40-60%, whereas, with P-448 form reconstituted system, no suppression was observed in these enzyme activities or in 7-ethoxyresorufin O-deethylase activity. These observations suggest that the P-450 form, but not the P-448 form, is active in metabolizing CCl4 to a reactive species that subsequently impairs the hemoprotein.


In silico investigation on the mutational analysis of BRCA1-BARD1 RING domains and its effect on nucleosome recognition and ubiquitination.
The BRCA1-BARD1 complex is a crucial tumor suppressor E3 ubiquitin ligase involved in DNA double-stranded break repair. The BRCA1-BARD1 RING domains interact with UBE2D3 through the BRCA1 interface and this complex flexibly tether to the nucleosome core particle (NCP), where BRCA1 and BARD1 interacts with histone H2A and H2B of NCP. Mutations in the BRCA1-BARD1 RING domains have been linked to familial breast and ovarian cancer. Seven mutations were analyzed to understand their effect on the binding interface of protein partners and changes in conformational dynamics. Molecular dynamics simulations revealed that mutant complexes were less conformationally flexible than the wildtype complex. Protein-protein interaction profiling showed the importance of specific molecular interactions, hotspot and hub residues, and some of these were lost in the mutant complexes. Two mutations (BRCA1L51W-K65R and BARD1C53W) hindered significant interaction between protein partners and may prevent signaling for ubiquitination of histones in NCP and other cellular targets. The structural compactness and reduced significant interaction in mutant complexes may be the possible reason of preventing ubiquitination and hinder DNA repair, resulting cancer.


[99mTc]Tc-DGA1, a Promising CCK2R-Antagonist-Based Tracer for Tumor Diagnosis with Single-Photon Emission Computed Tomography.
Radiolabeled gastrin analogues have been proposed for theranostics of cholecystokinin subtype 2 receptor (CCK2R)-positive cancer. Peptide radioligands based on other receptor antagonists have displayed superior pharmacokinetics and higher biosafety than agonists. Here, we present DGA1, a derivative of the nonpeptidic CCK2R antagonist Z-360 carrying an acyclic tetraamine, for [99mTc]Tc labeling. Preclinical comparison of [99mTc]Tc-DGA1 with [99mTc]Tc-DG2 (CCK2R-agonist reference) was conducted in HEK293-CCK2R/CCK2i4svR cells and mice models, qualifying [99mTc]Tc-DGA1 for further study in patients with CCK2R-positive tumors and single-photon emission computed tomography/CT.


Nucleotide sequence of the 5'-terminus of Newcastle disease virus and assembly of the complete genomic sequence: agreement with the "rule of six".
We have determined the sequences of the 5' ends of three strains of Newcastle disease virus, permitting the assembly of the entire genomic sequence, which amounts to 15,186 nucleotides. This length is in agreement with the rule of six, which has been shown to determine replication efficiency in similar viruses. Comparison of the extreme 5' end of the trailer sequence with that of the 3'-terminal leader sequence of the virus reveals a high degree of complementarity. Variation between the 5'-terminal sequences of the different strains reveals the presence of alternative L gene polyadenylation signals, leading to correspondingly different trailer lengths.


Antisense lncRNA FOXC2-AS1 promotes doxorubicin resistance in osteosarcoma by increasing the expression of FOXC2.
Recent efforts have revealed that numerous natural antisense lncRNAs play a crucial role in the regulation of cancer biology. Here, based on our previous study, we further identified that the lncRNA FOXC2-AS1 and its antisense transcript FOXC2 are positively up-regulated in doxorubicin-resistant osteosarcoma cell lines and tissues, correlate with poor prognosis and promote doxorubicin resistance in osteosarcoma cells in vitro and in vivo. In addition, FOXC2-AS1 and FOXC2 are mainly located in the cytoplasm and form an RNA-RNA double-stranded structure in the overlapping region, which is necessary for FOXC2-AS1 to regulate the expression of FOXC2 at both the transcription and post-transcription levels. In addition, transcription factor FOXC2 also contributes to doxorubicin resistance through inducing the expression of the classical multi-drug resistance-related ABCB1 gene similar to FOXC2-AS1. Thus, we concluded that the lncRNA FOXC2-AS1 may promote doxorubicin resistance in OS by increasing the expression of transcription factor FOXC2, further facilitating ABCB1 expression. These findings demonstrate the potential underlying mechanism of FOXC2-AS1 in the regulation of doxorubicin resistance in OS and possibly provide a novel reversing target.


Inferring correlations associated to causal interactions in brain signals using autoregressive models.
The specific connectivity of a neuronal network is reflected in the dynamics of the signals recorded on its nodes. The analysis of how the activity in one node predicts the behaviour of another gives the directionality in their relationship. However, each node is composed of many different elements which define the properties of the links. For instance, excitatory and inhibitory neuronal subtypes determine the functionality of the connection. Classic indexes such as the Granger causality (GC) quantifies these interactions, but they do not infer into the mechanism behind them. Here, we introduce an extension of the well-known GC that analyses the correlation associated to the specific influence that a transmitter node has over the receiver. This way, the G-causal link has a positive or negative effect if the predicted activity follows directly or inversely, respectively, the dynamics of the sender. The method is validated in a neuronal population model, testing the paradigm that excitatory and inhibitory neurons have a differential effect in the connectivity. Our approach correctly infers the positive or negative coupling produced by different types of neurons. Our results suggest that the proposed approach provides additional information on the characterization of G-causal connections, which is potentially relevant when it comes to understanding interactions in the brain circuits.


Omega-3 polyunsaturated fatty acids to optimize cognitive function for military mission-readiness: a systematic review and recommendations for the field.
There has been interest in identifying whether nutrients might help optimize cognitive performance, especially for the military tasked with ensuring mission-readiness. This systematic review assesses the quality of the evidence for n-3 polyunsaturated fatty acids (PUFAs) across various outcomes related to cognitive function in healthy adult populations in order to develop research recommendations concerning n-3 PUFAs for mission-readiness. PubMed, CINAHL, Embase, PsycInfo, and the Cochrane Library were searched. Peer-reviewed randomized controlled trials published in the English language were eligible. Thirteen included trials were assessed for methodological quality, and descriptive data were extracted. Of the acceptable-quality (n = 8) and high-quality (n = 1) studies, 2 produced no statistically significant results, 5 produced mixed results, and 2 did not report between-group results. Results indicate that ingestion of n-3 PUFAs does not significantly alter cognitive performance in cognitively healthy persons. Studies exposing subjects to adverse circumstances that would be most relevant for drawing conclusions specifically for the military population are lacking. Several research recommendations are offered to enhance understanding of the role of fatty acids on cognitive functioning.


[Pathological Fractures of the Humerus: Experience with 76 Cases in a Musculoskeletal Oncology Centre].
Pathological fractures can be caused by numerous local and systemic processes. The humerus is one of the commonest sites of pathological, tumour-associated fractures. In a retrospective study, 76 cases of pathological fractures of the humerus were analysed; 57 (75 %) were caused by a malignant disease, 19 fractures were associated with benign musculoskeletal disorders (25 %). The grade of the tumour, treatment strategy, intra- and postoperative complications, and survival rates in malignant tumours were documented. Two thirds of fractures were localised in the proximal third of the humerus. In 59 % of patients, malignant lesions were metastases (mainly renal cell, breast, lung and prostate cancer), followed by haemato-oncological diseases and primary sarcomas. Most benign tumours were simple bone cysts and enchondromas. A total of 70 patients were treated surgically and only 6 conservatively. Most malignant tumours were treated with compound osteosynthesis and tumour prostheses. Complications in both groups were rare. The demographic transition - with an increasing number of malignancies on the one hand and improved life expectancy under modern, adjuvant therapies on the other - will become a challenge in the treatment of pathological fractures of the humerus for a variety of disciplines.


Change of QT variability index during general anesthesia.
The QT variability index (QTVI)-a non-invasive measure of beat-to-beat QT interval (QTI) fluctuations-is related to myocardial repolarization lability. The QTVI represents the relationship between QTI and the RR interval. Elevated QTVI is associated with an increased risk of malignant ventricular arrhythmias and sudden death. We investigated the influence of general anesthesia and tourniquets on the QTVI. We studied fifty patients who received total knee replacement arthroplasty under sevoflurane anesthesia. We measured QTI, corrected QTI (QTc), T-wave peak-to-end interval (TPE), QTVI, and heart rate variability. All variables were calculated at baseline (B), 30 min after general anesthesia (A), 30 min (TQ1) and 60 min (TQ2) after tourniquet inflation, and at tourniquet deflation (TQR). Prolongation of QTI was detected at all times, and QTc was significantly prolonged TQR. TPE was unchanged during general anesthesia. The QTVI was significantly decreased and more negative during anesthesia and tourniquet inflation. After deflation of the tourniquet, the QTVI was restored to preanesthetic values. Low frequency (LF) was significantly decreased during general anesthesia, but high frequency (HF) was somewhat maintained, except at TQ2. The LF/HF ratio was significantly decreased at A and TQ2. Sevoflurane based general anesthesia induced repolarization stability and, more negativity of the QTVI, in patients undergoing total knee replacement arthroplasty.


Simultaneous determination of three iridoid glycosides of Rehmannia glutinosa in rat biological samples using a validated hydrophilic interaction-UHPLC-MS/MS method in pharmacokinetic and in vitro studies.
The purpose of this study was to develop a method for simultaneous analysis of aucubin, catalpol, and geniposide, which are representative iridoid glycoside constituents of Rehmannia glutinosa, in rat plasma, urine, and feces using hydrophilic interaction ultra high-performance liquid chromatography with tandem mass spectrometry. The three components were separated using 10 mmol/L aqueous ammonium formate containing 0.01% (v/v) formic acid and acetonitrile as a mobile phase by gradient elution at a flow rate of 0.2 mL/min, equipped with a Kinetex® HILIC column (50 × 2.1 mm, 2.6 μm). Quantitation of this analysis was performed on a triple quadrupole mass spectrometer employing electrospray ionization and operated in multiple reaction monitoring mode. The chromatograms showed high resolution, sensitivity, and selectivity with no interference with plasma constituents. In all three iridoid glycosides, both the intra- and interbatch precisions (coefficient of variation %) were less than 4.81%. The accuracy was 96.56-103.55% for aucubin, 95.23-106.21% for catalpol, and 94.50-104.16% for geniposide. The developed analytical method satisfied the criteria of international guidance and was successfully applied to pharmacokinetic studies including oral bioavailability of aucubin, catalpol, and geniposide, and their urinary and fecal excretion ratios after oral or intravenous administration to rats. The new method was also applied to measure plasma protein binding ratios in vitro.


A case of Sweet syndrome associated with human granulocytic anaplasmosis.
Acute febrile neutrophilic dermatosis, or Sweet syndrome (SS), is a condition that is presumed to be triggered by infectious disease agents. We report a case of SS associated with human granulocytic anaplasmosis (HGA), which is of interest because Anaplasma phagocytophilum infects, multiplies in, and disrupts the function of neutrophils, the key infiltrating cell in SS. A patient with initial dermatologic manifestations of SS who did not respond to standard SS treatment was suspected to have concurrent HGA with the demonstration of leukopenia, thrombocytopenia, and elevated hepatic transaminase levels. The HGA diagnosis was established when morulae in neutrophils were observed on a peripheral blood smear, a finding confirmed by both serologic examination and polymerase chain reaction on the skin biopsy specimen used to establish the SS diagnosis. The significant involvement of neutrophils with both SS and HGA warrants a broader search for additional cases that may further define whether pathogenetic linkages could exist.


Cloning and characterization of a naturally occurring soluble form of TGF-beta type I receptor.
Transforming growth factor-beta1 (TGF-beta1) has been implicated to play an important role both in the process of normal development and in the pathogenesis of a wide variety of disease processes, including those of the kidney. TGF-beta1 regulates diverse cellular functions via a heteromeric signaling complex of two transmembrane serine/threonine kinase receptors (types I and II). Several distinct type I receptors have been described and are thought to determine specificity of the TGF-beta response and confer multifunctionality. This report reveals the cloning of a novel, naturally occurring soluble form of TGF-beta type I receptor, designated sTbetaR-I, from a rat kidney cDNA library. In vivo expression of a mRNA transcript encoding the sTbetaR-I, which lacks the transmembrane and cytoplasmic domains, is confirmed by RT-PCR followed by Southern blot analysis and by RNase protection assay. The sTbetaR-I mRNA abundance is greater in the neonatal rat kidney compared with the adult rat kidney. Furthermore, sTbetaR-I is a functional protein capable of binding TGF-beta1 ligands in the presence of a TGF-beta type II receptor on the cell surface, as determined by affinity cross-linking with 125I-labeled TGF-beta1. Studies using p3TP-Lux reporter construct reveal that this novel protein may function as a potentiator of TGF-beta signaling. The discovery of a sTbetaR-I provides an additional level of complexity to the TGF-beta receptor system.


Orderly Steps in Progression of JC Virus to Virulence in the Brain.
Progressive multifocal leukoencephalopathy is a neurodegenerative disease caused by demyelination in the brain. The demyelination is due to infection of oligodendroglial cells by polyomavirus JC, a circular DNA virus. The virus resides as an archetype form in uroepithelial cells and bone marrow of more than 70% of adults, in whom it seldom causes overt symptoms. The JC viral form infecting the brain differs from the archetype. This viral form contains two deletions and a duplication in the non-coding control region that are thought to be derived from the archetype. These rearrangements are necessary for neurovirulence. This review considers how these rearrangements occur in the context of transit to the brain and adaptation to infect glial cells.


Effects of local density on fecundity and mating speed for periodical cicadas.
The relationship between local density of adult periodical cicadas (Magicicada septendecim) and fecundity was investigated at 3 sites in 1979 and 6 sites in 1980. In 1979, a sample taken 9 days after the emergence peak showed no significant differences in the number of vitellogenic follicles contained by females from the three sites. A later sample, taken 22 days after the emergence peak, revealed significant between-site differences in the number of follicles per female. Individuals from the densest site contained over 50% more follicles than females from the lowest density site. In 1980, there was again a significant between-site difference in fecundity. Females from sites of higher density contained more follicles than females from less dense sites.The rate at which females mated was independent of local adult density. At all sites, most females had successfully mated by the end of the emergence period. All females required at least 5 days and usually longer before mating and ovipositing.Earlier work demonstrated that the ratio of offspring: adults was greater at sites of higher emergence density than at low lensity sites. The pattern of inverse density-dependent fecundity, reported here, undoubtedly contributes to this effect. However, density dependent mating speed does not appear to contribute to this effect.


Effects of vegetation spatial pattern on erosion and sediment particle sorting in the loess convex hillslope.
To address the problem of serious soil erosion on the Loess Plateau, under the conditions of limited vegetation measures, the runoff erosion characteristics and erosion sediment sorting characteristics of vegetation at different positions on the upper slope of convex hillslopes are investigated, and the optimal vegetation spatial pattern is proposed according to the benefits of water storage and sediment reduction at different vegetation positions. The fluctuation degree of flow discharge per unit area of different vegetation spatial patterns is small, and the variation process of sediment discharge per unit area of each vegetation spatial pattern fluctuated sharply with the increase of runoff time. After planting vegetation on the slope, the total runoff yield and sediment yield were reduced. The runoff yield reduction benefit was 19.65% when the grass belt was 6 m away from the slope top; and the sediment yield reduction benefit was more than 70% when the grass belt was 2 m away from the slope top. Under the condition of hydraulic erosion on the slope covered with vegetation, the erosion particles are mainly fine particles, with high silt content and relatively small sand content. The farther the vegetation is arranged from the slope top, the more easily silt of size 0.002-0.05 mm is eroded. The higher effectiveness in terms of reductions of both runoff and sediment yields were obtained when the vegetation is planted in the proximity of the end of the length of the slope.


Heat-treated Saccharomyces cerevisiae for antimony speciation and antimony(III) preconcentration in water samples.
An analytical method was developed for antimony speciation and antimony(III) preconcentration in water samples. The method is based on the selective retention of Sb(III) by modified Saccharomyces cerevisiae in the presence of Sb(V). Heat, caustic and solvent pretreatments of the biomass were investigated to improve the kinetics and thermodynamics of Sb(III) uptake process at room temperature. Heating for 30 min at 80 degrees C was defined as the optimal treatment. Antimony accumulation by the cells was independent of pH (5-10) and ionic strength (0.01-0.1 mol L(-1)). 140 mg of yeast and 2h of contact were necessary to ensure quantitative sequestration of Sb(III) up to 750 microg L(-1). In these conditions, Sb(V) was not retained. Sb(V) was quantified in sorption supernatant by inductively coupled plasma mass spectrometry (ICP-MS) or inductively coupled plasma optical emission spectrometry (ICP-OES). Sb(III) was determined after elution with 40 mmol L(-1) thioglycolic acid at pH 10. A preconcentration factor close to nine was achieved for Sb(III) when 100mL of sample was processed. After preconcentration, the detection limits for Sb(III) and Sb(V) were 2 and 5 ng L(-1), respectively, using ICP-MS, 7 and 0.9 microg L(-1) using ICP-OES. The proposed method was successfully applied to the determination of Sb(III) and Sb(V) in spiked river and mineral water samples. The relative standard deviations (n=3) were in the 2-5% range at the tenth microg L(-1) level and less than 10% at the lowest Sb(III) and Sb(V) tested concentration (0.1 microg L(-1)). Corrected recoveries were in all cases close to 100%.


The contribution of common and rare genetic variants to variation in metabolic traits in 288,137 East Asians.
Metabolic traits are heritable phenotypes widely-used in assessing the risk of various diseases. We conduct a genome-wide association analysis (GWAS) of nine metabolic traits (including glycemic, lipid, liver enzyme levels) in 125,872 Korean subjects genotyped with the Korea Biobank Array. Following meta-analysis with GWAS from Biobank Japan identify 144 novel signals (MAF ≥ 1%), of which 57.0% are replicated in UK Biobank. Additionally, we discover 66 rare (MAF < 1%) variants, 94.4% of them co-incident to common loci, adding to allelic series. Although rare variants have limited contribution to overall trait variance, these lead, in carriers, substantial loss of predictive accuracy from polygenic predictions of disease risk from common variant alone. We capture groups with up to 16-fold variation in type 2 diabetes (T2D) prevalence by integration of genetic risk scores of fasting plasma glucose and T2D and the I349F rare protective variant. This study highlights the need to consider the joint contribution of both common and rare variants on inherited risk of metabolic traits and related diseases.


Serum Concentrations of Essential Trace and Toxic Elements in Healthy and Disease-Affected Dogs.
This study was designed (i) to establish reference ranges for the essential trace element and background levels of toxic element exposure in the healthy/normal dog population, and (ii) to evaluate whether trace element concentrations vary in dogs suffering from different pathologies. Blood serum samples were collected from 187 healthy and diseased dogs at the Veterinary Teaching Hospital, Faculty of Veterinary Medicine, University of Santiago de Compostela (northwest Spain). The samples were acid digested, and the concentrations of trace elements (Co, Cr, Cu, Fe, Mn, Mo, Ni, Se and Zn) and toxic elements (As, Cd, Hg and Pb) were determined by inductively coupled plasma-mass spectrometry (ICP-MS). This enabled us to establish reference ranges for the essential trace elements and the level of toxic element exposure in dogs, and to identify several clinical situations associated with variations in trace elements in serum. Relative to concentrations in healthy control dogs, statistically significant differences were observed in the concentrations of Cu (significantly higher in hepatic, inflammatory/infectious and oncological categories), Mo (significantly higher in renal category), Se (significantly lower in gastrointestinal category) and Zn (significantly lower in gastrointestinal, inflammatory/infectious and renal categories). Trace element concentrations can be a cause or consequence of disease, and the study findings indicate that trace element determination in serum provides useful information on the pathogenesis of certain diseases. Further research on the serum concentrations of trace elements, particularly in relation to other biochemical parameters and diagnostic tools, may provide valuable information for the diagnosis of diseases in dogs and the disease prognosis.


Lipid phosphate phosphatase 3 in smooth muscle cells regulates angiotensin II-induced abdominal aortic aneurysm formation.
Genetic variants that regulate lipid phosphate phosphatase 3 (LPP3) expression are risk factors for the development of atherosclerotic cardiovascular disease. LPP3 is dynamically upregulated in the context of vascular inflammation with particularly heightened expression in smooth muscle cells (SMC), however, the impact of LPP3 on vascular pathology is not fully understood. We investigated the role of LPP3 and lysophospholipid signaling in a well-defined model of pathologic aortic injury and observed Angiotensin II (Ang II) increases expression of PLPP3 in SMCs through nuclear factor kappa B (NF-κB) signaling Plpp3 global reduction (Plpp3+/-) or SMC-specific deletion (SM22-Δ) protects hyperlipidemic mice from AngII-mediated aneurysm formation. LPP3 expression regulates SMC differentiation state and lowering LPP3 levels promotes a fibroblast-like phenotype. Decreased inactivation of bioactive lysophosphatidic acid (LPA) in settings of LPP3 deficiency may underlie these phenotypes because deletion of LPA receptor 4 in mice promotes early aortic dilation and rupture in response to AngII. LPP3 expression and LPA signaling influence SMC and vessel wall responses that are important for aortic dissection and aneurysm formation. These findings could have important implications for therapeutics targeting LPA metabolism and signaling in ongoing clinical trials.


Determination of eight synthetic food colorants in drinks by high-performance ion chromatography.
Eight synthetic food colorants (Amaranth, Brilliant Blue, Indigo Carmine, New Red, Ponceau 4R, Sunset Yellow, Tartrazine, Allura Red) were determined by high-performance ion chromatography on an anion-exchange analytical column with very low hydrophobicity and visible absorbance detection. Gradient elution with hydrochloric acid-acetonitrile effected both the chromatographic separation of these colorants and the on-line clean-up of the analytical column, which was very advantageous for routine analysis. High-performance ion chromatography may be a solution to the chromatographic analysis for some water-soluble, organic analytes with strong hydrophobicity. The method has been applied to the determination of colorants in drinks and in instant drink powder. No time-consuming pretreatment, as used in conventional liquid chromatography, was needed.


Driving Automation for Older Adults with Preclinical Alzheimer's Disease.
Older adults with preclinical Alzheimer's disease (AD) show changes in on-road driving performance. The impact of preclinical AD on using automated vehicle (AV) technology is unknown. The aim was to evaluate safety and cognitive workload while operating AV technology in drivers with preclinical AD. This cross-sectional study included 40 participants: 19 older adults (age 74.16 ± 4.78; MOCA scores 26.42 ± 2.52) with preclinical AD, evidenced by elevated cortical beta-amyloid; and 21 controls (age 73.81 ± 5.62; MOCA scores 28.24 ± 1.67). All participants completed two scenarios in a driving simulator. Scenario 1 included conditional automation with an emergency event that required a manual take-over maneuver. Scenario 2 was identical but with a cognitive distractor task. Emergency response time was the main safety outcome measure. Cognitive workload was calculated using moment-to-moment changes in pupillary size and converted into an Index of Cognitive Activity (ICA). Mann-Whitney U and independent t tests were used to compare group differences. Emergency response times were similar between drivers with preclinical AD and controls in scenario 1 (20.85 s ± 1.08 vs. 20.52 s ± 3.18; p = 0.83) and scenario 2 (14.83 s ± 7.37 vs. 13.45 s ± 10.43; p = 0.92). Likewise, no differences were found in ICA between drivers with preclinical AD and controls in scenario 1 (0.34 ± 0.08 vs. 0.33 ± 0.17; p = 0.74) or scenario 2 (0.30 ± 0.07 vs. 0.29 ± 0.17; p = 0.93). Older drivers with preclinical AD may safely operate AV technology, without increased response times or cognitive workload. Future on-road studies with AV technology should confirm these preliminary results in drivers with preclinical AD.