Ellman's reagent prevents dephosphorylation of histones during isolation of mitotic chromosomes.
Histones H1 and H3 are highly phosphorylated in mitotic HeLa cells but are rapidly dephosphorylated by endogenous protein phosphatases during the isolation of metaphase chromosomes. We show that this dephosphorylation can be prevented by including the sulfhydryl reagent 5,5'-dithiobis-(2-nitrobenzoate) (Ellman's reagent, or DTNB) in the isolation buffer. The minimal amount of DTNB required is approximately stoichiometric with the number of sulfhydryl groups in the lysate. Inhibition of the protein phosphatases can subsequently be reversed by treatment with dithiothreitol or 2-mercaptoethanol. DTNB is compatible with the isolation of either metaphase chromosome clusters or individual metaphase chromosomes. It should be useful in investigations of the structure and biochemistry of chromatin and chromosomes and in the study of possible functions for mitotic histone phosphorylation.


Assessment of the ability to model proteins with leucine-rich repeats in light of the latest structural information.
The three-dimensional structures of leucine-rich repeat (LRR)-containing proteins from five different families were previously predicted based on the crystal structure of the ribonuclease inhibitor, using an approach that combined homology-based modeling, structure-based sequence alignment of LRRs, and several rational assumptions. The structural models have been produced based on very limited sequence similarity, which, in general, cannot yield trustworthy predictions. Recently, the protein structures from three of these five families have been determined. In this report we estimate the quality of the modeling approach by comparing the models with the experimentally determined structures. The comparison suggests that the general architecture, curvature, "interior/exterior" orientations of side chains, and backbone conformation of the LRR structures can be predicted correctly. On the other hand, the analysis revealed that, in some cases, it is difficult to predict correctly the twist of the overall super-helical structure. Taking into consideration the conclusions from these comparisons, we identified a new family of bacterial LRR proteins and present its structural model. The reliability of the LRR protein modeling suggests that it would be informative to apply similar modeling approaches to other classes of solenoid proteins.


Risk Preference, Health Risk Perception, and Environmental Exposure Nexus: Evidence from Rural Women as Pig Breeders, China.
Rural women are an integral part of the agricultural economy. Still, their exposure to environmental pollution, especially in the context of risk preference and health risk perception, has not gained much attention in the existing literature. So to explore this notion, a survey and experimental data of 714 rural Chinese women as pig breeders are taken, we innovatively evaluate the degree of environmental exposure from the pre-exposure, in-exposure, post-exposure intervention of women breeders, and two-stage least squares (2SLS) method is employed to address the endogeneity issue between health risk perception and environmental exposure. The results show that rural women breeders suffer from severe environmental exposure, and the degree of environmental exposure is up to 72.102(Min = 0, Max = 100). Risk preference also emerges as a crucial determinant behind their environmental exposure, but health risk perception significantly deters the degree of environmental exposure. The health risk perception can offset risk preference effects on women breeders' environmental exposure by 15.15%. Moreover, considering the heterogeneity of the breeding scale, it is found that the impact of risk preference and health risk perception on women breeders' environmental exposure is an inverted U-shaped relationship, i.e., the results are at the turning stage when the breeding scale is 31-40 heads. Based on the empirical findings, the study offers guidelines for policymakers to enhance awareness amongst women breeders regarding health and pollution and encourage them to opt for environment-friendly breeding. Moreover, this research also has substantial guiding significance for related research on environmental exposure of rural women in other developing countries.


Lanthanide complexes for second order nonlinear optics: evidence for the direct contribution of f electrons to the quadratic hyperpolarizability.
This study descibes for the first time the nonlinear optical (NLO) properties of multipolar lanthanide complexes, Na3[Ln(dipic)3]. The "metal-induced" NLO activity enhancement is confirmed as a general property of f-block elements, and the direct participation of f electrons to the hyperpolarizability beta is strongly supported by experimental data.


Safety of equine tetanus antitoxin for prophylactic use in Ethiopia: a retrospective multi-center study.
Tetanus remains a severe life-threatening infectious disease and neurological disorder in many parts of the world, where immunization programs are suboptimal. Any human injury or trauma has the possibility of getting infected with Clostridium tetani which is the sole causative bacterium of tetanus. Evidence is available that TAT may cause anaphylaxis and late serum sickness, while there has been no study conducted in Ethiopia. The Ethiopian Ministry of Health standard treatment guideline recommends tetanus prophylaxis for all tetanus-prone wounds. This study aimed to evaluate the safety of TAT administration in adults exposed to tetanus-prone wounds in Ethiopia. The target product of this study was the equine tetanus antitoxin developed and manufactured by the ViNS Bioproducts Limited, India (Code: 130202084, A.W.No: 15/AAW/PI/02.00, DT: 25.04.2016). The product is delivered with the dose of 1000/1500 IU intramuscularly or subcutaneously to individuals at risk of tetanus infection for prophylactic purposes. The study was carried out in 11 healthcare facilities in Addis Ababa, Ethiopia, that had a relatively high clients load for tetanus-prone wounds. Medical records of patients with tetanus-prone wounds who received the equine TAT were reviewed retrospectively for any adverse events following immunization according to the World Health Organization (WHO) definition for adverse events following immunization (AEFI). There were more than 20,000 patients treated for trauma in the facilities from 2015 to 2019. Upon revision of available registration books, we identified 6000 charts to be eligible for the study, of which 1213 charts that had complete and reliable data on the AEFI profile of the TAT were included in the final analysis. The median age of the study participants was 26 years (IQR = 11 years, age range: 18-91 years) and 78% (949) were male. The tetanus-prone wounds resulted mainly from stab (44%, 535) and blunt force (30%, 362), and the most common sites of wounds were hand (22%, 270) and head (21%, 253). The most and least frequently occurring types of wounds were open wounds (77%, 930) and organ system injury (0.003%, 4), respectively. The mean time of presenting at health facilities from the onset of trauma was 2.96 h. Of the total 1231 participants, one male participant who presented within 3 h after experiencing a wound on his nose at the workplace had a severe local reaction immediately after injection of the TAT. No AEFI was recorded for the other participants. The adverse event following immunization of the equine tetanus antitoxin produced by the ViNS Bioproducts Limited was very rare. A regular review of the product's safety performance and systematic collection and analysis of adverse event reports are important to ensure the safety of the product.


Lethal hepatic injury by combined treatment of radiation plus chemotherapy in rats with thioacetamide-induced liver cirrhosis.
To assess lethal hepatic injury by combined treatment of radiation (RT) plus chemotherapy in a rat model with thioacetamide (TAA)-induced liver cirrhosis. Male Wistar rats were treated with 0.3 g/L TAA in drinking water. The development of liver cirrhosis was histologically confirmed, and the degree of liver function impairment was assessed by indocyanine green retention test (ICG R15). The established cirrhotic rats were given one of the following treatments: partial liver radiotherapy (25 Gy on about one-third of the whole liver), 5-fluorouracil (5-FU) chemotherapy (50 mg/kg), and combined treatment of partial RT plus 5-FU. The treated rats were closely followed until either death or 30 weeks after the treatment, and the postmortem liver sampling was examined for lethal hepatic injury by the treatments. The rats developed overt liver cirrhosis after 30 weeks of TAA treatment. At that time, the mean ICG R15 level in the TAA-treated rats (TAA-rats) was 14.1% +/- 0.7% compared to 4.6% +/- 0.7% in the control (p < 0.05). The 30-week survival rates in the control and TAA-rats were 100% (5/5) and 75% (6/8), respectively, after partial liver RT (p = 0.72). In the 5-FU chemotherapy group, the survival in TAA-rats was only one-half of that in the controls (100% vs. 50%, p = 0.06). Poor survival in TAA-rats was shown also in the combined group of partial RT plus 5-FU (87.5% vs. 16.7%, p = 0.06). The rats that died before the last observation time showed advanced cirrhosis with areas of lobular collapse, in contrast to the moderate cirrhotic features in those that survived. In a rat cirrhosis model with mildly impaired liver function, combined treatment of partial RT plus 5-FU resulted in significantly high incidence of lethal liver injury. The results in this study show that a combined treatment of RT plus chemotherapy in cirrhotic patients should be applied with extreme caution.


Administering intraperitoneal chemotherapy using a peritoneal port.
The IP access provided by the relatively closed system using subcutaneous portals linked to the Tenckhoff catheter has revolutionized the clinical approach to intra-abdominal tumors, especially to ovarian cancer. The development of totally implanted peritoneal access ports that diminish the risk of infection and the design of treatment regimens that do not require drainage of the drugs from the peritoneal cavity after instillation have reduced the technical complexity of IP therapy. This treatment approach is safe and can be easily administered by trained oncology nurses and physicians in an outpatient setting. The success of a program for IP chemotherapy depends on a reliable and safe access to the peritoneal cavity, such as the port. Because of the port, during the past 13 years IP chemotherapy has developed into an effective treatment, especially for ovarian cancer patients with small volume disease following laparotomy. Nurses have played a major role in the development of this treatment modality. They have become quite skillful in making assessments and intervening with appropriate nursing measures to ensure that a highly specialized and complex procedure is managed safely. Further clinical nursing research will improve the administration process of IP therapy and ultimately will improve the quality of life for patients.


Health Care Workers' Knowledge and Confidence in Personal Protective Equipment During the H1N1 Pandemic in Israel.
Healthcare workers (HCW) are at increased risk of infection during pandemics. HCW personal protective equipment (PPE) use has been shown to lower infection rates among HCW and patients. However, low compliance and misuse are frequent. Since future outbreaks are unavoidable, this issue needs to be addressed. A validated questionnaire was distributed to 617 HCWs (nurses and physicians) in 21 hospitals and 40 primary care clinics in Israel at the peak of the A/H1N1 pandemic. PPE confidence was higher among HCWs with higher tested and self-perceived knowledge. Confidence was also higher among nurses compared with physicians and among employees in hospitals compared with those in primary care clinics. Experience treating A/H1N1 patients was related to higher self-perceived knowledge and PPE confidence. High levels of PPE knowledge were significantly correlated to HCWs' confidence in PPE and may help increase PPE usage and reduce absenteeism. (Diaster Med Public Health Preparedness. 2014;0:1-8).


Southern Ocean origin for the resumption of Atlantic thermohaline circulation during deglaciation.
During the two most recent deglaciations, the Southern Hemisphere warmed before Greenland. At the same time, the northern Atlantic Ocean was exposed to meltwater discharge, which is generally assumed to reduce the formation of North Atlantic Deep Water. Yet during deglaciation, the Atlantic thermohaline circulation became more vigorous, in the transition from a weak glacial to a strong interglacial mode. Here we use a three-dimensional ocean circulation model to investigate the impact of Southern Ocean warming and the associated sea-ice retreat on the Atlantic thermohaline circulation. We find that a gradual warming in the Southern Ocean during deglaciation induces an abrupt resumption of the interglacial mode of the thermohaline circulation, triggered by increased mass transport into the Atlantic Ocean via the warm (Indian Ocean) and cold (Pacific Ocean) water route. This effect prevails over the influence of meltwater discharge, which would oppose a strengthening of the thermohaline circulation. A Southern Ocean trigger for the transition into an interglacial mode of circulation provides a consistent picture of Southern and Northern hemispheric climate change at times of deglaciation, in agreement with the available proxy records.


The interactions between hypothalamic-pituitary-adrenal axis activity, testosterone, insulin-like growth factor I and abdominal obesity with metabolism and blood pressure in men.
To examine potential interactions between abdominal obesity, endocrine, metabolic and hemodynamic perturbations. A subgroup of 284 men from a population sample of 1040 at the age of 51 y. Anthropometric measurements included body mass index (BMI, kg/m2), waist/hip circumference ratio (WHR) and abdominal sagittal diameter (D). Endocrine measurements were a modified, low dose (0.5 mg) dexamethasone suppression test (Dex), testosterone (T) and insulin-like growth factor I (IGF-I). Overnight fasting values of blood glucose, serum insulin, triglycerides, total, low and high density lipoprotein cholesterol, as well as resting heart rate and blood pressure were also determined. Arbitrary subdivisions of the men were performed to obtain subgroups of low T and IGF-I values (lowest decile, borderlines < or =13.13 nmol/I and < or =128.80 microg/l, respectively) and normal or blunted Dex. Significant relationships with BMI, WHR or D, and abnormal metabolic and hemodynamic factors, usually with the exception of total and low density lipoprotein cholesterol, were then found in subgroups with different endocrine profiles. These included men with a blunted Dex test with low T or IGF-I values, as well as men with a normal Dex test and low or normal T or IGF-I values. In addition, a group with isolated low Dex suppression, as well as another group without endocrine abnormalities, showed such relationships. These findings suggest that, in men, obesity factors are associated with metabolic and hemodynamic complications with or without the presence of perturbations of hypothalamic-pituitary-adrenal axis (HPA) regulation or low T or growth hormone secretion. In order to generate hypotheses concerning the nature of the impact of the endocrine perturbations in abdominal obesity and its metabolic complications, path analyses were performed, testing different models. These models included the endocrine measurements (Dex test, T and IGF-I), the WHR and D (representing abdominal distribution of fat), BMI (representing obesity), as well as insulin and triglyceride values (representing metabolic perturbations). The results showed a satisfactory fit (goodness-of-fit index: 0.945 - 1.0) for the path diagrams: Dex --> T/IGF-I --> WHR or D --> insulin --> triglycerides with additional direct input of blunted Dex on insulin values (see Figure 1). With BMI as determinant, essentially the same results were found with the addition of a direct pathway between Dex and BMI as well as between IGF-I-T and insulin (Figure 2). There was no evidence for pathways where WHR or BMI determined endocrine variables. The results suggest that abdominal obesity with or without endocrine abnormalities exerts a major impact on abnormalities in metabolic and hemodynamic variables. Abdominal obesity seems to be dependent on endocrine abnormalities, which in turn show direct or indirect relationships to the metabolic and circulatory variables, including a direct pathway between HPA-axis perturbations and accumulation of total body fat as indicated by the BMI. It is therefore suggested that endocrine perturbations are followed by obesity and by storage of an elevated proportion of fat in visceral depots, followed by metabolic and hemodynamic abnormalities. This is statistical evidence which is supported by evidence of mechanistic links in previous studies, suggesting the possibility of causal relationships. The results also indicate subgroups of abdominal obesity and its associated metabolic and hemodynamic abnormalities, which might be due to the input of different pathogenetic factors.


Determination of biogenic amines in fresh and processed meat by suppressed ion chromatography-mass spectrometry using a cation-exchange column.
A new method for simultaneous determination of underivatized biogenic amines based on the separation by cation-exchange chromatography and suppressed conductivity coupled with mass spectrometry detection has been developed. The method has been applied to the analysis of cadaverine, putrescine, histamine, agmatine, phenethylamine and spermidine in processed meat products. The amines were extracted from muscle tissue with methanesulfonic acid without any additional derivative step or sample clean-up. Biogenic amines were separated by the IonPac CS17 column, a cation-exchange column used with gradient elution, and detection was done by suppressed conductivity and mass spectrometry. Tyramine was simultaneously analysed by using a spectrophotometer (275 nm) before the suppressed conductivity detection. Linearity of response was obtained in the range 0.25-25 microg mL(-1). The detection limits ranged from 23 microg L(-1) for putrescine to 155 microg L(-1) for spermidine (suppressed conductivity) and from 9 microg L(-1) for agmatine to 34 microg L(-1) for spermidine (MS). Average recoveries from meat samples ranged from 85 to 97% and coefficients of variation ranged from 4.5 to 9.7%. The analysis of biogenic amines in fresh and processed meats (dry-cured, cooked and fermented products) can be used as a quality marker of raw material and for studying the relationship between their changes and the fermentation process involved in dry sausage ripening.


Electrochemical dissolution of nickel-titanium endodontic files induces periodontal ligament cell death.
Fractured endodontic files present a major problem. A novel method has been proposed to retrieve fractured nickel-titanium (NiTi) endodontic files by using electrochemical dissolution. However, the effect of file dissolution on adjacent soft tissues such as the periodontal ligament (PDL) has not been investigated. The aim of this study was to determine the effects of the dissolution products on PDL fibroblasts. Endodontic files were dissolved in sodium fluoride (NaF) by passing a 50-mA current through the NiTi files while immersed in the NaF solution. NaF/NiTi solutions were diluted with minimal essential medium-α media containing 10% serum. PDL cells were treated for up to 24 hours, and cell viability was quantified by using calcein AM to label live cells and ethidium homodimer to label dead cells. This was repeated by using artificial saliva (AS) as an alternative to NaF. NaF solution reduced PDL cell survival, and the NaF/NiTi solution further reduced PDL cell survival. AS alone did not reduce cell survival, whereas AS/NiTi solution reduced PDL cell survival. Particles that resulted from the electrochemical dissolution of NiTi files were highly cytotoxic. Electrochemically dissolving NiTi files in NaF results in solutions that are cytotoxic to PDL fibroblasts. AS may be a less toxic alternative for dissolving NiTi files.


Decreased expression of HOXB9 is related to poor overall survival in patients with gastric carcinoma.
Studies have demonstrated the implication of HOXB9 in tumorigenesis, but its role in gastric carcinoma remains unknown. To investigate the expression and prognostic value of HOXB9 in patients with gastric carcinoma. The localization and expression of HOXB9 in gastric cancer cells lines were detected by immunofluorescence and western blot. The mRNA and protein expression level of HOXB9 was detected in subjects with gastric carcinoma and paired non-cancerous tissues. Correlation between HOXB9 expression and clinicopathological parameters, the association of HOXB9 expression with the patients' survival rate was also assessed. HOXB9 was predominantly localized in the cell nucleus. A significant decrease in HOXB9 intensity in poorly differentiated gastric cancer cells is evident (P<0.01). A lower mRNA and protein expression level of HOXB9 was detected in gastric carcinoma (P<0.01). Decreased expression of HOXB9, poorly differentiation status and the presence of lymph node metastasis predict shorter overall survival (P<0.05). Patients without HOXB9 expression had a lower overall survival rate (P<0.01). Multivariate Cox regression analysis showed HOXB9 was an independent prognostic factor in gastric carcinoma (P<0.01). HOXB9 is down-regulation in gastric carcinoma and may be a novel prognostic marker for poorer clinical outcome for patients with gastric carcinoma.


Protein-protein interactions between histidine kinases and response regulators of Mycobacterium tuberculosis H37Rv.
Using yeast two-hybrid assay, we investigated protein-protein interactions between all orthologous histidine kinase (HK)/response regulator (RR) pairs of M. tuberculosis H37Rv and identified potential protein-protein interactions between a noncognate HK/RR pair, DosT/NarL. The protein interaction between DosT and NarL was verified by phosphotransfer reaction from DosT to NarL. Furthermore, we found that the DosT and DosS HKs, which share considerable sequence similarities to each other and form a two-component system with the DosR RR, have different cross-interaction capabilities with NarL: DosT interacted with NarL, while DosS did not. The dimerization domains of DosT and DosS were shown to be sufficient to confer specificity for DosR, and the different cross-interaction abilities of DosS and DosT with NarL were demonstrated to be attributable to variations in the amino acid sequences of the α2-helices of their dimerization domains.


A survey of dermatophytes isolated from human patients in the United States from 1982 to 1984.
A survey of dermatophytes isolated from patients seeking medical advice was made from 1982 to 1984 in the United States. The survey included 59 locations with data from 49 cities and one state. Listing of the isolated dermatophytes and the frequency given by percentage of total follows: Trichophyton rubrum 46.8%, T. tonsurans 33.3%, T. mentagrophytes 10.1%, Microsporum canis 4.5%, Epidermophyton floccosum 3,5%, M. gypseum and T. verrucosum both 0.7%, M. audouinii and T. terrestre both 0.1%, and T. violaceum 0.06%. No isolations of M. ferrugineum or T. schoenleinii were reported. Temporal increases were observed for frequencies of T. mentagrophytes, T. tonsurans and M. canis, and decreases occurred for frequencies of E. floccosum and T. rubrum when the data from this survey were compared by the goodness of fit test to data of the 1979 to 1981 survey. The percent of dermatophyte isolations identified as T. tonsurans correlated significantly with the percentage of blacks in cities of 100,000 or more people.


Correction: Unibody Endograft Using AFX 2 for Less Invasive and Faster Endovascular Aortic Repair: Protocol for a Multicenter Nonrandomized Study.
[This corrects the article DOI: 10.2196/16959.].


Long-term clinical outcomes of aspirin-exacerbated respiratory disease: Real-world data from an adult asthma cohort.
Aspirin-exacerbated respiratory disease (AERD) is a phenotype of severe asthma, but its disease course has not been well documented compared with that of aspirin-tolerant asthma (ATA). This study aimed to investigate the long-term clinical outcomes between AERD and ATA. AERD patients were identified by the diagnostic code and positive bronchoprovocation test in a real-world database. Longitudinal changes in lung function, blood eosinophil/neutrophil counts, and annual numbers of severe asthma exacerbations (AEx) were compared between the AERD and the ATA groups. Within a year after baseline, two or more severe AEx events indicated severe AERD, whereas less than two AEx events indicated nonsevere AERD. Among asthmatics, 353 had AERD in which 166 and 187 patients had severe and nonsevere AERD, respectively, and 717 had ATA. AERD patients had significantly lower FEV1%, higher blood neutrophil counts, and higher sputum eosinophils (%) (all p < .05) as well as higher levels of urinary LTE4 and serum periostin, and lower levels of serum myeloperoxidase and surfactant protein D (all p < .01) than those with ATA. In a 10-year follow-up, the severe AERD group maintained lower FEV1% with more severe AEs than the nonsevere AERD group. We demonstrated that AERD patients presented poorer long-term clinical outcomes than ATA patients in real-world data analyses.


Results of a Phase Ib Trial of Combination Immunotherapy with a CD8+ T Cell Eliciting Vaccine and Trastuzumab in Breast Cancer Patients.
CD8+ T cell-eliciting vaccines are being investigated in breast cancer patients. Preclinical data showed that trastuzumab increases the susceptibility of tumor cells to lysis by vaccine-generated CD8+ T cells, suggesting potential benefit of a combination immunotherapy strategy. The current trial was undertaken to demonstrate the safety of this approach. This study was designed as a dose-escalation trial enrolling clinically disease-free, human leukocyte antigen A2+ or A3+ , human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. Patients received 6-monthly inoculations of GP2+ granulocyte-macrophage colony-stimulating factor (GM-CSF) administered concurrently with standard-of-care trastuzumab. Local and systemic toxicity, as well as left ventricular ejection fraction (LVEF) were monitored. Immunologic responses were assessed in vivo by measuring the local reaction and in vitro using an interferon-γ enzyme-linked immunosorbent spot (ELISPOT) assay. Seventeen disease-free breast cancer patients were vaccinated. There were no dose-limiting or grade 3-5 local or systemic toxicities, and the median LVEF was unchanged from baseline after vaccination. Mean local reaction at initial inoculation was 28 ± 10 mm, increasing to 68 ± 8 mm at the final inoculation (p < 0.01). Mean ELISPOT response to GP2 increased from 47 ± 19 at baseline to 144 ± 60 (p = 0.13) after vaccination. Based on safety and immunologic data, the appropriate dose was determined to be 1000 μg of GP2 + 250 μg of GM-CSF. The GP2 + GM-CSF vaccine is safe and stimulates an immunologic response when administered concurrently with trastuzumab. An ongoing phase II trial is evaluating the efficacy of combining a CD8 T-cell-eliciting vaccine with trastuzumab in HER2-positive breast cancer patients.


Primaquine activates Keratin 7 to treat diabetes and its complications.
The global prevalence of type 2 diabetes mellitus (T2DM) raises the rates of its complications, such as diabetic nephropathy and cardiovascular diseases. To conquer the complications, new strategies to reverse the deterioration of T2DM are urgently needed. In this project, we aimed to examine the hypoglycemic effect of primaquine and explore its specific target. In vitro T2DM insulin resistance model was built in HepG2 cells to screen the potential anti-diabetic chemicals. On the other hand, the potential protein targets were explored by molecular docking. Accordingly, we chose C57BL/6 N mice to establish T2DM model to verify the effect of the chemicals on anti-hyperglycemia and diabetic complications. By targeting the Keratin 7 (K7) to activate EGFR/Akt glucose metabolism signaling pathway, primaquine poses a potent hypoglycemic effect. The level of acetyl-CoA is enhanced markedly, supporting that primaquine upregulates the aerobic glycolysis. Moreover, primaquine ameliorates kidney function by reducing the secretion of urinary proteins and creatinine, especially for the urea nitrogen which is significantly decreased compared to no-treatment T2DM mice. Notably, primaquine restores the level of plasma low-density lipoprotein cholesterol (LDL-C) nearly to normal, minimizing the incidence of cardiovascular diseases. We find that primaquine may reverse the dysregulated metabolism to prevent diabetic complications by stimulating EGFR/Akt signaling axis, shedding new light on the therapy of T2DM. Insulin resistance is characterized by reduced p-Akt and glucose metabolism, dominated by anaerobic glycolysis. Primaquine activates the complex made of K7 and EGFR, further stimulating Akt phosphorylation. Then, p-Akt promotes the aerobic glucose metabolism and upregulates Ac-CoA to mobilize TCA cycle, improving insulin sensitivity. The online version contains supplementary material available at 10.1007/s40200-022-01135-8.


On the distribution of senile changes in the spinal cord.
Using serially sectioned spinal cords, studies were made on the number of Alzheimer's neurofibrillary tangles, and the distribution of lipofuscin in five cases of clinically and histopathologically confirmed Alzheimer's disease, 10 cases of similarly confirmed senile dementia and 10 cases of mentally normal people. Alzheimer's neurofibrillary tangles were not observed at all in Alzheimer's disease and in the conrol group. A very small number of them were found in the intermediolateral cell, posterior column cell, anterolateral cell, and anteromedian cell groups in three cases of senile dementia. The deposition of lipofuscin was high in the anterolateral and posterolateral cell groups and nucl. dorsalis in all of the cases of Alzheimer's diseases, senile dementia and the control group. It is worthy of note that the Alzheimer's group, for its age, showed a relatively greater amount of lipofuscin.


Effect of unilateral nephrectomy on urinary angiotensinogen levels in living kidney donors: 1 year follow-up study.
Urinary angiotensinogen (uAGT) has recently been proposed as a marker of kidney injury and activated intrarenal renin-angiotensin system. We investigated the effects of living donor nephrectomy on uAGT levels, blood pressure, estimated glomerular filtration rate, proteinuria and compensatory hypertrophy in the remaining kidney of living kidney donors. Twenty living kidney donors were included in the study and followed for 1 year. uAGT levels were measured with enzyme-linked immunosorbent assay preoperatively and postoperatively at the 15th day, 1, 6 and 12 months. Four donors were excluded from the study due to lack of data. The mean baseline estimated glomerular filtration rate was 98 ± 15 ml/min/1.73 m². Serum creatinine, uAGT/creatinine, uAGT/protein levels were higher and estimated glomerular filtration rate was lower than baseline values at all time periods. Urinary protein/creatinine levels increased after donor nephrectomy, but after 6 months they returned to baseline values. Renal volume increased after nephrectomy, but these changes did not show any correlation with uAGT/creatinine, uAGT/protein, estimated glomerular filtration rate or systolic/diastolic blood pressures. uAGT/creatinine at 6 months and urinary protein/creatinine ratio at 12 months showed a positive correlation ( P=0.008, r=0.639). After donor nephrectomy, increasing uAGT levels can be the result of activation of the intrarenal renin-angiotensin system affecting the compensatory changes in the remaining kidney. The long-term effects of increased uAGT levels on the remaining kidney should be examined more closely in future studies.


The 20-Year Trajectory of Marital Quality in Enduring Marriages: Does Equity Matter?
I examine the trajectory of marital quality as a function of relationship equity with data from a six-wave panel study of 704 married respondents between 1980 and 2000. Reporting that one "gives more" to the marriage (subjective underbenefit) is more likely for women than men at any given marital duration. Respondent's relative contribution to income, paid labor, housework, and health (objective underbenefit) raises this probability for women of average religiosity. For the more religious, objective underbenefit has no effect on women's sense of underbenefit, but reduces men's sense of underbenefit. Objective underbenefit lowers women's, but raises men's, marital quality, at any marital duration. The relevance of equity was not diluted by the passage of time in marriage.


Multiparametric MRI for the Diagnosis of Tumor Type in Patients Suspicious of Inner Gland Prostate Cancer.
The current study aimed to evaluate multiparametric MRI for the diagnosis of type of tumor (benign ormalignant) in patients suspicious of inner gland prostate cancer. This cross-sectional study was conducted on 44 consecutive patients with a clinicalimpression of prostate cancer who were referred to the MRI department of Payambaran Hospital, Tehran, Iranfor confirmative diagnostic evaluation. Cases suspected of tumor relapse and those who previously underwenttreatment for prostate cancer were excluded. Multiparametric MRI was performed for every patient by using a 1.5Tesla device with an integrated endorectal and pelvic-phased array coil. All patients subsequently underwent MRItransrectalultrasound fusion biopsy. The diagnostic value of each sequence was then investigated individually andin combination with other techniques by comparing the results with histological findings from MRI-TRUS fusionbiopsy. Among the techniques, T2-weighted imaging (T2W) had the highest sensitivity and specificity whiledynamic contrast enhanced (DCE) technique had the least. Diffusion-weighted imaging (DWI) and magnetic resonancespectroscopy (MRS) had a similar sensitivity and specificity and did not significantly differ from T2W.Adding functional techniques to T2W did not improve diagnostic indices compared to T2W alone. Quantitativeevaluation of apparent diffusion coefficient (ADC), DWI, and MRS showed that all techniques were able to differentiatebetween benign and malignant tumors. However, the quantitative combination of these sequences decreaseddiagnostic performance. T2W is the best technique for the diagnosis of type of tumor in terms of benignancy or malignancyin patients suspicious of inner gland prostate cancer. Adding functional imaging measurements to T2W does notimprove its diagnostic value.


Ship-plume sulfur chemistry: ITCT 2K2 case study.
The ship-plume sulfur chemistry was investigated for the ITCT 2K2 (Intercontinental Transport and Chemical Transformation 2002) ship-plume experiment, using the ship-plume photochemical/dynamic model developed in this study. In order to evaluate the performance of the model, the model-predicted mixing ratios of SO2 and H2SO4 were compared with those observed. From these comparisons, it was found that the model-predicted levels were in reasonable agreements with those observed (0.56≤R≤0.71), when the pH of sea-salt particles (pHss) was ≤~6.5. The ship-plume equivalent lifetimes of SO2 (τ(eq)(SO(2))) were also estimated/investigated for this particular ship-plume case. The magnitudes of τ(eq)(SO(2)) were found to be controlled by two main factors: (i) the mixing ratios of in-plume hydroxyl radicals (OH) and (ii) pHss. The former is governed primarily by stability conditions of the marine boundary layer (MBL), when the ship NOx emission rate is fixed. The latter determines if the heterogeneous oxidation of dissolved SO2 occurs via reaction with hydrogen peroxide (H2O2, when pHss<6.5) or with ozone (O3, when pHss>6.5). According to the multiple ship-plume photochemical/dynamic model simulations, the estimated τ(eq)(SO(2)) over the entire ship plumes ranged from 10.32 to 14.32 h under moderately stable (E) to stable (F) MBL conditions. These values were clearly shorter than the background SO2 lifetime (τ(b)(SO(2))) of 15.18-23.20 h. In contrast, τ(eq)(SO(2)) was estimated to be 0.33 h when the pHss remained at ~8.0 (a rather unlikely case). In addition, the SO2 loss budget was further analyzed to estimate the influences of the two main factors on the ship-plume sulfur chemistry. The changes in the loss budget with pHss clearly showed a shift in the dominant SO2 loss processes from heterogeneous SO2 conversion (when pHss>~6.5) to the gas-phase oxidation of SO2 by OH (when pHss<~6.5).


WICID framework version 1.0: criteria and considerations to guide evidence-informed decision-making on non-pharmacological interventions targeting COVID-19.
Public health decision-making requires the balancing of numerous, often conflicting factors. However, participatory, evidence-informed decision-making processes to identify and weigh these factors are often not possible- especially, in the context of the SARS-CoV-2 pandemic. While evidence-to-decision frameworks are not able or intended to replace stakeholder participation, they can serve as a tool to approach relevancy and comprehensiveness of the criteria considered. To develop a decision-making framework adapted to the challenges of decision-making on non-pharmacological interventions to contain the global SARS-CoV-2 pandemic. We employed the 'best fit' framework synthesis technique and used the WHO-INTEGRATE framework as a starting point. First, we adapted the framework through brainstorming exercises and application to case studies. Next, we conducted a content analysis of comprehensive strategy documents intended to guide policymakers on the phasing out of applied lockdown measures in Germany. Based on factors and criteria identified in this process, we developed the WICID (WHO-INTEGRATE COVID-19) framework version 1.0. Twelve comprehensive strategy documents were analysed. The revised framework consists of 11+1 criteria, supported by 48 aspects, and embraces a complex systems perspective. The criteria cover implications for the health of individuals and populations due to and beyond COVID-19, infringement on liberties and fundamental human rights, acceptability and equity considerations, societal, environmental and economic implications, as well as implementation, resource and feasibility considerations. The proposed framework will be expanded through a comprehensive document analysis focusing on key stakeholder groups across the society. The WICID framework can be a tool to support comprehensive evidence-informed decision-making processes.


Involvement of cyclooxygenase- and lipoxygenase-mediated conversion of arachidonic acid in controlling human vascular smooth muscle cell proliferation.
We observed that the growth of human umbilical artery smooth muscle cells was inhibited by the phospholipase A2 inhibitors p-bromophenacylbromide and mepacrine. These findings suggest that fatty acid metabolism might be integrated in the control mechanism of vascular smooth muscle cell proliferation. To identify eicosanoids possibly involved in this process, we studied both the metabolism of arachidonic acid of these cells in more detail and the effect of certain arachidonic acid metabolites on smooth muscle cells growth. We found no evidence for the conversion of arachidonic acid via the lipoxygenase pathway. In contrast, arachidonic acid was rapidly converted via the cyclooxygenase pathway. The following metabolites were identified: prostaglandin E2 (PGE2), 6-keto-prostaglandin F1 alpha (6-k-PGF1 alpha), prostaglandin F2 alpha (PGF2 alpha), 12-hydroxyheptadecatrienoic acid (12-HHT) and 11-hydroxyeicosatetetraenoic acid (11-HETE). PGE2 was the major metabolite detected. Arachidonic acid metabolites were only found in the culture medium, not in the cell. After synthesis, 11-HETE was cleared from the culture medium. We have previously reported that PGE2 inhibits the serum-induced [3H]-thymidine incorporation of growth-arrested human umbilical artery smooth muscle cells. Here we show that also 11-HETE exerts this inhibitory property. Thus, our data suggests that human umbilical artery smooth muscle cells convert arachidonic acid only via the cyclooxygenase pathway. Certain metabolites produced by this pathway, including PGE2 and 11-HETE, may inhibit vascular smooth muscle cell proliferation.


Comparative study of lesions in the brain of rats exposed to heavy ions: accelerator and stratospheric flight research.
Irradiations of rat's brain with heavy ionized particles (12/6C, 291 Mev/nucleon, 100 to 300 ions/mm2) have been carried out at the Lawrence Berkeley Laboratory. Exposures were made with slowed ions which stopped within the brain as well as with more energetic particles which passed through. Histological examination of irradiated encephalons by optical microscopy showed zones of glial reaction and an increased number of darkly staining cells. By electron microscopy, intercellular edema, various alterations of nervous cells and macrophagy were observed, especially with stopped ions.


Effects of ultrasound irradiation on Au nanoparticles deposition on carbon-coated LiNi0.5Mn1.5O4 and its performance as a cathode material for Li ion batteries.
LiNi0.5Mn1.5O4 (LMNO) has attracted considerable attention as a Li-ion battery cathode material, owing to its high discharge voltage of 4.7 V (vs. Li/Li+) and high energy density. However, the electronic conductivity of LMNO is low, resulting in a low discharge capacity at high current density. To overcome this limitation, we deposited Au nanoparticles (NPs), which have a high conductivity and chemical stability at high battery voltages, on carbon-coated LMNO (LMNO/C) using ultrasound irradiation. Consequently, Au NPs that are ∼16 nm in size were deposited on LMNO/C, and ultrasound irradiation was reported to disperse the NPs on LMNO/C more effectively than stirring. Furthermore, the deposition of Au NPs on LMNO/C using ultrasound irradiation improved its electronic conductivity, which is related to an increase in the discharge capacity due to the reduction of Ni4+ to Ni2+ in LMNO/C at a high current density.


The epitaxy of 2D materials growth.
Two dimensional (2D) materials consist of one to a few atomic layers, where the intra-layer atoms are chemically bonded and the atomic layers are weakly bonded. The high bonding anisotropicity in 2D materials make their growth on a substrate substantially different from the conventional thin film growth. Here, we proposed a general theoretical framework for the epitaxial growth of a 2D material on an arbitrary substrate. Our extensive density functional theory (DFT) calculations show that the propagating edge of a 2D material tends to align along a high symmetry direction of the substrate and, as a conclusion, the interplay between the symmetries of the 2D material and the substrate plays a critical role in the epitaxial growth of the 2D material. Based on our results, we have outlined that orientational uniformity of 2D material islands on a substrate can be realized only if the symmetry group of the substrate is a subgroup of that of the 2D material. Our predictions are in perfect agreement with most experimental observations on 2D materials' growth on various substrates known up to now. We believe that this general guideline will lead to the large-scale synthesis of wafer-scale single crystals of various 2D materials in the near future.


Chemokines driven ovarian cancer progression, metastasis and chemoresistance: Potential pharmacological targets for cancer therapy.
Ovarian cancer is a leading cause of death among women globally often characterized by poor prognosis and aggressive tumor growth. The therapeutic outcomes of ovarian cancer patients are majorly limited by the development of acquired chemo/radioresistance and the lack of targeted therapies. The tumor microenvironment (TME) comprises a diverse population of cells including adipocytes, fibroblasts, tumor cells, and immune cells which play an imperative role in promoting tumor growth, invasion, and malignant phenotypes of cancer cells. The cells present in TME secrete various inflammatory mediators including chemokines and cytokines, which regulate the tumor progression and metastasis. This review article highlights new insights about the general mechanisms associated with chemokines-mediated cell proliferation, inflammation, tumor initiation, progression, metastasis, chemoresistance, and immune evasion in ovarian cancer. We also discuss the microRNAs (miRNAs) regulating the oncogenic potential of chemokines. Overall, this is a comparatively less explored area that could provide important insights into ovarian cancer development and a promising avenue for targeted therapy of ovarian cancer.


Comparative efficacy of azithromycin versus clarithromycin in combination with beta-lactams to treat community-acquired pneumonia in hospitalized patients: a systematic review.
The objective was to compare the efficacy of azithromycin and clarithromycin in combination with beta-lactams to treat community-acquired pneumonia among hospitalized adults. Five databases (PubMed, Google Scholar, Trip, Medline, and Clinical Key) were searched to identify randomized clinical trials with patients exposed to azithromycin or clarithromycin in combination with a beta-lactam. All articles were critically reviewed for inclusion in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seven clinical trials were included. The treatment success rate for azithromycin-beta-lactam after 10 to 14 days was 87.55% and that for clarithromycin-beta-lactam after 5 to 7 days of therapy was 75.42%. Streptococcus pneumoniae was commonly found in macrolide groups, with 130 and 80 isolates in the clarithromycin-based and azithromycin-based groups, respectively. The length of hospital stay was an average of 8.45 days for patients receiving a beta-lactam-azithromycin combination and 7.25 days with a beta-lactam-clarithromycin combination. Macrolide inter-class differences were noted, with a higher clinical success rate for azithromycin-based combinations. However, a shorter length of hospital stay was achieved with a clarithromycin-beta-lactam regimen. Thus, a macrolide combined with a beta-lactam should be chosen using susceptibility data from the treating facility.


Overexpression of NIMA-related kinase 2 is associated with poor prognoses in malignant glioma.
Eleated expression of NIMA-related kinase 2 (NEK2) was frequently observed in a variety of malignant cancers, and it appears to be involved in the initiation, maintenance, progression, metastasis of cancer and is positively associated with poor prognosis. We sought to investigate NEK2 expression and its predictive roles in malignant gliomas, and study the correlation of NEK2 protein expression with proliferation, clinical parameters, overall survival and some other parameters. We investigate NEK2 protein expression in 99 samples of malignant gliomas, including 35 WHO grade II, 22 grade III, and 42 grade IV gliomas, by immunohistochemistry and western blot (n = 50). We then made correlative analysis of protein overexpression using the Kaplan-Meier method, Log rank test, and Cox proportional-hazards model analysis. NEK2 protein was overexpressed in malignant gliomas, but not in normal brain tissues. Overexpression of NEK2 correlated with malignancy, proliferation and adverse overall survival in gliomas. Moreover, chemotherapy, resection extent and WHO grade also correlate with overall survival in gliomas. However, within WHO grade II glioma subgroup, NEK2 overexpression showed no impact on overall survival. The present study firstly reveals that NEK2 protein is widely overexpressed in gliomas. NEK2 overexpression correlates significantly with malignancy (WHO grades), proliferation (Ki-67) and prognosis in malignant gliomas. NEK2 is a potential gene therapy target and prognostic indicator.


Heartbeat evoked potentials mirror altered body perception in depressed patients.
Awareness of stimuli originating inside of the body (interoceptive awareness) is thought to have an impact on psychopathology. The aim of the present study was to analyze whether heartbeat perception accuracy is reduced in depressed patients. Furthermore, we investigated whether putative differences are reflected in heartbeat-evoked potentials. We assessed the heartbeat perception score in 16 depressed patients and in matched healthy controls. A 63-channel EEG was recorded while participants counted pseudo-randomly presented target tones or heartbeats during a fixed number of cardiac cycles. ECG R-waves served as the trigger for EEG averaging. The cardiac-field artifact was minimized using independent component analysis and current-source density. Behaviorally, the depressed sample showed less accurate heartbeat perception in comparison to the control group (p=.011). The two groups also demonstrated psychophysiological differences, showing that heartbeat-evoked potentials were significantly reduced in depressed patients. Our results suggest that heartbeat evoked potentials are objective markers of altered bodily awareness. Reduced interoception during depression may be linked to alexithymia, as well as to both decreased capacity for decision-making and for cognitive processing. It may be helpful to practice interoceptive awareness to improve depressive symptoms, for example by practicing meditation.


Kappa statistics in the assessment of observer variation: the significance of multiple observers classifying ankle fractures.
Studies using kappa statistics have been conducted with a varied but limited number of observers. The aim of this study was to evaluate the significance of multiple observers on kappa as a measure of observer variation. One hundred orthopedic specialists were asked to assess a random sample of ten sets of standard radiographs of 94 consecutive patients with ankle fractures. The observers were randomly allocated into four groups, which again were divided into subgroups with an increasing number of observers. Random subgroups of three observers revealed kappa values from 0.20 to 0.64 in the Lauge-Hansen and 0.27 to 0.90 in the Weber classification system. With an increasing number of observers in the subgroups, kappa stabilizes around a mean value, indicating that the sampling variation and standard error decrease. The standard error found in this study makes kappa questionable as a measure for agreement among a small number of observers. Thus, kappa values obtained for a given diagnostic tool at one department are not directly comparable with results from other departments. We conclude that kappa cannot stand alone as a simple measure of observer variation.


Glial heterotopia of the orbit and extranasal region: an unusual entity.
Glial heterotopia or the occurrence of isolated non-teratomatous extracranial glial tissue is rare. Most of the reported cases of this entity arise in the nose. Herein a rare case of heterotopic glial tissue in the orbit and extranasal region without bony defect is described.


Determination of lysozyme activity by fluorescence polarization in rheumatoid synovial fluids and release of lysozyme from polymorphonuclear leukocytes by chemotactic factors.
A new method for the measurement of lysozyme activity, which is rapid, quantitative and sensitive, was established and applied to clinical material obtained from arthritis patients. The method is based on fluorescence polarization with the use of fluorescein isothiocyanate-labeled peptidoglycan. Using this method, we found that the synovial fluids obtained from rheumatoid arthritis contained more lysozyme activity than similar samples from osteoarthritis patients (P less than 0.001). Furthermore, we found that chemotactic factors and lysozyme-depleted rheumatoid synovial fluids could induce the release of lysozyme from human polymorphonuclear leukocytes in vitro. It is therefore suggested that lysozyme present in rheumatoid synovial fluids may derive in part from polymorphonuclear leukocytes and the action of chemotactic factor(s) within the fluids.


One model of healthcare provision lessons learnt through clinical governance.
Clinical Governance describes a systematic approach to maintaining and improving the quality of patient care. Risk management includes a themes analysis of clinical incidents and positive interventions with the resulting information disseminated to staff through personal performance plans, and publication and development training workshops. Our model of healthcare provision utilises doctors, nurses and paramedics to assess individuals in custody and this paper discusses the implementation of clinical risk management within this setting. A description of the model of healthcare provision, together with a themes analysis was undertaken for all clinical incidents received by the clinical team. Each incident receives an individual response and is discussed within the clinical risk management committee. From the review of each event, learning outcomes are identified and the information captured on a database. The information is analysed for reoccurring themes and further measures are introduced to ensure a high standard of healthcare provision to all counties. Of the 86,184 patient/detainee episodes from 11 county forces, from January 2009-December 2009, 159 clinical incidents and positive interventions were generated. These were categorised into Clinical Near Misses--39, Prescribing issues--38, Health and Safety matters--13, Organisational matters--23, Positive Interventions--21 and Professional issues--25. Risk management, with a regular review of clinical incidents is an essential part of clinical governance especially when working in a multidisciplinary team providing safe and effective custody healthcare. This analysis contributes to the knowledge base in clinical forensic medicine and supports the importance of identifying educational requirements for staff, working in a multiagency partnership and continuous monitoring of the quality of care for detainees.


CD69 serves as a potential diagnostic and prognostic biomarker for hepatocellular carcinoma.
The prevalence and mortality of hepatocellular carcinoma (HCC) are still increasing. This study aimed to identify potential therapeutic targets related to patient prognosis. Data were downloaded from TCGA, GSE25097, GSE36376, and GSE76427 datasets. Differential analysis and enrichment analysis were performed in HCC. Cell deaths were evaluated, and least absolute shrinkage and selection operator regression (LASSO) regression was analyzed to screen candidate genes. Additionally, immune cell infiltration in HCC was assessed. We identified 4088 common DEGs with the same direction of differential expression in all four datasets, they were mainly enriched in immunoinflammation and cell cycle pathways. Apoptosis was significantly suppressed in HCC in GSEA and GSVA. After LASSO regression analysis, we screened CD69, CDC25B, MGMT, TOP2A, and TXNIP as candidate genes. Among them, CD69 significantly influenced the overall survival of HCC patients in both TCGA and GSE76427. CD69 may be a protective factor for outcome of HCC patients. In addition, CD69 was positive correlation with T cells and CD3E. CD69, CDC25B, MGMT, TOP2A, and TXNIP were potential diagnostic and prognostic target for HCC, especially CD69.


Anesthesia for functional endoscopic sinus surgery: a review.
Functional endoscopic sinus surgery has become one of the most common head and neck procedures performed. Proper anesthetic management is essential for a successful outcome. Different anesthesia techniques are discussed that include: local versus general anesthesia, LMA versus ETT, inhaled anesthesia versus TIVA. The anesthetic plan should be tailored taking into consideration patient comorbidities, the surgeon and anesthesiologist experience, and individual preference. Specific anesthetic goals are to ensure the best possible surgical field and stable cardiovascular and respiratory status during the surgery, emergence of anesthesia, and upon recovery.


Cognitive Dysfunctions in Patients with Alcohol Dependence Syndrome in a Tertiary Hospital in Kathmandu.
Alcohol dependence is a chronic disorder, accompanied by neuropsychological deficits. Patients with alcohol dependence were evaluated to identify the cognitive dysfunctions. The study followed descriptive design and recruited participants (N=62) from inpatient services of the Department of Psychiatry and Mental Health by convenient sampling. Participants were evaluated with the Severity of Alcohol Dependence Questionnaire, Frontal Assessment Battery and PGI Memory Scale for the severity of alcohol dependence, executive impairments and memory dysfunctions respectively once they had completed alcohol detoxification. Total duration of alcohol consumption was 13.93 ± 8.74 years, period of dependence was 2.97 ± 2.23 years and 56.5% had moderate level of dependence. 33.9% of the participants had executive impairments particularly in conceptualization, programming and mental flexibility. 38% of variance in executive dysfunction was explained by illness variables, where period of alcohol dependence and education were significant predictors. 54.8% had significant memory dysfunction particularly in visual retention, remote memory, verbal retention of dissimilar pairs and delayed recall. Memory dysfunction differed significantly among the age groups (F=10.22, p<0.01) and age was a significant predictor (β=.542, p<0.001). 19% variance in memory dysfunction was explained by illness variables, where duration of alcohol consumption was a significant predictor (β = .485, p<0.01). Findings indicate that cognitive dysfunctions are prevalent among patients with alcohol dependence. Hence, routine neuropsychological assessment is of particular importance for early detection and remediation of underlying deficits, which completes the treatment of alcohol dependence.


Characterisation and utilization of steel industry waste sludge as heterogeneous catalyst for the abatement of chlorinated organics by advanced oxidation processes.
Catalytic advanced oxidation processes (AOPs) utilising UV irradiation have been reported to be highly efficient for the degradation of recalcitrant compounds. The focus of present study was to evaluate the potential of steel industry waste as an alternative to homogenous iron salts often used in AOPs. Iron rich sludge from effluent treatment plant (ETP) of a steel industry was subjected to acid washing and acid washing followed by calcination before using as catalyst for the oxidative removal of chlorinated organics present in synthetic and simulated bleaching effluents. The maximum total organic carbon removals of 64% and 25% from 4-chlorophenol solution and simulated pulp bleaching effluent, respectively were observed during photo-catalytic oxidation with acid washed steel sludge at stoichiometric H2O2 dose after 2 h reaction (catalyst dose = 1 g/L, and pH = 4.4). Low iron leaching (<2%) was observed from the catalyst even in acidic conditions and it could be reused twice without significant loss of catalytic activity.


[Cost-analysis of viscosupplementation treatment with hyaluronic acid in candidate knee replacement patients with osteoarhritis].
A high percentage of knee osteoarthritis finally need a knee replacement. Previous treatments used including viscosupplementation with hyaluronic acid can delay the knee replacement. The objective of this study was to estimate the economic impact in the short, medium and long term of the knee replacement delay, by conducting a budget impact analysis of the incorporation of viscosupplementation to the treatment of knee osteoarthritis. From the data of patients treated at a specialized Knee Osteoarthritis Unit we built a discrete event simulation model that reproduced the progress of patients, as it could represent changes in the health status of an individual and their interaction with the system. The model allowed the number of prostheses and replacements performed each year to be calculated in a population including 1,000 patients each year according to the use of viscosupplementation. The budget impact analysis was estimated for 10 years by adding the cost of each treatment. A total of 224 patient candidates to receive a knee replacement were studied. The viscosupplementation use delayed the need to perform the knee replacement by 2.67 years The budgetary impact would lead to net savings during the 10 years. However, it is much greater in the earlier years. The sum of the savings in the first three years would be 36 million euros. The study concludes that the use of viscosupplementation reduced the economic burden of knee osteoarthritis in the health system as a result of delayed knee replacement. The simulation model enabled the economic impact in both the short and long term to be analysed.


Plasma anti-Müllerian hormone as a predictive endocrine marker to select Bos taurus (Holstein) and Bos indicus (Nelore) calves for in vitro embryo production.
This study evaluated the association between plasma anti-Müllerian hormone (AMH) concentrations and in vitro embryo production in Bos indicus (Nelore; experiment 1) and Bos taurus (Holstein; experiment 2) calves superstimulated or not with 140 mg of porcine follicle-stimulating hormone (pFSH; 4 decreasing doses twice daily). Oocytes were recovered from calves aged 2 to 4 mo after receiving gonadotropin stimulation (Nelore, n = 15; Holstein, n = 12) or not (Nelore, n = 15; Holstein, n = 12). Cycling heifers formed a positive control group (n = 15 for Nelore [aged 18-24 mo], n = 10 for Holstein [aged 14-16 mo]). All the calves underwent laparoscopic ovum pickup, and cycling heifers underwent a regular transvaginal ultrasound-guided ovum pickup for oocyte recovery. Immediately before oocyte retrieval, blood samples were taken for subsequent AMH determination (ng/mL). Regardless of the genetic group, calves that received pFSH (3.6 ± 1.1 in Nelore and 4.6 ± 1.2 in Holstein) or did not receive pFSH (3.2 ± 1.0 in Nelore and 2.5 ± 0.8 in Holstein) had greater plasma AMH concentrations (P = 0.01 in Nelore and P = 0.003 in Holstein) than cycling heifers (1.1 ± 0.2 in Nelore and 0.6 ± 0.07 in Holstein). AMH concentrations in calves with or without pFSH were similar in both genetic groups (3.6 ± 1.1 vs 3.2 ± 1.0 in Nelore; 4.6 ± 1.2 vs 2.5 ± 0.8 in Holstein). In calves, positive correlations were observed between plasma AMH concentrations and the numbers of follicles >2 mm (r = 0.86, P < 0.0001 in Nelore; r = 0.78, P < 0.0001 in Holstein), cumulus-oocyte complexes (COCs) retrieved (r = 0.91, P < 0.0001 in Nelore; r = 0.82, P < 0.0001 in Holstein), COCs cultured (r = 0.71, P < 0.0001 in Nelore; r = 0.79, P < 0.0001 in Holstein), and blastocysts produced (r = 0.62, P = 0.0003 in Nelore; r = 0.58, P = 0.009 in Holstein), and these results were independent of pFSH treatment. In conclusion, calves had greater plasma AMH concentrations than cycling heifers. In addition, treatment with pFSH did not influence AMH concentrations in calves, regardless of the genetic group. More importantly, plasma AMH concentrations were positively correlated with the antral follicle population and the number of COCs retrieved, COCs cultured, and blastocysts produced in B indicus and B taurus calves. Therefore, AMH is a promising tool for selecting oocyte donor calves to maximize results during in vitro embryo production.


Experimental hyphema clearance in rabbits. Drug trials with 1% atropine and 2% and 4% pilocarpine.
The effect of topical 1% atropine sulfate, 2% pilocarpine hydrochloride, and 4% pilocarpine hydrochloride on the clearance rate of RBCs labeled with chromium 51 (51Cr) that were injected into the anterior chamber of rabbits was determined by monitoring sequential radioactivity counts. Counts were made directly over the anterior chamber. One eye of each animal was treated with either 1% atropine, 2% pilocarpine, or 4% pilocarpine, and the other eye served as a control. None of these drugs significantly altered the clearance rate of 51Cr-labeled RBCs injected into the anterior chamber.


Compliance with wetland mitigation standards in the upper peninsula of Michigan, USA.
The United States has lost about half its wetland acreage since European settlement, and the effectiveness of current wetland mitigation policies is often questioned. In most states, federal wetland laws are overseen by the U.S. Army Corps of Engineers, but Michigan administers these laws through the state's Department of Environmental Quality (MDEQ). Our research provides insight into the effectiveness of the state's implementation of these laws. We examined wetland mitigation permit files issued in Michigan's Upper Peninsula between 2003 and 2006 to assess compliance with key MDEQ policies. Forty-six percent of files were out of compliance with monitoring report requirements, and forty-nine percent lacked required conservation easement documents. We also conducted site assessments of select compensatory wetland projects to determine compliance with MDEQ invasive plant species performance standards. Fifty-five percent were out of compliance. We found no relationship between invasive species noncompliance and past site monitoring, age of mitigation site, or proximity to roads. However, we found wetland restoration projects far more likely to be compliant with performance standards than wetland creation projects. We suggest policy changes and agency actions that could increase compliance with wetland restoration and mitigation goals.


Vernakalant for Rapid Cardioversion of Recent-Onset Atrial Fibrillation: Results from the SPECTRUM Study.
Rapid restoration of sinus rhythm using pharmacological cardioversion is commonly indicated in patients with symptomatic recent-onset atrial fibrillation (AF). The objectives of this large, international, multicenter observational study were to determine the safety and effectiveness of intravenous (IV) vernakalant for conversion of AF to sinus rhythm in daily practice. Consenting patients with symptomatic recent-onset AF (< 7 days) treated with IV vernakalant were enrolled and followed up to 24 h after the last infusion or until discharge, in order to determine the incidence of predefined serious adverse events (SAEs) and other observed SAEs and evaluate the conversion rate within the first 90 min. Overall, 2009 treatment episodes in 1778 patients were analyzed. The age of patients was 62.3 ± 13.0 years (mean ± standard deviation). Median AF duration before treatment was 11.1 h (IQR 5.4-27.0 h). A total of 28 SAEs occurred in 26 patients including 19 predefined SAEs, i.e., sinus arrest (n = 4, 0.2%), significant bradycardia (n = 11, 0.5%), significant hypotension (n = 2, 0.1%), and atrial flutter with 1:1 conduction (n = 2, 0.1%). There were no cases of sustained ventricular arrhythmias or deaths. All patients who experienced SAEs recovered fully (n = 25) or with sequelae (n = 1). Conversion rate to sinus rhythm was 70.2%, within a median of 12 min (IQR 8.0-28.0 min). This large multicenter, international observational study confirms the good safety profile and the high effectiveness of vernakalant for the rapid cardioversion of recent-onset AF in daily hospital practice.


Real-World Effectiveness of Nirmatrelvir/Ritonavir on Coronavirus Disease 2019-Associated Hospitalization Prevention: A Population-based Cohort Study in the Province of Quebec, Canada.
Nirmatrelvir/ritonavir has shown to reduce COVID-19 hospitalization and death before Omicron, but updated real-world evidence studies are needed. This study aimed to assess whether nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization among high-risk outpatients. A retrospective cohort study of outpatients with SARS-CoV-2 between March 15 and 15 October 2022, using data from the Quebec clinico-administrative databases. Outpatients treated with nirmatrelvir/ritonavir were compared with infected ones not receiving nirmatrelvir/ritonavir using propensity-score matching. Relative risk (RR) of COVID-19-associated hospitalization within 30 days was assessed using a Poisson regression. A total of 8402 treated outpatients were matched to controls. Regardless of vaccination status, nirmatrelvir/ritonavir treatment was associated with a 69% reduced RR of hospitalization (RR: .31; 95% CI: .28; .36; number needed to treat [NNT] = 13). The effect was more pronounced in outpatients with incomplete primary vaccination (RR: .04; 95% CI: .03; .06; NNT = 8), while no benefit was found in those with a complete primary vaccination (RR: .93; 95% CI: .78; 1.08). Subgroups analysis among high-risk outpatients with a complete primary vaccination showed that nirmatrelvir/ritonavir treatment was associated with a significant decrease in the RR of hospitalization in severely immunocompromised outpatients (RR: .66; 95% CI: .50; .89; NNT = 16) and in high-risk outpatients aged ≥70 years (RR: .50; 95% CI: .34; .74; NNT = 10) when the last dose of the vaccine was received at least 6 months ago. Nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization among incompletely vaccinated high-risk outpatients and among some subgroups of completely vaccinated high-risk outpatients.


Geomagnetic polarity change, volcanic maxima and faunal extinction in the South Pacific.
Studies of deep-sea sedimentary cores from Antarctic Pacific waters show that some volcanic maxima occurred when the geomagnetic polarity was changing. Upper mantle activity and geomagnetic polarity change may therefore be related. Coincidences of faunal extinction and geomagnetic polarity change may be explained by corresponding volcanically induced climatic changes.


The role of combined SNV and CNV burden in patients with distal symmetric polyneuropathy.
Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of genetic disorders of the peripheral nervous system. Copy-number variants (CNVs) contribute significantly to CMT, as duplication of PMP22 underlies the majority of CMT1 cases. We hypothesized that CNVs and/or single-nucleotide variants (SNVs) might exist in patients with CMT with an unknown molecular genetic etiology. Two hundred patients with CMT, negative for both SNV mutations in several CMT genes and for CNVs involving PMP22, were screened for CNVs by high-resolution oligonucleotide array comparative genomic hybridization. Whole-exome sequencing was conducted on individuals with rare, potentially pathogenic CNVs. Putatively causative CNVs were identified in five subjects (~2.5%); four of the five map to known neuropathy genes. Breakpoint sequencing revealed Alu-Alu-mediated junctions as a predominant contributor. Exome sequencing identified MFN2 SNVs in two of the individuals. Neuropathy-associated CNV outside of the PMP22 locus is rare in CMT. Nevertheless, there is potential clinical utility in testing for CNVs and exome sequencing in CMT cases negative for the CMT1A duplication. These findings suggest that complex phenotypes including neuropathy can potentially be caused by a combination of SNVs and CNVs affecting more than one disease-associated locus and contributing to a mutational burden.Genet Med 18 5, 443-451.


Fibrodysplasia ossificans progressiva: a clue from the fly?
Fibrodysplasia (myositis) ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by symmetrical congenital malformations of the blastemal anlage of the hands and feet and by progressive heterotopic chondrogenesis and ossification of the soft connective tissues. There is neither an established pathogenesis nor an effective treatment for this disabling disorder. We reevaluated the published data on the natural history of FOP and discovered an array of developmental gradients (characteristic patterns of disease expression) similar to developmental anomalies induced by pleiotropic mutations of the decapentaplegic (dpp) locus in Drosophila melanogaster. The protein encoded by the dpp locus is a member of the transforming growth factor-beta (TGF-beta) family of molecules. It shares 75% sequence homology with the c-terminal region of two recently cloned human bone morphogenetic proteins (BMP-2A, BMP-2B), also members of the TGF-beta family. The striking sequence identity across so large an evolutionary distance suggests that the BMP-2 genes in man and the dpp gene in the fly may be derived from a common ancestral gene. BMP is the only molecule discovered thus far that is capable of inducing endochondral ossification in vivo. Expression of endochondral bone formation is the basis for limb formation in embryogenesis, longitudinal bone growth in postnatal life, and local bone regeneration (fracture healing) following injury. We believe that FOP is a genetic disorder characterized by a disturbed developmental expression of this endochondral program and may represent a mutation resulting in a dominant gain of function. The developmental similarities between decapentaplegic in the fly and FOP in man suggest a useful model for the study of FOP. The use of such a model might be especially fruitful in suggesting a molecular basis for FOP.


Phishing website prediction using base and ensemble classifier techniques with cross-validation.
Internet or public internetwork has become a vulnerable place nowadays as there are so many threats available for the novice or careless users because there exist many types of tools and techniques being used by notorious people on it to victimize people somehow and gain access to their precious and personal data resulting in sometimes smaller. However, these victims suffer considerable losses in many instances due to their entrapment in such traps as hacking, cracking, data diddling, Trojan attacks, web jacking, salami attacks, and phishing. Therefore, despite the web users and the software and application developer's continuous effort to make and keep the IT infrastructure safe and secure using many techniques, including encryption, digital signatures, digital certificates, etc. this paper focuses on the problem of phishing to detect and predict phishing websites URLs, primary machine learning classifiers and new ensemble-based techniques are used on 2 distinct datasets. Again on a merged dataset, this study is conducted in 3 phases. First, they include classification using base classifiers, Ensemble classifiers, and then ensemble classifiers are tested with and without cross-validation. Finally, their performance is analyzed, and the results are presented at last to help others use this study for their upcoming research.


Early or Late-Life Treatment With Acarbose or Rapamycin Improves Physical Performance and Affects Cardiac Structure in Aging Mice.
Pharmacological treatments can extend the life span of mice. For optimal translation in humans, treatments should improve health during aging, and demonstrate efficacy when started later in life. Acarbose (ACA) and rapamycin (RAP) extend life span in mice when treatment is started early or later in life. Both drugs can also improve some indices of healthy aging, although there has been little systematic study of whether health benefits accrue differently depending on the age at which treatment is started. Here we compare the effects of early (4 months) versus late (16 months) onset ACA or RAP treatment on physical function and cardiac structure in genetically heterogeneous aged mice. ACA or RAP treatment improve rotarod acceleration and endurance capacity compared to controls, with effects that are largely similar in mice starting treatment from early or late in life. Compared to controls, cardiac hypertrophy is reduced by ACA or RAP in both sexes regardless of age at treatment onset. ACA has a greater effect on the cardiac lipidome than RAP, and the effects of early-life treatment are recapitulated by late-life treatment. These results indicate that late-life treatment with these drugs provide at least some of the benefits of life long treatment, although some of the benefits occur only in males, which could lead to sex differences in health outcomes later in life.


Roles of Wnt pathway genes wls, wnt9a, wnt5b, frzb and gpc4 in regulating convergent-extension during zebrafish palate morphogenesis.
The Wnt signaling pathway is crucial for tissue morphogenesis, participating in cellular behavior changes, notably during the process of convergent-extension. Interactions between Wnt-secreting and receiving cells during convergent-extension remain elusive. We investigated the role and genetic interactions of Wnt ligands and their trafficking factors Wls, Gpc4 and Frzb in the context of palate morphogenesis in zebrafish. We describe that the chaperon Wls and its ligands Wnt9a and Wnt5b are expressed in the ectoderm, whereas juxtaposed chondrocytes express Frzb and Gpc4. Using wls, gpc4, frzb, wnt9a and wnt5b mutants, we genetically dissected the Wnt signals operating between secreting ectoderm and receiving chondrocytes. Our analysis delineates that non-canonical Wnt signaling is required for cell intercalation, and that wnt5b and wnt9a are required for palate extension in the anteroposterior and transverse axes, respectively.


Relationship between dynamic fatigue crack propagation properties and viscoelasticity of natural rubber/silicone rubber composites.
In this paper, dynamic fatigue crack propagation properties of natural rubber/silicone rubber (NR/VMQ) composites are studied under constant tearing energy (G) input. Through dynamic fatigue crack growth testing, it is found that with the increase of VMQ fraction, NR/VMQ exhibits a lower crack growth rate (dc/dN). The viscoelastic parameters have been recorded in real-time during crack propagation, including the storage modulus E', loss factor tan δ, and loss compliance modulus J'', and their relationships with crack propagation behaviour have been established. The improved crack propagation resistance is attributed to the reduced J'', resulting from the synergistic effect of increased E' and decreased tan δ, and thus more energy dissipation occurred in the linear viscoelastic region in front of the crack tip, which consumed part of the energy for crack growth. Finally, good correlation between dc/dN and J'' could be successfully established.


Effects of carnosine on polyamine levels in red blood cells of patients with hypertonic discirculatory encephalopathy.
The levels of polyamines (putrescine, spermine, spermidine) in erythrocytes from patients with hypertonic discirculatory encephalopathy are reduced (by 37, 45, and 50%, respectively) in comparison with the corresponding parameters in the control group. Addition of carnosine to the treatment protocol for chronic brain ischemia normalized the content of putrescine and spermine. The mechanisms of carnosine influence on polyamine metabolism are discussed: trapping of acrolein, end-product of polyamine oxidation, and compensation of NMDA-receptor excitotoxicity.


Crystallization of a DNA duplex 15-mer containing unpaired bases: d(CGCGAAATTTACGCG).
Crystals of an almost self-complementary DNA 15-mer d(CGCGAAATTTACGCG) have been grown by the vapor diffusion technique at 4 degrees C. The space group is I222 with a = 37.3 A, b = 54.6 A and c = 104.8 A. Solution studies showed that the 15-mer forms a duplex with the extra adenine residue unpaired: (sequence; see text) Crystals are stable at 4 degrees C and are suitable for medium-resolution structural studies.


Synthesis, fungicidal activity, and 3D-QSAR of tetrazole derivatives containing phenyloxadiazole moieties.
In an effort to discover new agents with good fungicidal activities against CDM (cucumber downy mildew), a series of tetrazole derivatives containing phenyloxadiazole moieties were designed and synthesized. The EC50 values for fungicidal activities against CDM were determined. Bioassay results indicated that most synthesized compounds exhibited potential in vivo fungicidal activity against CDM. A CoMFA (comparative molecular field analysis) model based on the bioactivity was developed to identify some primary structural quality for the efficiency. The values of q2 and r2 for the established model were 0.791 and 0.982 respectively, which reliability and predict abilities were verified. Three analogues (q3, q4, q5) were designed and synthesized based on the model. All these compounds exhibited significant fungicidal activity on CDM with the EC50 of 1.43, 1.52, 1.77 mg·L-1. This work could provide a useful instruction for the further structure optimization.


Sleep deprivation and epilepsy.
This review summarizes the data for and against sleep deprivation as a facilitator of epileptic seizures and interictal epileptiform discharges. Much of these data are derived from clinical studies; however, basic science investigations are greatly needed to determine the influence of sleep deprivation on seizure susceptibility and neuronal function. Study of the effects of sleep deprivation on epilepsy may create a window of opportunity that could help decipher how seizures are triggered and facilitated, potentially providing an avenue for future interventions.


Prevalence and predictors of exclusive breastfeeding for the first six months of life among women in Halaba special woreda, Southern Nations, Nationalities and Peoples' Region/SNNPR/, Ethiopia: a community based cross-sectional study.
Exclusive breastfeeding is defined as feeding infants only breast milk, be it directly from breast or expressed, with no addition of any liquid or solids apart from drops or syrups consisting of vitamins, mineral supplements or medicine, and nothing else. Several studies have shown that exclusive breastfeeding for the first six months plays a great role in preventing morbidity and mortality. In Ethiopia, for example, mortality rates of infant and children younger than five years are high. Understanding the prevalence and predictors that influence exclusive breastfeeding in this is crucial to promoting the practice. To assess the prevalence and predictors of exclusive breastfeeding with in the first six months of life among women in Halaby special woreda, SNNPR (Southern Nations, Nationalities and Peoples' Region) Ethiopia. A community-based cross sectional study was conducted between November 2013 and January 2014 among women with infants aged less than 6 months and the sample size was 422 in Halaba special woreda, SNNPR (Southern Nations, Nationalities and Peoples' Region) Ethiopia. A random sampling technique was used in sampling the study subjects. Structured questionnaire was developed and adopted from EDHS 2011 and WHO standard and that all the variables to be assessed were incorporated. Data was entered and analyzed through using Epi Info 7 for Dos version 3.5.1 and Statistical Package for the Social Sciences (SPSS) software for windows version 20 respectively. The prevalence of exclusive breastfeeding was (70.5 %) and awareness of exclusive breastfeeding was (92.4 %). Antenatal follow up (AOR/Adjusted odds ratio = 1.9; 95 % CI, 1.05-3.6), postnatal follow up (AOR/Adjusted odds ratio = 2.2; 95 % CI, 1.25-3.87), initiation of breast feeding immediately within one hour (AOR/Adjusted odds ratio =3.8; 95 % CI, 2.4-6.2), attended formal school (AOR Adjusted odds ratio/=1.9;95 % CI,1.1-3.4), advice about exclusive breastfeeding (AOR Adjusted odds ratio/=6.3;95 % CI,1.3-30.9); and awareness about exclusive breastfeeding (AOR Adjusted odds ratio/= 8.2; 95 % CI 3.34-20), have significant association with exclusive breastfeeding. Strategies that target improving awareness among women at health facility and community level help to improve exclusive breastfeeding. In addition, promotion of EBF for working mothers through working environment recommended.


High-Density Lipoprotein Subclasses and Noncardiovascular, Noncancer Chronic Inflammatory-Related Events Versus Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis.
High-density lipoprotein (HDL) particles have properties beyond reverse cholesterol transport. We hypothesized that their protection extends to inflammation-related disease. The predictive value of HDL particle subclasses and inflammatory markers was studied for noncardiovascular, noncancer chronic inflammation-related death and hospitalization, and for incident cardiovascular disease (CVD). A multiethnic, multicenter, prospective observational study was conducted in 6475 men and women (aged 45 to 84 years) free of known CVD at baseline with median follow-up of 10.1 years. Fasting venous samples were analyzed for baseline lipid profile and lipoprotein particles. We focused on the HDL family of variables (small-, medium-, and large-diameter HDL particles and HDL cholesterol). Analyses identified the sum of small- plus medium-diameter HDL particles as important. Small- plus medium-diameter HDL particles were inversely associated with diagnostic code-based noncardiovascular, noncancer chronic inflammation-related death and hospitalization (n=1054) independent of covariates: relative risk per SD 0.85 (95% CI: 0.79 to 0.91, P<0.0001). Small- plus medium-diameter HDL particles were also associated with adjudicated fatal and nonfatal coronary heart disease events (n=423): relative risk per SD 0.88 (95% CI 0.77 to 0.98, P=0.02). Small- plus medium-diameter HDL particles are an independent predictor for noncardiovascular, noncancer chronic inflammation-related death and hospitalization and for coronary heart disease events in subjects initially free of overt CVD. These findings support the hypothesis that smaller HDL particles of diameter <9.4 nm have anti-inflammatory properties in the general population.


Antibacterial activity of Aquilaria crassna leaf extract against Staphylococcus epidermidis by disruption of cell wall.
Aquilaria crassna Pierre ex Lecomte has been traditionally used in Thailand for treatment of infectious diseases such as diarrhoea and skin diseases for a long time. The main objectives of this study were to examine antibacterial activity of the Aquilaria crassna leaf extract against Staphylococcus epidermidis and its underlying mechanism. The antioxidant activity and acute toxicity were studied as well. Antioxidant activities were examined by FRAP, ABTS and DPPH scavenging methods. Antibacterial activity was conducted using disc diffusion assay and the minimum inhibitory concentration (MIC) was determined by dilution method. The minimum bactericidal concentration (MBC) was reported as the lowest concentration producing no growth of microbes in the subcultures. Morphological changes of the microbe were observed by scanning electron microscopy, while an inhibitory effect on biofilm formation was evaluated by phase contrast microscopic analysis. Bacterial cell wall integrity was assessed by transmission electron microscopy. Acute toxicity was conducted in accordance with the OECD for Testing of Chemicals (2001) guidelines. The extract exhibited considerable antioxidant activity. Staphylococcus epidermidis was susceptible to the extract with the MIC and MBC of 6 and 12 mg/ml, respectively. The extract caused swelling and distortion of bacterial cells and inhibited bacterial biofilm formation. Rupture of bacterial cell wall occurred after treated with the extract for 24 h. Acute toxicity test in mice showed no sign of toxicity or death at the doses of 2,000 and 15,000 mg/kg body weight. The aqueous extract of Aquilaria crassna leaves possesses an in vitro antibacterial activity against Staphylococcus epidermidis, with no sign of acute oral toxicity in mice, probably by interfering with bacterial cell wall synthesis and inhibiting biofilm formation.


Lewis Acidic Boranes, Lewis Bases, and Equilibrium Constants: A Reliable Scaffold for a Quantitative Lewis Acidity/Basicity Scale.
A quantitative Lewis acidity/basicity scale toward boron-centered Lewis acids has been developed based on a set of 90 experimental equilibrium constants for the reactions of triarylboranes with various O-, N-, S-, and P-centered Lewis bases in dichloromethane at 20 °C. Analysis with the linear free energy relationship log KB =LAB +LBB allows equilibrium constants, KB , to be calculated for any type of borane/Lewis base combination through the sum of two descriptors, one for Lewis acidity (LAB ) and one for Lewis basicity (LBB ). The resulting Lewis acidity/basicity scale is independent of fixed reference acids/bases and valid for various types of trivalent boron-centered Lewis acids. It is demonstrated that the newly developed Lewis acidity/basicity scale is easily extendable through linear relationships with quantum-chemically calculated or common physical-organic descriptors and known thermodynamic data (ΔH BF 3 ). Furthermore, this experimental platform can be utilized for the rational development of borane-catalyzed reactions.


Cocultured porcine granulosa cells respond to excess non-esterified fatty acids during in vitro maturation.
Non-esterified fatty acids (NEFAs) are one of the main lipid components of follicular fluid at concentrations that depend on circulating levels. Elevated levels of NEFAs impair oocyte quality, development potential, and may subsequently influence the metabolism and reproductive fitness of offspring. Granulosa cells (GCs) are the follicular cells that are closely communicating with the oocyte. However, the responses of GCs exposed to high levels of NEFAs when cocultured with cumulus-oocyte complexes (COCs), and how they attenuate the negative effects of NEFAs on oocytes, are unclear. To better understand this protective effect, monolayers of porcine GCs were cocultured with COCs during in vitro maturation (IVM) in the presence of elevated levels of NEFAs. Genomic expression analysis was conducted to explore the responses of the GCs to the elevated levels of NEFAs. After limma algorithm analysis, 1,013 genes were differentially expressed between GCs cultured with and without elevated NEFAs. Among them, 438 genes were upregulated and 575 were downregulated. The differentially expressed genes were enriched in pathways related to metabolism, inflammation, and epithelial-mesenchymal transition. The pathways and upstream regulators suggested that the cocultured GCs responded to the elevated NEFAs with (1) inhibition of the transition from granulosa to luteal cell, (2) interactions of metabolism change, anti-inflammation, mitochondrial function, and cell transition, (3) intercommunication with cocultured COCs of anti-inflammatory factors.


The role of bivalent ions in the regulation of D-loop extension mediated by DMC1 during meiotic recombination.
During meiosis, programmed DNA double-strand breaks (DSBs) are repaired by homologous recombination. DMC1, a conserved recombinase, plays a central role in this process. DMC1 promotes DNA strand exchange between homologous chromosomes, thus creating the physical linkage between them. Its function is regulated not only by several accessory proteins but also by bivalent ions. Here, we show that whereas calcium ions in the presence of ATP cause a conformational change within DMC1, stimulating its DNA binding and D-loop formation, they inhibit the extension of the invading strand within the D-loop. Based on structural studies, we have generated mutants of two highly conserved amino acids - E162 and D317 - in human DMC1, which are deficient in calcium regulation. In vivo studies of their yeast homologues further showed that they exhibit severe defects in meiosis, thus emphasizing the importance of calcium ions in the regulation of DMC1 function and meiotic recombination.


Prescribing patterns of encounters in fourteen general practice clinics in rural Beijing: a cross-sectional study.
General practice clinics are the main primary care institutions providing ambulatory care in the rural areas of Beijing, rational use of medicines is crucial for the rural primary care system. This study investigated the prescribing patterns of general practice clinics in rural Beijing to provide a baseline for monitoring and promoting the rational use of medicines. We performed a cross-sectional study at 14 rural community health service centers in 6 non-central districts of Beijing sampled through a multistage approach, 85 general practitioners were selected from the 14 centers. Total 8500 prescriptions were derived by recording 100 consecutive patients of each the general practitioner. The World Health Organization drug use indicators and an additional indicator were adopted to assess the prescribing patterns. The median number of medicines per encounter was 2.0 (1.0, 2.0); the percentage of generics and essential medicines prescribed were 97.0 and 58.2%, respectively; the percentage of encounters with antibiotics prescribed was 15.1%; the percentage of encounters with injections prescribed was 3.7%; the percentage of encounters with traditional Chinese patent medicines prescribed was 52.5%; the median duration of consultation time was 6.0 (4.0, 10.0) minutes. The most frequently prescribed medicine was aspirin (low dose, 4.6%). The prescribing indicators were influenced by different patient characteristics, patients with new cooperative rural medical scheme were less likely to be prescribed with ≥3 medicines (OR 0.865), essential medicines (OR 0.812) and traditional Chinese patent medicines (OR 0.631), but were more likely to be prescribed with injections (OR 1.551) in the encounter. Patients with ≥3 problems were more likely to be prescribed with ≥3 medicines (OR 6.753), antibiotics (OR 2.875) and traditional Chinese patent medicines (OR 2.926) in the encounter. Most indicators in this study showed similar or fair performance in comparison with World Health Organization and domestic reports, except the percentage of medicines prescribed from the essential medicine list. Regular monitoring on the prescription quality of general practice clinics in rural Beijing should be maintained.


Arthroscopic management of recurrent synovial chondromatosis of the hip: a case report.
Synovial chondromatosis is a rare condition characterized by the chondral proliferation of synovium forming loose bodies which can lead to pain, swelling, and decreased range of movement of the affected joint. Here the authors report a case of eighteen years lady with recurrent hip synovial chondromatosis who was treated previously with hip arthrotomy and loose bodies removal and now she underwent arthroscopic loose bodies removal with partial synovectomy. In comparison to arthrotomy of the hip, arthroscopic management is a minimally invasive surgery that is associated with decreased postoperative pain, earlier improvement in range of motion, a shorter course of rehabilitation, and overall lower morbidity. Thus, the authors recommend arthroscopic removal of the loose bodies and partial synovectomy for the management of synovial chondromatosis of the hip.


The effect of prolonged steep head-down laparoscopy on the optical nerve sheath diameter.
Both the steep head-down position and pneumoperitoneum increase the intracranial pressure (ICP), and their combination for a prolonged period during laparoscopic radical prostatectomy (LRP) might influence the central nervous system homeostasis. Changes in optic nerve sheath diameter (ONSD) may reflect those in ICP. This study aims to quantify the change in ONSD in response to peritoneal CO2 insufflation and steep Trendelenburg position during LRP. ONSD was measured by ultrasound in 20 patients undergoing LRP and ten awake healthy volunteers. In patients, ONSD was assessed at baseline immediately after induction of general anesthesia in supine position, 10 and 60 min from baseline in a 25° head-down position during pneumoperitoneum, and after deflation of pneumoperitoneum with the patient supine at 0° angle. ONSD in controls was assessed at baseline with the patient lying supine, after 10 and 60 min of 25° head-down position, and 10 min after repositioning at 0° angle. ONSD increased significantly in both patients and controls (p < 0.0001) without between-group differences. The mean increase was 10.3% (95% CI 7.7-12.9%) in patients versus 7.5% (95% CI 2.5-12.6%) in controls (p = 0.28), and didn't affect the time to recovery from anesthesia. In the studied patients, with a limited increase of end-tidal CO2 and airway pressure, and low volume fluid infusion, the maximal ONSD was always below the cut-off value suspect for increased ICP. ONSD reflects the changes in hydrostatic pressure in response to steep Trendelenburg position, and its increase might be minimized by careful handling of general anesthesia.


Flecainide excretion in human breast milk.
Healthy human volunteers who intended not to breast feed were placed on a regimen of 100 mg oral flecainide every 12 hours for 5 1/2 days beginning 1 day after parturition. Milk and blood samples were collected during the dosing period and for 2 days after the last dose. Concentrations of flecainide in milk and plasma were assayed by HPLC. Apparent steady-state levels of flecainide in both milk and plasma were achieved in most cases by day 4 of the study. Highest daily average concentration of flecainide in milk ranged from 270 to 1529 ng/ml for the 11 subjects. Mean +/- SD milk to plasma flecainide ratios were 3.7 +/- 3.5, 3.2 +/- 2.3, 3.5 +/- 2.1, and 2.6 +/- 0.7 on study days 2, 3, 4, and 5, respectively. After the last dose of flecainide, peak milk levels of the drug occurred at 3 to 6 hours and then declined monoexponentially. The half-life for elimination of flecainide from milk was 14.7 +/- 3.5 hours and is very similar to the plasma elimination half-life of flecainide in healthy human subjects. The mean milk to plasma ratios for flecainide after the last dose were 2.3 +/- 1.0 and 2.9 +/- 1.1 at 24 and 48 hours after the dose, respectively. Based on the pharmacokinetics of flecainide in infants, the expected average steady-state plasma concentration of flecainide in a newborn infant consuming all of the milk production of its mother (approximately 700 ml/day) would not be expected to exceed about 62 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)