Comparative effectiveness of generic nifedipine versus Adalat long-acting nifedipine for hypertension treatment: A multi-institutional cohort study.
This retrospective multi-institutional database analysis aimed to evaluate the blood-pressure-lowering efficacy and clinical outcomes of a generic versus brand-name nifedipine for hypertension management. A total of 12 693 patients who were prescribed a generic or brand-name nifedipine between January 1, 2011, and December 31, 2018, were identified from the Chang Gung Research Database of Chang Gung Memorial Hospitals, Taiwan. Among them, 2112 (21.4%) were prescribed generic nifedipine. After propensity score matching, both the generic and brand-name groups consisted of 2102 patients. At a mean follow-up of 3 years, the changes in office systolic (p for interaction = .791) and diastolic blood pressure (p for interaction = .689) did not differ significantly between the patients who received the generic and the brand-name nifedipine. There was no significant difference between the two study groups regarding the composite of all-cause mortality, acute myocardial infarction, stroke, coronary revascularization, or hospitalization for heart failure (hazard ratio 0.98, 95% confidence interval 0.85-1.13; p = .774). In conclusion, the generic nifedipine was comparable to its brand-name counterpart regarding office blood pressure reduction and the composite cardiovascular outcome for the treatment of patients with hypertension.


A new species of the South East Asian genus Sarax Simon, 1892 (Arachnida: Amblypygi: Charinidae) and synonymization of Sarax mediterraneus Delle Cave, 1986.
A new species of the whip spider genus Sarax Simon, 1892 from Cebu Island in the Philippines is described: Sarax huberi sp. nov. With the description of this species, the diversity of the genus is increased to three species in the Philippines. Some additional data on their natural environment and their specific habitat are presented and compared with sibling species. The synonymization of Sarax mediterraneus Delle Cave, 1986 with Sarax buxtoni (Gravely, 1915) is carried out.


Prenatal exposure to drinking-water chlorination by-products, cytochrome P450 gene polymorphisms and small-for-gestational-age neonates.
Genetic susceptibility may modulate chlorination by-products (CBPs) effects on fetal growth, especially genes coding for the cytochrome P450 involved in the metabolism of CBPs and steroidogenesis. In a case-control study of 1432 mother-child pairs, we assessed the association between maternal and child single nucleotide polymorphisms (SNPs) within CYP1A2, CYP2A6, CYP2D6 and CYP17A1 genes and small-for-gestational-age neonates (SGA<10th percentile) as well as interaction between these SNPs and maternal exposure to trihalomethanes or haloacetic acids (HAAs) during the third trimester of pregnancy. Interactions were found between mother and neonate carrying CYP17A1 rs4919687A and rs743572G alleles and maternal exposure to total trihalomethanes or five regulated HAAs species. However, these interactions became non statistically significant after correction for multiple testing. There is some evidence, albeit weak, of a potential effect modification of the association between CBPs and SGA by SNPs in CYP17A1 gene. Further studies are needed to validate these observations.


Effects of duodenal osmotic loads on spontaneous meals in pigs.
Fourteen young Large White pigs were trained to press a panel switch to obtain reinforcements of food (FR 10-15). Duodenal injections (5 ml/kg) were made automatically via implanted catheters shortly after the beginning of every other meal 24 hours a day. Solutions of varying osmoconcentration and nutrient content were injected. Isosmotic solutions of glucose (5, 20 and 40%) and NaCl (0.9, 3.25 and 6.5%) equally depressed the size of ongoing meals in proportion to their hypertonicity. For example, 20% glucose and 3.25% NaCl depressed meal size to 62% of control, and 40% glucose and 6.5% NaCl to 34%. Xylose (33%) was less effective than its glucose osmotic equivalent. Tetracaine (0.5%) blocked most of the reduction of meal size. The reduced meal size was due to a decrease in meal duration. Neither rate of eating during the meal nor intermeal interval changed. The results support the hypothesis that a duodenal osmoreceptive system participates normally in the control of meal size.


A novel approach for automated alcoholism detection using Fourier decomposition method.
The identification of alcoholism is of prime importance because of its adverse effects on the central nervous system. Moreover, people suffering from alcoholism are susceptible to various health problems such as cardiomyopathy, immune system disorder, high blood pressure, cirrhosis, brain anomalies, and heart problems. This study presents a novel approach, based on Fourier theory, known as Fourier decomposition method (FDM) for automatic identification of alcoholism using electroencephalogram (EEG) signals. The FDM approach is employed to decompose EEG signals into a set of desired orthogonal components, commonly referred as Fourier intrinsic band functions (FIBFs), obtained by dividing the complete bandwidth of EEG signal under analysis into equal frequency bands. Time-domain features such as Hjorth parameters, kurtosis, inter-quartile range, and median frequency are extracted from FIBFs. To reduce the complexity, Kruskal-Wallis (KW) statistical test, is performed to adopt the most significant features. Simulation results are obtained using different classification methods, namely, k-nearest neighbor (kNN), support vector machine (SVM), and linear discriminant analysis (LDA). The proposed approach with the SVM classifier using radial basis function provides average accuracy of 99.98%, sensitivity of 99.99% and specificity of 99.97%. Performance is also tested in the presence of noise. Classification results highlight the superior performance of our method in comparison to existing works. The proposed scheme provides an efficient approach and can be employed in real-time alcoholism detection.


Longitudinal Immune Profiling of a Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection in a Solid Organ Transplant Recipient.
The underlying immunologic deficiencies enabling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection are currently unknown. We describe deep longitudinal immune profiling of a transplant recipient hospitalized twice for coronavirus disease 2019 (COVID-19). A 66-year-old male renal transplant recipient was hospitalized with COVID-19 March 2020 then readmitted to the hospital with COVID-19 233 days after initial diagnosis. Virologic and immunologic investigations were performed on samples from the primary and secondary infections. Whole viral genome sequencing and phylogenetic analysis revealed that viruses causing both infections were caused by distinct genetic lineages without evidence of immune escape mutations. Longitudinal comparison of cellular and humoral responses during primary SARS-CoV-2 infection revealed that this patient responded to the primary infection with low neutralization titer anti-SARS-CoV-2 antibodies that were likely present at the time of reinfection. The development of neutralizing antibodies and humoral memory responses in this patient failed to confer protection against reinfection, suggesting that they were below a neutralizing titer threshold or that additional factors may be required for efficient prevention of SARS-CoV-2 reinfection. Development of poorly neutralizing antibodies may have been due to profound and relatively specific reduction in naive CD4 T-cell pools. Seropositivity alone may not be a perfect correlate of protection in immunocompromised patients.


Can FLT3 inhibitors overcome resistance in AML?
The identification of FLT3 mutations across a range of the cytogenetic subgroups of AML has opened up the possibility of a targeted therapeutic approach with broad applicability. Four agents are currently in clinical trials, at least 3 of which have both sufficient activity against AML and sufficiently acceptable toxicity profiles to support continued efforts to refine their inclusion into therapeutic regimens for AML. Better understanding of the genetics of inherent and acquired resistance is needed to guide development of second-generation agents. Optimizing the integration of FLT3 inhibitor therapy with chemotherapy has the potential both to decrease toxicity and improve response.


Proteomic Analysis of Testicular Interstitial Fluid in Men with Azoospermia.
The primary microenvironment of the testis comprises testicular interstitial fluid (TIF) surrounding the seminiferous tubules and testicular interstitial tissue. The pathological alterations of germ and Sertoli cells could affect the TIF composition and might contain putative biomarkers for monitoring active spermatogenesis. We identified differentially expressed proteins in the TIF of patients with obstructive (OA) or nonobstructive (NOA) azoospermia to elucidate the underlying etiology of defective spermatogenesis. We prospectively enrolled nine patients, including three men with OA and six with NOA with (n = 3) and without (n = 3) successful sperm retrieval. Their TIF was collected during the testicular sperm extraction procedure. TIF was analyzed using liquid chromatography-tandem mass spectrometry to identify differentially expressed proteins specific to OA and NOA with or without successful sperm retrieval. The dysregulated protein was further validated using Western blotting. Among the 555 TIF proteins identified in NOA patients, 14 were downregulated relative to OA patients. These proteins participate in biological processes such as proteolysis, complement activation, and immune responses; complement and coagulation cascade pathways were also enriched. Furthermore, 68 proteins with significantly higher levels were identified in the TIF of NOA patients with successful sperm retrieval than in those with failed sperm retrieval; these are mainly implicated in oxidation-reduction processes. The expression of calreticulin, which can distinguish successful and failed testicular sperm retrieval in the NOA group, was validated by Western blotting. We provide the first scientific evaluation of TIF protein composition in men with azoospermia. These findings will help identify the physiological and pathological roles of each protein in regulating sperm production. Thus, our study underscores the potential of TIF in sperm retrieval biomarker discovery and would serve as a foundation for further studies to improve treatment strategies against azoospermia. Using a proteomic approach, we identified and analyzed the total protein content of testicular interstitial fluid in humans with defective spermatogenesis for the first time and discovered altered protein expression patterns in patients with nonobstructive azoospermia (NOA). Proteins related to oxidation-reduction processes were upregulated in NOA patients with successful sperm retrieval compared with those with failed sperm retrieval. This can aid the development of novel diagnostic tools for successful testicular sperm retrieval.


Three-year comparison of subcutaneous insulin pump treatment with multi-daily injections on HbA1c, its variability and hospital burden of children with type 1 diabetes.
Treatment with continuous subcutaneous insulin infusion (CSII) allows a large degree of treatment individualization and intensification in children with diabetes. The study's aim was to evaluate the impact of treatment with CSII on glycated haemoglobin level (HbA1c) in children with diabetes and investigate whether introduction of CSII is associated with an increased risk of acute complications of diabetes. Patients treated throughout the recruitment period exclusively with multiple daily injections (MDI) were matched for duration of diabetes and HbA1c level at baseline with patients treated exclusively with CSII in a 1:1 group ratio (n = 223 and 231 for MDI and CSII, respectively). The CSII group showed lower HbA1c after the observation period (7.98 ± 1.38 vs. 7.56 ± 0.97; P = 0.002). HbA1c variability measured as standard deviations of average values was also lower in the CSII group (0.73 ± 0.45 vs. 0.84 ± 0.54; P = 0.049). The rate of hospitalization due to acute events was similar in both groups (14.7/100 vs. 14.0/100 person/years in the MDI and CSII group, P = 0.72). Duration of hospital stay per year was on average 1.25 days shorter in the CSII group (P = 0.0004), but the risk of acute complications resulting in hospitalization did not differ between the groups (hazard ratio (HR) 1.16; 95% confidence interval (95% CI) 0.68-1.63). The most significant risk factor for hospitalization due to acute complications was baseline HbA1c concentration (HR 1.25; 95% CI 1.14-1.37). In conclusion, CSII treatment may improve glycemic control and reduce its variability. Change of MDI to CSII does not alter the risk of hospitalization and may reduce the annual duration of hospitalization in children with diabetes.


Gastroesophageal junction of Anatolian shepherd dog; a study by topographic anatomy, scanning electron and light microscopy.
The aim of this study was to cast a spotlight on the topography and to point out the clinical importance of the gastroesophageal junction (GEJ) in Anatolian Shepherd dogs. Nine Anatolian Shepherd dogs were used to study the morphology of the GEJ. The esophagus was appeared has a portion within the thoracic cavity while no portion of the esophagus presented within the abdominal cavity that documented the absence of the intra-abdominal portion in all studied dogs. The topographic anatomy, scanning electron and light microscopic examinations revealed that the gastroesophageal junction was located at the level of the phrenico-esophageal ligament (PEL) inside the esophageal hiatus. Our results were distinguished the morphology of the esophageal and gastric cardiac mucosa at the level of the gastroesophageal junction by the scanning electron micrographs. The light microscopical examination was explained the PEL attached to the esophageal side in one dog and to the gastric cardiac side in three dogs.


The association among diet, dietary fiber, and bowel preparation at colonoscopy.
Pre-colonoscopy dietary restrictions vary widely and lack evidence-based guidance. We investigated whether fiber and various other foods/macronutrients consumed during the 3 days before colonoscopy are associated with bowel preparation quality. This was a prospective observational study among patients scheduled for outpatient colonoscopy. Patients received instructions including split-dose polyethylene glycol, avoidance of vegetables/beans 2 days before colonoscopy, and a clear liquid diet the day before colonoscopy. Two 24-hour dietary recall interviews and 1 patient-recorded food log measured dietary intake on the 3 days before colonoscopy. The Nutrition Data System for Research was used to estimate dietary exposures. Our primary outcome was the quality of bowel preparation measured by the Boston Bowel Preparation Scale (BBPS). We enrolled 201 patients from November 2015 to September 2016 with complete data for 168. The mean age was 59 years (standard deviation, 7 years), and 90% of colonoscopies were conducted for screening/surveillance. Only 17% and 77% of patients complied with diet restrictions 2 and 1 day(s) before colonoscopy, respectively. We found no association between foods consumed 2 and 3 days before colonoscopy and BBPS scores. However, BPPS was positively associated with intake of gelatin, and inversely associated with intake of red meat, poultry, and vegetables on the day before colonoscopy. Our findings support recent guidelines encouraging unrestricted diets >1 day before colonoscopy if using a split-dose bowel regimen. Furthermore, we found no evidence to restrict dietary fiber 1 day before colonoscopy. We also found evidence to promote consumption of gelatin and avoidance of red meat, poultry, and vegetables 1 day before colonoscopy.


Rice straw-derived lipid production by HMF/furfural-tolerant oleaginous yeast generated by adaptive laboratory evolution.
Research on producing medium- and long-chain hydrocarbons as drop-in biofuels has recently accelerated. In addition, lipids are emerging as precursors for biofuel production, and thus, microbial lipid production utilizing agrowastes is becoming a feasible platform technology. Nonetheless, microorganisms are often inhibited by furan aldehydes in biomass-derived hydrolysates. Accordingly, this study aimed to develop oleaginous yeast strains that can tolerate furan aldehydes for producing lipids as biofuel precursors. Rhodosporidium toruloides was selected as the target for adaptive laboratory evolution. The evolved strain, which was obtained from 16 rounds of subcultures, showed a 2.5-fold higher specific growth rate than the wild-type strain in the presence of furan aldehydes and slightly higher lipid production in rice straw hydrolysate. The results discussed in this study provide insights into the production of lipid production by oleaginous yeast utilizing agrowastes as feedstock to obtain drop-in biofuels and contribute to feasible strategies to address climate crises.


Long-Term Quality of Life Following Transthoracic and Transhiatal Esophagectomy for Esophageal Cancer.
The impact of transthoracic (TTE) and transhiatal esophagectomy (THE) on long-term health-related quality of life (HR-QoL) in patients with distal esophageal or gastro-esophageal junction (GEJ) cancer has been studied with variable results. This study investigates long-term HR-QoL in patients having undergone TTE or THE. Disease-free patients after TTE or THE for distal esophageal or GEJ cancer with a follow-up > 2 years were included. Patients who visited the outpatient clinic of a tertiary referral center between 2014 and 2018 were asked to complete EORTC-QLQ-C30 and EORTC-QLQ-OG25 questionnaires. Uni- and multivariable linear regression analysis of HR-QoL was performed in all patients and in subgroups of minimally invasive esophagectomy and neoadjuvant therapy. A total of 132 patients after TTE and 56 after THE were included. When compared with the general population, all patients reported worse HR-QoL in 'role functioning' and 'social functioning' and in a range of disease- and/or treatment-specific symptoms. The only significant difference between TTE and THE was a better HR-QoL score for "hair loss" following TTE (ß = 29.4,95%CI = -49.108 - -9.671, p = 0.016). Subgroup analysis of minimally invasively operated patients showed better scores in "physical functioning" following TTE (ß = 13.8,95%CI = 2.755-24.933, p = 0.030). No significant differences in HR-QoL were found between TTE and THE after neoadjuvant therapy. Long-term HR-QoL is largely comparable in disease-free patients following TTE or THE for distal esophageal or GEJ cancer. If there were differences between the surgical groups, they were in favor of TTE. These findings may aid in preoperative counseling of patients with esophageal or GEJ cancer.


Medical home and pediatric primary care utilization among children with special health care needs.
The medical home model seeks to improve health care delivery by enhancing primary care. This study examined the relationship between the presence of a medical home and pediatric primary care office visits by children with special health care needs (CSHCN) using the data from 2005-2006 National Survey of Children with Special Healthcare Needs. Survey logistic regression was used to analyze the relationship. When CSHCN age, gender, ethnicity/race, functional status, insurance status, household education, residence, and income were included in the model, CSHCN with a medical home were 1.6 times more likely to have six or more annual pediatric primary care office visits than were children without a medical home [odds ratio = 1.60, 95% confidence interval = (1.47, 1.75)]. Female CSHCN, younger CSHCN, children with public health insurance, children with severe functional limitations, and CSHCN living in rural areas also were more likely to have a larger number of visits. By controlling for child sociodemographic characteristics, this study provides empirical evidence about how medical home availability affects primary care utilization by CSHCN.


Synovial fluid kinetics of non-steroidal anti-inflammatory drugs.
Synovial fluid kinetics of NSAIDs are still in a relatively nascent stage. These kinetics are determined by the biochemical characteristics of the drugs, the characteristics of the synovium, and the characteristics of the host. NSAIDs show a delayed peak concentration (relative to serum) in the synovial fluid, and their terminal synovial half-lifes generally parallel the serum half-life. Their intrasynovial concentrations are determined to a large extent by synovial fluid protein concentrations plus diffusional barriers to ingress and egress, although displacing substances (including other drugs), and disease, may complicate kinetics. The synovial pharmacodynamic of NSAIDs are understood very poorly. Hopefully a better understanding of synovial fluid and tissue kinetics will lead to more rational therapy with NSAIDs in the future.


Genitourinary complications in renal transplantation.
The surgical aspects of renal transplantation have now been studied thoroughly. Yet, technical complications are still common. This review may seem too complex, but proper attention to many small details means the difference between success and failure, or at least between large and small morbidity. Reduction of genitourinary complications is due to many innovations. The external ureteroneocystostomy is a primary method of urinary reconstruction which is simpler and produces fewer complications than the alternative procedures. Further, the complications that do occur are more easily and promptly treated. The end-to-side ureteroureterostomy, as currently performed, provides a ready secondary method of reconstruction if the primary method fails. The early exploration and operative correction of genitourinary complications substantially reduces long-term morbidity and mortality.


Tissue and cell-specific antigens in chromatin from cultured rat Sertoli cells.
Cell-specific chromatin antigens have been detected in rat Sertoli cells. Antisera were raised in rabbits to dehistonized chromatin prepared from 5- to 6-day cultures of rat Sertoli cells and immunoreactivity was assessed with microcomplement fixation tests or immunoidentification of antigens separated electrophoretically and transferred to nitrocellulose sheets. Tissue specificity was confirmed further by immunoabsorption. These antisera recognized only components of Sertoli cell chromatin; chromatins prepared from rat liver, kidney, thymus, Novikoff hepatoma, a testes germinal cell fraction, or purified rat DNA showed little or no immunoreactivity. Nitrocellulose transfers of total chromosomal proteins revealed the presence of two high-molecular-weight antigens (greater than 200,000) and a broad range of weaker immunologic species (M tau about 50,000-200,000) in Sertoli cell chromatin but not liver or thymus chromatin. Deproteinization of Sertoli cell chromatin with concentrated salt and urea at pH 6 or 8 produced an increase in complement-fixing activity of the fraction sedimenting with DNA and micrococcal nuclease digestion studies showed these fractions to depend in part on DNA for antigenicity. Individual antigens in the protein-DNA pellets of pH 8 salt and urea fractionated chromatin could not be identified with antigens on nitrocellulose sheets. Collectively, these observations suggest that at least two groups of cell-specific antigens exist in Sertoli cell chromatin; one group is detected after electrophoretic separation and transfer to nitrocellulose and the other group, reactive in complement fixation, cannot be detected through this method, apparently becoming antigenically inactive once the complex of protein and DNA is dissociated.


Risk factors for malaria: a microepidemiological study in a village in Sri Lanka.
Environmental and socioeconomic risk factors for malaria were studied in a village in Sri Lanka. Over a period of one year, all 49 households in the village were visited every alternate day to obtain information on malaria episodes. Information on risk factors was obtained through questionnaires and direct observations. Age below 17 years (relative risk [RR] = 1.66, 95% confidence interval [95% CI] 1.18-2.35), use of bed nets (RR = 0.16, 95% CI 0.05-0.45) and traditional fumigants (RR = 0.58, 95% CI 0.37-0.93) were independent predictors of malaria. People using anti-mosquito pyrethrum coils had a higher risk for malaria than people living in houses where they were not used (RR = 1.46, 95% CI 1.03-2.07). The build-up of Anopheles culicifacies populations before the start of the transmission season had taken place in a stream near the village. Living close to the stream was a risk factor for malaria early in the transmission season, although this did not reach statistical significance (comparing < 250 m with > 500 m, RR = 2.13, 95% CI 0.96-4.71).


Balloon assessment of patent foramen ovale morphology and the modification of tunnels using a balloon detunnelisation technique.
(1) To define patent foramen ovale (PFO) morphology using balloon assessment and identify those with long tunnel type morphology. (2) To describe a novel technique of detunnelisation to facilitate PFO device closure in patients with long tunnel PFO morphology. An appreciation that PFO morphology varies from simple defects through to long tunnel-like defects is important for their successful transcatheter closure. Using standard closure techniques for long tunnels can be problematic. Consecutive patients who underwent transcatheter PFO closure from April 1, 2005 to March 31, 2006 had assessment of PFO morphology using a compliant sizing balloon. The sites of constraint of the balloon allowed identification of the PFO entrance, exit, and length. The PFO was classified as being a long tunnel when the length was greater than the diameter of either the entrance or exit. Those with a long tunnel had detunnelisation performed and the defect was then closed. 44 patients (32 females), mean age 50 years were studied. On balloon assessment 10 (23%) met the criteria for long tunnels. Detunnelisation allowed successful closure with the STARFlex (NMT Medical, Boston, MA) device in 9 of 10 patients. In the other case transseptal puncture was required after detunnelisation before closure. Balloon assessment of PFOs enhances the understanding of their morphology and aids the identification of long tunnels. Detunnelisation using the same balloon facilitates the uncomplicated transcatheter closure of long tunnel PFOs in most patients.


Asthma mortality attributable to ambient temperatures: A case-crossover study in China.
Whether ambient temperature exposure contributes to death from asthma remains unknown to date. We therefore conducted a case-crossover study in China to quantitatively evaluate the association and burden of ambient temperature exposure on asthma mortality. Using data from the National Mortality Surveillance System in China, we conducted a time-stratified case-crossover study of 15 888 individuals who lived in Hubei and Jiangsu province, China and died from asthma as the underlying cause in 2015-2019. Individual-level exposures to air temperature and apparent temperature on the date of death and 21 days prior were assessed based on each subject's residential address. Distributed lag nonlinear models based on conditional logistic regression were used to quantify exposure-response associations and calculate fraction and number of deaths attributable to non-optimum ambient temperatures. We observed a reverse J-shaped association between air temperature and risk of asthma mortality, with a minimum mortality temperature of 21.3 °C. Non-optimum ambient temperature is responsible for substantial excess mortality from asthma. In total, 26.3% of asthma mortality were attributable to non-optimum temperatures, with moderate cold, moderate hot, extreme cold and extreme hot responsible for 21.7%, 2.4%, 2.1% and 0.9% of asthma mortality, respectively. The total attributable fraction and number was significantly higher among adults aged less than 80 years in hot temperature. Exposure to non-optimum ambient temperature, especially moderate cold temperature, was responsible for substantial excess mortality from asthma. These findings have important implications for planning of public-health interventions to minimize the adverse respiratory damage from non-optimum ambient temperature.


Treatment of multiple myeloma with deoxycoformycin.
A comparison of adenosine deaminase activity in intact human plasma cells and lymphocytes in vitro showed that plasma cells had at least as much activity of this enzyme as did T or non-T lymphocytes. This observation led us to examine the effectiveness of deoxycoformycin in the treatment of multiple myeloma. Thirteen patients with advanced refractory myeloma were treated with deoxycoformycin at 5 mg/m2 daily for 3 days every 2 weeks until response or progression. Of the seven evaluable patients who received more than one cycle of therapy, two had a greater than 50% reduction in the level of myeloma protein and two had a demonstrable reduction in soft tissue disease. Toxicity consisted of marked nausea, anorexia lasting several days, and mild transient confusion in some patients. Plasma levels of deoxyadenosine and adenosine peaked on day 4 or 5 with average values of 1.9 and 0.6 microM, respectively. Red cell levels of dATP reached approximately 40% of ATP levels. The viability of plasma cells was shown to be greatly reduced in in vitro incubations with deoxycoformycin and low levels of deoxyadenosine (ID50 of 6 microM).


Halodule pinifolia (Seagrass) attenuated lipopolysaccharide-, carrageenan-, and crystal-induced secretion of pro-inflammatory cytokines: mechanism and chemistry.
The study aimed to explore the anti-inflammatory effect, underlying mechanism, and chemistry of Halodule pinifolia extract. The ethyl acetate (EHP) and methanol (MHP) extracts of Halodule pinifolia were screened for pro-inflammatory cytokine inhibition effect under various in vitro (LPSand crystal-induced inflammation) and in vivo models (LPS-induced endotoxaemia model, carrageenan-induced paw oedema model, and oxalate-induced renal nephropathy model of inflammation). The effect of EHP on the expression of inflammatory markers using western blot analysis (in vitro) was investigated. Chemical constituents of bioactive EHP were isolated through chromatography and characterised using NMR spectroscopy. Furthermore, EHP was standardised for rosmarinic acid, vanillic acid, and ethyl protocatechuate using HPLC. Also, total phytosterols, phenolic, and flavonoid content of EHP were determined by UV spectroscopy. EHP was comparatively more effective than MHP in inhibiting cytokines secretions under LPS-induced in vitro models. Furthermore, EHP was screened under endotoxaemia in vivo model, EHP (250 mg/kg) reduced plasma IL-6, TNF-α, and IL-1β levels by 88.3%, 78.2%, and 74.5%, respectively. In the carrageenan-induced oedema model, EHP (200 mg/kg) reduced paw volume and release of TNF-α (69.3%) and IL-1β (43.1%). EHP (200 mg/kg) further controlled renal nephropathy by inhibiting plasma IL-1β and BUN levels. Also, a significant reduction of mRNA expressions of TNF-α and IL-1β and KIM-1 in renal tissues was observed. Through western blot, EHP was identified to regulate the expression of pro-form as well as mature-form of IL-1β and caspase-1. EHP constituted rosmarinic acid (RA), vanillic acid (VA), ethyl protocatechuate (EP), sitosterol, stigmasterol, campesterol, and dihydrobrassicasterol. It was determined that 4.6 mg/g of RA, 2.92 mg/g of VA, 0.76 mg/g of EP, 21.7 mg/g of total phenolics, 29.8 mg/g of total flavonoids, and 48.2 mg/g of total phytosterols were present in dry EHP. The presence of anti-inflammatory constituents such as RA, VA, and PE in EHP corroborated the in vitro and in vivo anti-inflammatory activity of EHP. The anti-inflammatory property of EHP and its action through attenuation of pan-cytokines suggest that it can be developed into an oral pharmaceutical drug.


Successful management of pacing system malfunctions without surgery: the role of programmable pulse generators.
The value of programmable pulse generators for correcting pacing system malfunction without surgical revision was assessed in 293 patients. Twenty-five patients (8.5%) developed malfunctions from one day to 38 months after implant. Of these, 16 or 64% were successfully managed by programming alone, while nine patients required lead repositioning or a new lead. The majority (75%) of isolated pacing and sensing malfunctions were corrected by programming, but programming restored normal pacing function in only one of five patients who had combined sensing and pacing malfunctions which appeared early after pacemaker insertion. We conclude that programmable pulse generators are particularly useful for managing isolated pacing or sensing malfunctions. However, programmability is not a substitute for careful lead placement.


Role of intravenous cloxacillin for inpatient infections.
One of the issues of antibiotic treatment is to warrant its optimal effectiveness while minimizing the risk for emergence of resistance. The time above minimal inhibiting concentration (MIC) (T>MIC) is the best predictive pharmacological parameter of effectiveness for antibiotics with time-dependent activity, such as cloxacillin. Cloxacillin is the first line antibiotic in a great number of clinical situations generated by methicillin sensitive staphylococci, because of its intrinsic properties: bactericidal effect, tissue distribution and safety. The most recent anti-staphylococcal agents do not improve treatment of MSSA infections compared to penicillin M and especially cloxacillin. Cloxacillin has a narrow microbiological spectrum. This ecological feature is in line with the recommendation to use antibiotics with the narrowest spectrum to reduce the pressure of selection. The consensus is to have T>MIC for at least 40% of the dosing interval and is achieved by infusing 2g of cloxacillin per day (T>MIC=50%) or four infusions of 3g per day (T>MIC=42%) in adults.


Franklin, Lavoisier, and Mesmer: origin of the controlled clinical trial.
In 1784, a Royal Commission headed by Benjamin Franklin and Antoine Lavoisier designed a series of ingenious experiments to debunk France's greatest medical rogue, Anton Mesmer, and his bizarre healing of illnesses based on his bogus theory of animal magnetism. Using intentional subject ignorance and sham interventions to investigate mesmerism, Franklin's commission provided a model for the controlled clinical trial.


A differential detailed diffusion-weighted imaging-ASPECTS for cerebral infarct volume measurement and outcome prediction.
Diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) has been used to estimate infarct core volume in acute stroke. However, the same and indiscriminate score deduction for punctate or confluent DWI high-intensity lesion might lead to variation in performance. To develop and evaluate a differential detailed DWI-ASPECTS method in comparison with the conventional DWI-ASPECTS in core infarct volume measurement and clinical outcome prediction. We retrospectively recruited patients with acute ischemic stroke (AIS) treated with endovascular treatment between April 2013 and October 2019. In differential detailed DWI-ASPECTS, restricted diffusion lesion that was punctate or less than half of a cortical region (M1-M6) would not lead to subtraction of point. A favorable outcome was modified Rankin Scale score ⩽2 at 90 days after stroke onset. Among 298 AIS patients, mean age was 75 years (interquartile range (IQR) 67-82), and 194 patients (65%) were males. Mean infarct core volume was 11 mL (IQR 3-37). Overall, the score by detailed DWI-ASPECTS was significantly higher than conventional DWI-ASPECTS (8 (7-9) vs. 7 (5-9); P < 0.01). The detailed DWI-ASPECTS resulted in a higher correlation coefficient (r) for core infarct volume estimation than the conventional DWI-ASPECTS (r = 0.832 vs. 0.773; P < 0.01). Upon re-classification of those scored ⩽6 in conventional DWI-ASPECTS (n = 134) by detailed DWI-ASPECTS, the rate of favorable outcome in patients with detailed DWI-ASPECTS >6 was significantly higher than those with ⩽6 (29 (48%) vs. 14 (19%); P < 0.01). Detailed DWI-ASPECTS appeared to provide a more accurate infarct core volume measurement and clinical outcome correlation than conventional DWI-ASPECTS among AIS patients treated with endovascular therapy.


PD 141955 and CI-972: 9-deazaguanine analog purine nucleoside phosphorylase inhibitors. I. Suppression of the human mixed lymphocyte reaction (MLR).
Inhibitors of purine nucleoside phosphorylase (PNP) are of interest as potential T-cell-selective immunosuppressive agents and for other uses. PD 141955 (9-deaza-9-(3-thienylmethyl)guanine; 2-amino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d]pyrimidin -4-one) is 12- to 100-fold more potent than CI-972 (8-amino-9-deaza-9-(3-thienylmethyl)guanine; 2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d]pyrim idin-4- one) in PNP enzyme inhibition assays. In the human MLR, PD 141955 has IC50s of 2.8 and 12.8 microM in the presence and absence, respectively, of 15 microM GdR (means from 10 assays), while the IC50s of CI-972 tested in parallel are > 30 microM. Concentration-dependent accumulation of dGTP occurs in PD 141955-treated MLRs under conditions in which CI-972 lacks detectable activity. Thus, consistent with its greater PNP inhibitory activity in a cell free system, PD 141955 is significantly more potent than CI-972 in its ability to suppress the MLR.


Heart valve calcification in young patients with systemic lupus erythematosus: a window to premature atherosclerotic vascular morbidity and a risk factor for all-cause mortality.
The objective of the study was to evaluate the association between heart valve calcification and atherosclerosis and outcome in systemic lupus erythematosus (SLE). One-hundred and seven patients with SLE (mean age 45.9 +/- 14.7 years) were studied by 2D transthoracic echocardiography. Mitral annulus calcification (MAC) was detected in 24 patients (22.6%) and aortic valve calcification (AVC) in 22 (20.1%). Both MAC and AVC were associated with older age (r = 0.2, p = 0.02; r = 0.40, p <or= 0.001, respectively), high SLE damage index (r = 0.3, p = 0.005; r = 0.40, p = 0.001, respectively), diabetes mellitus (r = 0.2, p = 0.05; r = 0.3, p = 0.003, respectively), hyperlipidemia (r = 0.03, p = 0.01; r = 0.03, p = 0.001, respectively), hypertension (r = 0.20, p = 0.07; r = 0.20, p = 0.08, respectively), serum IgA isotype of anticardiolipin antibody (r = 0.03, p = 0.03; r = 0.04, p = 0.02, respectively), increased serum creatinine (r = 0.03, p = 0.0005; r = 0.12, p = 0.02, respectively), and stroke (r = 0.3, p = 0.0008; r = 0.35, p = 0.0002, respectively). In addition, MAC was associated with coronary artery disease (r = 0.2, p = 0.05). Both MAC and AVC were significantly associated with death during the follow-up period (n = 9, 8.6%) (r = 0.20, p = 0.05; r = 0.20, p = 0.03, respectively). On stepwise logistic regression analysis, MAC and AVC are independently associated with hyperlipidemia and antiphospholipid antibodies. In conclusion, MAC and AVC are prevalent among young SLE patients, positively correlate with premature diffuse atherosclerosis, and are a risk factor for subsequent all-cause mortality.


[Addictions and psoriasis: an example of the dermatologist's implication in preventive medicine ?].
Association between psoriasis and addictive disorders has been longtime suspected and several studies are supporting the association of psoriasis and alcohol, and of psoriasis and tobacco. The association of psoriasis and other addictive disorders has not yet been reported. The association of psoriasis and alcohol is not restricted to alcoholism (defined as excessive alcohol consumption with psychic and/or psychic (correction of physic) dependence). It has been suggested that psoriasis is more closely linked to alcohol misuse than it is to alcoholism. The association of psoriasis and alcohol seems not been influenced by the gender, and shows a dose-effect relation. The most striking link between cigarette smoking and psoriasis has been established in palmo-plantar pustulosis. This link also seems to exist for other forms of psoriasis, with a dose-effect relation. Cigarette smoking could be involved in the high prevalence of lung cancer and cardio vascular disorders in psoriatic patients. There are a number of difficulties in the assessment of the correlation between psoriasis, cigarette smoking, and alcohol, and even more so in establishing a causal or etiologic relationship between the three, because of several confusion factors. This must not occult the reality of this association and its impact of psoriatic patients' health and the importance of detecting and preventing them. The detection and the prevention of the complications of these addictions belong to the dermatologists.


Nutritional Status, Body Composition, and Bone Health in Women After Bariatric Surgery at a University Hospital in Rio de Janeiro.
Calcium and/or vitamin D deficiency can occur after Roux-en-Y gastric bypass (RYGBP) because of impaired absorption, resulting in secondary hyperparathyroidism and increased risk of reduced bone mineral density (BMD). The objective of this study is to assess nutritional status, body composition, and bone health in women after RYGBP. Twenty-five premenopausal women who had undergone RYGBP (test group) and 33 women matched for age and body mass index who had not undergone surgery (control group) participated. Test group received 250 mg of calcium for day. Anthropometric, dietary, laboratory, body composition, and BMD (X-ray absorptiometry) analyses were performed. No differences were found between the groups in waist circumference, fat or lean mass, BMD, or dietary calcium intake, although calcium intake was low in both groups. The test group had better results for complete blood count, total cholesterol, low-density lipoprotein, and triglycerides. The mean parathyroid hormone was higher (p = 0.005) in the test group, although still within normal limits. Plasma levels of 25-hydroxyvitamin D were low in groups but did not differ between them (p = 0.075). Vitamin D concentrations were lower in women with longer time since surgery. The test group had lower intake of energy, protein, lipids, polyunsaturated fatty acids, fiber, phosphorus, and iron than the control group. Elevation of parathyroid hormone, low dietary calcium intake, and vitamin D plasma insufficiency without BMD reduction occurred after RYGBP. Patients who underwent RYGBP had adequate lipid profiles but inadequate intake protein, polyunsaturated fatty acids, fiber, and iron. Vitamin D deficiency may occur in the late postoperative period.


Myoelectric changes in the triceps surae muscles under sustained contractions. Evidence for synergism.
Synergistic behaviour of triceps surae muscles (medial gastrocnemius-MG, lateral gastrocnemius-LG, soleus-SOL) during sustained submaximal plantarflexions was investigated in this study. Six male subjects were asked to sustain an isometric plantar flexor effort to exhaustion at two different knee angles. Exhaustion was defined as the point when they could no longer maintain the required tension. The loads sustained at 0 and 120 degrees of knee flexion represented 50% and 36% of their maximum voluntary contraction (MVC) respectively. MVC was measured at 0 degree knee flexion. During the contractions, electromyograms (EMG) from the surface of the triceps surae muscles were recorded. Changes in the synergistic behaviour of the triceps surae were assessed via partial correlations of the average EMG (AEMG) between three muscle combinations; MG/LG, MG/SOL, LG/SOL, and correlation between SOL/MG + LG and MG/SOL + LG. The latter combinations were based on either common fibre type or innervation properties. Two types of synergisms were identified: trade-off and coactivation. Trade-off and coactivation synergies were defined by significant (p less than 0.05) positive and negative correlations respectively. Coactivation synergism was found to occur predominantly under conditions of high load or reduced length of the triceps surae, and increased with the duration of the contraction. Trade-off synergism was evident when the muscles were at their optimum length and the loads sustained were submaximum.(ABSTRACT TRUNCATED AT 250 WORDS)


Thymus-dependent increase in number of T cells in parathymic lymph nodes induced by the biscoclaurine alkaloid, cepharanthine.
In mice treated with cepharanthine (Cepha), a biscoclaurine alkaloid, the number of T cells was increased in the parathymic lymph nodes (PtLNs) which are considered to be the specialized lymph nodes in local differentiation of T cells. Such PtLN cells exhibited augmented proliferative responses to T cell mitogens and exogenous interleukin 2 (IL 2) and showed a great ability to produce IL2, which suggests an increase in mature T cells in the PtLN. However, such increases in the number of T cells and in the mitogen response were not observed in adult thymectomized mice. A low level of plasma prostaglandin E2 (PGE2) was observed in Cepha-treated mice. Replenishment of the PGE2 in such mice with exogenous PGE2 prevented the increase in T cells in the PtLN. These results suggest that the migration of mature T cells from the thymus to PtLN is increased by Cepha and that Cepha is able to regulate their traffic by a prostaglandin-mediated system.


Specific control of follicle stimulating hormone in the male: postulated site of action of inhibin.
Serum luteinizing and follicle stimulating hormone concentrations were related to gonadal function, as reflected by sperm count and serum testosterone concentrations, in a group of men studied over 10 years after surgical correction of bilateral cryptorchidism in childhood. The results indicated that while all degrees of gonadal function occurred in these patients, the main adverse effect of cryptorchidism was on spermatogenesis. In some of the patients with oligospermia and normal Leydig cell function there was an isolated increase of basal serum FSH concentrations, suggesting a specific impairment of the testicular production of 'inhibin'. Gonadotrophin releasing hormone (LHRH) tests in these patients were compared to those in patients with normal basal gonadotrophins and to those with elevated basal LH and FSH concentrations. A selective exaggeration of the FSH response to exogenous LHRH in the group of patients with a monotropic elevation of FSH concentrations suggests that 'inhibin' modulates the secretion of FSH by an action on the pituitary rather than by modifying endogenous LHRH production by the hypothalamus.


Taurine receptor: kinetic analysis and pharmacological studies.
A new procedure for the preparation of the taurine receptor from mammalian brain is described. The taurine receptor thus prepared shows a Kd of 92 nM, Bmax of 6.0 pmol/mg protein and Hill coefficient of 0.90 suggesting a single site model for the binding of 3H-taurine to the receptor. The binding of 3H-taurine to the receptor is highly specific and is not affected by agonists and antagonists of other receptors such as glutamate, quisqualic acid, kainate and NMDA for the glutamate receptor; glycine and strychnine for the glycine receptor; FNZP for the benzodiazepine receptor; picrotoxin and bicuculline for the GABAB receptor. However, analogues of taurine (e.g., homotaurine and hypotaurine) are potent inhibitors inhibiting more than 50% of 3H-taurine binding at 0.1 microM. Taurine receptor binding is not significantly affected by monovalent cations (e.g., Na+, K+, Li+ and NH4+) at 1 mM or divalent cations (e.g., Mg2+, Ca2+, Ba2+ and Mn2+) at 0.1 mM. However, the binding was completely abolished by Co2+, Zn2+ and Hg2+ at 0.1 mM, suggesting the presence of free sulfhydryl groups near or at the ligand binding site. Among the amino acids tested, cysteic acid was the most potent inhibitor, followed by beta-alanine, valine, tyrosine and cysteine inhibiting 3H-taurine to an extent of 84, 66, 63, 62, and 58% of 1 mM, respectively. Nucleotides and second messengers (e.g., ATP, ADP, cAMP, GTP, cGMP and diacyl glycerol) do not inhibit 3H-taurine binding significantly at 0.1 mM. From above studies, it seems that the taurine receptor is not up- or down-regulated by ions or second messengers at the taurine binding site. Whether the taurine receptor is coupled to a G-protein mediated second messenger system is currently under investigation.


Corrigendum: Decreased Risk of Anxiety in Diabetic Patients Receiving Glucagon-Like Peptide-1 Receptor Agonist: A Nationwide, Population-Based Cohort Study.
[This corrects the article DOI: 10.3389/fphar.2022.765446.].


[Study of the equilibrium conditions for the extractive purification of oleandomycin].
Dependence of the oleandomycin distribution coefficient on the antibiotic concentration, duration of the filtrate storage, extraction temperature and salting-out agents was studied. The distribution coefficient of oleandomycin in the system of fermentation broth filtrate--butylacetate was much lower (about 3 times) than that in the system of oleandomycin phosphate aqueous solution--butylacetate. Addition of sodium sulfate to the aqueous phase provided a significant increase in the oleandomycin distribution coefficient.


Effect of different restorative crown design and materials on stress distribution in endodontically treated molars: a finite element analysis study.
The purposes of this simulation study were to evaluate the stresses in the roots of endodontically treated molars with extensive coronal tissue loss which were restored by endocrowns (all-in-one core and crown) and traditional crowns with post-cores, during masticatory simulation using finite element analysis. A mesio-distal cross-section of a lower right first molar was digitized and used to create 2-dimensional models of the teeth and supporting tissue; different crown designs, viz., endocrown with 2 mm occlusal clearance, endocrown with 4 mm occlusal clearance and post-core crown; different crown materials, viz., zirconia (Zr) and lithia-disilicate reinforced glass ceramic (LDRGC), and different post and core materials, viz., glass fiber (GF), stainless steel (SS) and metal cast (MC). An axial load of 600 N was applied to the central fossa of occlusal surface. The stress distributions were similar between Zr and LDRGC for periodontal ligament and alveolar bone. The root canal inner wall maximum principal stresses of SS post (70.8 MPa) and MC post (71.4 MPa) were higher than that of GF post (36.0 MPa) and endocrown (2.4 MPa). The endocrowns reduced stress concentration for the root canal inner wall in comparison with the conventional post-core crown. Molars restored with endocrowns are less prone to root fracture than those with posts.


CT fluoroscopy-guided percutaneous vertebroplasty for the treatment of osteolytic breast cancer metastases: results in 62 sessions with 86 vertebrae treated.
This retrospective study aimed to assess the results of computed tomographic (CT) fluoroscopy-guided percutaneous vertebroplasty (PV) of painful osteolytic spinal metastases from breast cancer, focusing on the frequency and clinical impact of polymethylmethacrylate (PMMA) leaks. Within 48 months, 53 patients (52 women; mean age of 62 y +/- 13) with painful osteolytic breast cancer metastases underwent vertebroplasty. Eighty-six vertebrae were treated in 62 sessions under CT fluoroscopy guidance (single slice and four- and 16-row CT). In the planning CT scan, osteolytic destruction (ie, none, < or =25%, < or =50%, < or =75%, or < or =100%) was assessed regarding the vertebral cross-sectional area, the cortical border of the spinal canal, and the outer circumference. CT performed after vertebroplasty was used to detect local PMMA leaks (intradiscal, intraspinal, paravertebral, intercostovertebral/posterolateral, and vascular). Patient charts were reviewed with respect to adverse events. Clinical outcome was assessed on a visual analog scale (VAS) 24 hours before, immediately after, and 6 months after PV. Overall, 37.2%, 12.8%, and 1.2% of vertebrae (N = 86) showed at least a 50% osteolytic involvement of the cross-sectional area, spinal canal, and outer vertebral cortex, respectively. Intradiscal, intraspinal, paravertebral, and intercostovertebral/posterolateral leaks were seen in 31.3%, 26.9%, 26.9%, and 14.9% of vertebrae, respectively. The ratio of basivertebral to segmental venous leaks was 22.4%/23.9%. No major complications (eg, radiculopathy or pulmonary embolism) occurred. VAS scores decreased significantly (P < .05) from 6.4 at 24 hours before PV to 3.4 at a mean follow-up of 9.2 months. PV of osteolytic breast cancer metastases can be performed safely under CT fluoroscopic guidance even with substantial involvement of the vertebral cross-sectional area or cortical bone. A high clinical success rate was achieved and cortical and vascular PMMA leaks had no impact.


Day care and early childhood settings. Fostering mental health in young children.
The authors, with research supporting the relationship between experience and the developing brain, envision a new and innovative model of child care in which principles of child development and mental health play an integral role. The School of the Twenty-first Century, although housed in existing school buildings, will be far more than a traditional 8:00 AM-to-3:00 PM educational facility. It will become a hub of child and family life in the community and provide institutional and outreach services for children from birth to 12 years of age. Active developmental and mental health programs that provide education for parents, primary caretakers, and other providers are central to the model. These programs will include preventive, evaluative, and treatment services for children. The child psychiatrist is viewed as an important member of the mental health team, who helps identify, assess, and treat children with developmental and psychiatric difficulties.


MHC class II gene silencing in trophoblast cells is caused by inhibition of CIITA expression.
Major histocompatibility complex (MHC) class II molecule expression is specifically suppressed on fetal trophoblasts, even in response to interferon (IFN)-gamma, a potent inducer of MHC class II genes. The suppression of class II induction has been suggested to play a role in preventing rejection of the fetal allograft. The mechanism of this suppression is unknown. Human trophoblast cell lines were examined for expression of MHC class II transcription factors and for activity of the IFN-gamma signaling pathway. Additionally, trophoblast cells were transfected with a vector expressing the class II transactivator, CIITA, and assayed for class II expression. The MHC class II transcription factors RFX and X2BP and the IFN-gamma signaling pathway components are expressed constitutively and are functional in trophoblasts. However, CIITA expression was absent in trophoblasts and could not be induced by IFN-gamma. Transfection of CIITA into trophoblast cells resulted in derepression of class II gene expression. The lack of induction of MHC class II genes in response to IFN-gamma in trophoblast cells is caused neither by the absence of factors that bind class II promoters, nor by a lesion in the IFN-gamma signaling pathway, but results from a specific inhibition of the CIITA gene.


Racial differences in estimated GFR decline, ESRD, and mortality in an integrated health system.
Current evidence does not clearly identify the contribution of kidney function decline and mortality to racial disparities in end-stage renal disease (ESRD) incidence. We used observed estimated glomerular filtration rate (eGFR) to project the time of onset of kidney failure and examined mortality to better understand these racial disparities. Retrospective cohort. Adult members of Kaiser Permanente Southern California in 2003-2009 with more than 2 serum creatinine tests and more than 180 days between tests: 526,498 whites, 350,919 Hispanics, 136,923 blacks, and 105,476 Asians. Race/ethnicity. ESRD (dialysis or transplantation); mortality. eGFR decline was modeled using linear regression. Kidney failure was projected based on predicted eGFR <15 mL/min/1.73 m² at specified times. Racial differences in projected kidney failure and mortality in those with projected kidney failure were estimated with adjustment for age, sex, and entry eGFR. Blacks had more extreme rates of eGFR decline (1st percentile, -23.6 mL/min/1.73 m² per year), followed by Hispanics (-20.9 mL/min/1.73 m² per year), whites (-20.1 mL/min/1.73 m² per year), and Asians (-17.6 mL/min/1.73 m² per year; P < 0.001). There were 25,065 whites, 11,368 Hispanics, 6,785 blacks, and 3,176 Asians with projected kidney failure during the study period. The ORs for projected kidney failure versus whites during CKD stages 3 and 4 were 1.54 (95% CI, 1.46-1.62) in blacks, 1.49 (95% CI, 1.42-1.56) in Hispanics, and 1.41 (95% CI, 1.32-1.51) in Asians. For those with projected kidney failure, the HRs of death versus whites during CKD stages 3 and 4 were 0.82 (95% CI, 0.77-0.88) in blacks, 0.67 (95% CI, 0.63-0.72) in Hispanics, and 0.58 (95% CI, 0.52-0.65) in Asians. Results may not generalize to the uninsured or subgroups within a race. Projected kidney failure was based on linear trends from clinically obtained eGFR. We found more extreme rates of eGFR decline in blacks. Projected kidney failure during CKD stages 3 and 4 was high in blacks, Hispanics, and Asians relative to whites. Mortality for those with projected kidney failure was highest in whites. Differences in eGFR decline and mortality contributed to racial disparities in ESRD incidence.


Biogenic production of silver, zinc oxide, and cuprous oxide nanoparticles, and their impregnation into textiles with antiviral activity against SARS-CoV-2.
Nanotechnology is being used to fight off infections caused by viruses, and one of the most outstanding nanotechnological uses is the design of protective barriers made of textiles functionalized with antimicrobial agents, with the challenge of combating the SARS-CoV-2 virus, the causal agent of COVID-19. This research is framed within two fundamental aspects: the first one is linked to the proposal of new methods of biogenic synthesis of silver, cuprous oxide, and zinc oxide nanoparticles using organic extracts as reducing agents. The second one is the application of nanomaterials in the impregnation (functionalization) of textiles based on methods called "in situ" (within the synthesis), and "post-synthesis" (after the synthesis), with subsequent evaluation of their effectiveness in reducing the viral load of SARS-CoV-2. The results show that stable, monodisperse nanoparticles with defined geometry can be obtained. Likewise, the "in situ" impregnation method emerges as the best way to adhere nanoparticles. The results of viral load reduction show that 'in situ' textiles with Cu2O NP achieved a 99.79% load reduction of the SARS-CoV-2 virus.


Current and future role of circulating tumor cells in patients with epithelial ovarian cancer.
Circulating tumor cells (CTCs) are viable tumor cells that are released into the circulatory system. CTCs have shown a prognostic value in numerous solid tumors. CTC research in epithelial ovarian carcinoma (EOC) has attracted only little attention. Since the primary route of metastasis in EOC is considered to be direct peritoneal spread in the abdominal cavity and distant metastases only occur in one third of the patients, it was thought that there is not enough shedding of tumor cells in the circulation. Nevertheless recent studies revealed an important role of hematogenous spread in EOC and showed that CTC status is associated with advanced tumor stage, CA-125 levels and residual disease after surgery. Furthermore the presence of CTCs correlates with shorter overall and disease free survival. However this prognostic value of CTCs in EOC seems to depend on the used isolation and detection methods. In EOC function- or density based enrichment methods seem to offer more promising results then epithelial cell adhesion molecule (EpCAM)-based approaches. This can be explained by a low number of EpCAM positive CTCs in EOC and the downregulation of EpCAM during epithelial-to-mesenchymal transition (EMT). The presence of CTCs might also have predictive value as CTC status was associated with treatment response in two studies and CTCs showed to be a better monitoring tool then CA-125 in a small population. The (genotypic) characterization of CTCs might become even more important in the future paving the way for CTCs to a true predictive "liquid tumor biopsy".


Prognostic value of depression and anxiety on breast cancer recurrence and mortality: a systematic review and meta-analysis of 282,203 patients.
Depression and anxiety are common comorbidities in breast cancer patients. Whether depression and anxiety are associated with breast cancer progression or mortality is unclear. Herein, based on a systematic literature search, 17 eligible studies involving 282,203 breast cancer patients were included. The results showed that depression was associated with cancer recurrence [1.24 (1.07, 1.43)], all-cause mortality [1.30 (1.23, 1.36)], and cancer-specific mortality [1.29 (1.11, 1.49)]. However, anxiety was associated with recurrence [1.17 (1.02, 1.34)] and all-cause mortality [1.13 (1.07, 1.19)] but not with cancer-specific mortality [1.05 (0.82, 1.35)]. Comorbidity of depression and anxiety is associated with all-cause mortality [1.34 (1.24, 1.45)] and cancer-specific mortality [1.45 (1.11, 1.90)]. Subgroup analyses demonstrated that clinically diagnosed depression and anxiety, being female and of younger age (<60 years), and shorter follow-up duration (≤5 years) were related to a poorer prognosis. Our study highlights the critical role of depression/anxiety as an independent factor in predicting breast cancer recurrence and survival. Further research should focus on a favorable strategy that works best to improve outcomes among breast cancer patients with mental disorders.


Sorsby's fundus dystrophy tissue inhibitor of metalloproteinases-3 (TIMP-3) mutants have unimpaired matrix metalloproteinase inhibitory activities, but affect cell adhesion to the extracellular matrix.
The TIMP family of matrix metalloproteinase inhibitors consists of four members, of which TIMP-1, -2 and -4 are secreted, freely diffusible proteins, whereas TIMP-3 is ECM-associated. Mutations in the TIMP3 gene have been linked to Sorsby's fundus dystrophy (SFD), an autosomal dominant inherited retinal degenerative disease that leads to blindness. The SFD mutations characterized result in introduction of an unpaired cysteine residue in the C-terminal domain of TIMP-3. We have expressed four SFD mutant TIMP-3 proteins in baby hamster kidney (BHK) cells and evaluated their characteristics alongside wild-type TIMP-3. Analysis of the mutant proteins (Ser156Cys, Gly167Cys, Tyr168Cys and Ser181Cys) by SDS-PAGE and reverse zymography revealed that each of the mutants retained gelatinase A and gelatinase B inhibitory activity, and were localized to the ECM. Association rate constants for Ser156Cys TIMP-3 with gelatinase-A, gelatinase-B, stromelysin-1 and collagenase-3 were only moderately reduced compared to wild-type TIMP-3. However, all of the mutants displayed aberrant protein-protein interactions, resulting in the presence of additional proteins or complexes in ECM preparations. Two of the mutants (Ser156Cys and Ser181Cys) showed a marked propensity to form multiple higher molecular-weight complexes that retained TIMP activity on reverse zymography. Expression of the SFD mutant TIMP-3 (and to a lesser extent, wild-type TIMP-3) proteins in BHK cells conferred increased cell adhesiveness to the ECM. Our findings indicate that the pathogenesis of Sorsby's fundus dystrophy cannot be attributed to a failure to localize SFD TIMP-3 proteins to the ECM or defects in MMP inhibition, but may involve the formation of aberrant TIMP-3-containing protein complexes and altered cell adhesion.


Evidence for a glycidic-lipidic matrix in human neuromelanin, potentially responsible for the enhanced iron sequestering ability of substantia nigra.
The high-resolution solid-state 13C-NMR spectrum of a neuromelanin specimen (from patients dying from nonneurological diseases) is compared with that obtained from enzymatically prepared dopamine-melanin. The main differences between the two spectra suggest the occurrence in neuromelanin of a glycidic/lipidic matrix tightly associated with the melanin macromolecule. Atomic emission spectroscopy revealed high iron content (1.5%) in the neuromelanin specimen, in full agreement with previous reports. These observations support the view that neuromelanin acts as a strong chelating (and insolubilizing) system for iron ions and further suggest that the attack to this compact composite substrate may be an important step to allow the release of iron ions responsible for the increased lipid peroxidation reported in the pathogenesis of Parkinson's disease.


Alfimeprase.
Alfimeprase, a fibrolase derivative with thrombolytic activity produced by recombinant DNA technology, was discovered by Amgen and was in development with Nuvelo for the treatment of stroke and catheter occlusion. However, development has been discontinued. Fibrolase is a zinc-containing metalloendopeptidase that was first isolated from the venom of the Southern copperhead snake, Agkistrodon contortrix contortrix. Alfimeprase directly degrades fibrin to break down clots. Alfimeprase is infused directly into the thrombus (side-hole catheter pushed through the entire clot) via multiple manual pulsed infusions. Alfimeprase degrades fibrin directly and entrapped blood cells are freed. Excess alfimeprase is rapidly inactivated by alpha-2 macroglobulin through an irreversible, covalent interaction. Phase III development of alfimeprase for peripheral arterial occlusion was discontinued based on poor results from the NAPA-2 and SONOMA-2 trials; however, Nuvelo resumed development of alfimeprase in 2007 for stroke and catheter occlusion.Alfimeprase's thrombolytic activity appears to be localized to the site of delivery because it is rapidly inactivated by alpha-2 macroglobulin, a naturally occurring protein in the blood, as it moves away from the site of delivery and into general blood circulation. In January 2002, Amgen and Hyseq Pharmaceuticals (now Nuvelo) entered into a collaboration to develop and commercialize alfimeprase. Nuvelo is to develop the product through clinical trials and Amgen was to be responsible for its manufacture. Both companies were to participate in commercial activities; Amgen was to have the option to lead these. Full financial terms were not disclosed. Further to this agreement, in November 2004 Amgen granted Nuvelo worldwide rights to develop and commercialize alfimeprase in exchange for milestone and royalty payments. In August 2007, Nuvelo decided to focus on core development programmes that it believed would produce the nearest-term proof-of-concept data. As a result of this realignment of organizational expenses, Nuvelo decided to continue to pursue the development of alfimeprase. In February 2003, Hyseq Pharmaceuticals merged with Variagenics Inc. to form Nuvelo Inc. In January 2006, Nuvelo and Bayer HealthCare entered a collaboration to develop and commercialize alfimeprase. Bayer was to commercialize the drug in all territories outside the US, whilst Nuvelo retains full US rights. Nuvelo was to receive other territory royalties and milestone payments to a total of $US385 million. A $US50 million upfront payment will be made to Nuvelo, while Bayer was to be responsible for 40% of the commercialization cost for global development. This partnership was to also develop stroke and deep vein thrombosis therapies. Data from the SONOMA-3 trial fell short of the company's expectations and so Nuvelo has decided to discontinue further development of alfimeprase. Nuvelo previously had decided to resume development of alfimeprase for the treatment of multiple coagulation-related disorders, including acute ischaemic stroke, catheter occlusion (CO) and acute peripheral arterial occlusion.Previously, results from the NAPA-2 (Novel Arterial Perfusion with Alfimeprase-2) trial and SONOMA-2 (Speedy Opening of Non-functional and Occluded catheters with Mini-dose Alfimeprase) phase III trial of alfimeprase in patients with acute peripheral arterial occlusion and catheter occlusion did not meet their primary endpoints. The primary endpoint of the NAPA-2 trial was the avoidance of surgery within 30 days of treatment with alfimeprase, whilst the SONOMA-2 trial's endpoint was the restoration of function at 15 minutes after dosing. In addition, these trials did not meet their secondary endpoints. As a result, Nuvelo and Bayer suspended enrolment in the NAPA-3 and SONOMA-3 phase III trials until additional analysis was complete; the SONOMA-3 trial was re-initiated. Nuvelo concluded that the delivery method for alfimeprase in the treatment of peripheral arterial occlusive disorders was suboptimal. The company closed the suspended NAPA-3 trial and planned to initiate preclinical studies focused on identifying optimized delivery methods in acute PAO in the second half of 2007. Data from the NAPA-2 trial suggested that efficacy could potentially be enhanced by maintaining alfimeprase longer at the site of the thrombus. Nuvelo's multinational phase III programme for peripheral arterial occlusion consisted of the NAPA-2 and NAPA-3 trials. Both trials were randomized, double-blind studies comparing 0.3 mg/kg of alfimeprase with placebo in a total of 600 patients in 100 centres. The primary endpoint of the NAPA-2 trial was the avoidance of surgery within 30 days of treatment; secondary endpoints included safety and pharmacoeconomics such as length of hospital and intensive care unit stay. Results from both trials have been presented. The phase II trial (NAPA-1) was completed in June 2004. This open-label, dose-escalation trial assessed the safety and efficacy of alfimeprase in 115 patients with acute peripheral arterial occlusion and was conducted in centres across the US, Europe and South Africa. Full data from the trial have been presented, which indicated that the 0.3 mg/kg dose appeared to be the optimal dose for investigation in phase III trials. In March 2003, Nuvelo announced the positive results of a phase I trial initiated in the US in July 2002; an IND was transferred from Amgen to Nuvelo in January 2002. In the SONOMA-2 trial, alfimeprase restored catheter function in patients with occluded catheters within 15 minutes with a p-value of 0.022. However, it did not meet the company's target product profile for commercial success with a p-value < 0.00125. Data from a phase II trial were presented at the 46th Annual Meeting of the American Society of Hematology held in December 2004. The study was closed in July 2004 with 55 patients enrolled. Initially the phase II study was to compare three doses of alfimeprase with the approved dose of alteplase in over 90 patients in the US. Nuvelo initiated the phase II CARNEROS-1 (Catheter Directed Alfimeprase for Restoration of Neurologic Function and Rapid Opening of Arteries in Stroke) study of alfimeprase in the treatment of acute ischaemic stroke in June 2007. CARNEROS-1 was a multicentre, open-label, dose-escalation study beginning with doses of 1, 5 and 10 mg of alfimeprase in 100 patients within 3-9 hours of stroke onset. The primary endpoints were recanalization (unblocking) of the occlusive lesion within 120 minutes of treatment, and symptomatic intracerebral haemorrhage. The first patient was dosed in December 2007; enrolment was taking place in the US and Canada. In the US, three patents have been issued relating to alfimeprase; US Patent Nos 6 261 820 (alfimeprase protein sequence), 6 440 414 (formulation of alfimeprase with a zinc stabilizer) and 6 455 269 (methods for localized administration of alfimeprase).


Equitable Science Requires Collegial Debate.
We welcome an ongoing debate about benefit-sharing related to the use of digital sequence information (DSI) and how to ensure global equity in the use of biological samples, including those donated by human beings.


[The pain situation for residents of nursing homes. Results of a study in Münster].
Little is known about the phenomenon of pain in German nursing homes. In particular, it is unknown to what extent and severity pain occurs among residents and how their pain can be described. A total of 13 nursing homes located in the city of Münster, Germany, were included as part of the health services research project "Action Alliance Pain-free City Münster." Data were collected from 436 residents over 65 years old via self-report or the observational pain tool pain assessment in advanced dementia, german version (PAINAD-G), according to the cognitive status of the residents. At the time of the interview, the majority of the residents questioned reported suffering from pain at rest and/or during movement. Approximately one quarter of residents complained about moderate to intolerable pain at rest and nearly 45% during movement. Residents encountered pain most often when standing up, sitting, resting in bed and walking and three quarters of residents had suffered from pain for more than 1 year. Many residents experienced pain in several body regions. Among residents assessed solely by the observational pain scale PAINAD-G, signs indicating pain existed in 21% (≥ 6) or 69% (≥ 2), respectively, depending on the cut-off value chosen on the PAINAD-G scale. Pain in nursing homes is a challenge that needs more attention as it has considerable negative consequences for the persons concerned. The extent of pain in the studied facilities indicates an urgent need for action on the part of all professionals caring for residents in nursing homes.


Incidence and risk factors for polypharmacy among elderly people assisted by primary health care in Brazil.
Polypharmacy is recognized as a global public health problem and one of the greatest challenges related to the aging population. Few studies have investigated the incidence and risk factors for polypharmacy among elderly individuals. These studies provided important information on the issue but were developed in high-income countries. This study investigates the incidence and risk factors for polypharmacy among elderly people assisted by primary health care over a period of 11 years. This was a census-based prospective longitudinal study that included people aged 60 years or older living in a small municipality in the state of Rio Grande do Sul, Brazil. The baseline occurred in 2010 and the second wave of the study occurred in 2021. The study population consisted of elderly individuals who did not use polypharmacy at baseline and were reinterviewed in 2021 (N = 128). Data collection in the first and second waves was performed through a household survey using a structured questionnaire. The dependent variable was polypharmacy, defined as the simultaneous use of 5 or more drugs. The independent variables included sociodemographic, health and functionality factors. For multivariate analyses, Poisson regression with robust variance was used, estimating the relative risk and 95% confidence intervals. The incidence of polypharmacy was 46.1% in the 11-year period. The highest number of health problems was a risk factor for polypharmacy (RR = 1.177; 95% CI 1.093-1.267). The incidence of polypharmacy among elderly people assisted in primary health care in Brazil is high. The number of diseases is a risk factor for polypharmacy. These results have implications for future primary health care practices and may support the development of policies, actions and services aimed at reducing polypharmacy and promoting the rational use of drugs in the population at higher risk.


Sequences upstream of the-35 hexamer of rrnB P1 affect promoter strength and upstream activation.
Transcription from Escherichia coli ribosomal RNA promoters is increased about 20-fold in vivo by a DNA sequence (the Upstream Activation Region, UAR) located upstream of the -35 conserved hexamer. The UAR stimulates transcription through two mechanisms: one which involves binding of the Fis protein to the UAR, and another mechanisms which functions in the absence of additional protein factors. We have previously constructed a collection of mutations in the region upstream of the -35 hexamer of rrnB P1. Most of these mutations have either no effect on promoter activity or decrease activity 2-5-fold in vivo (Gaal, T., Barkei, J., Dickson, R.R., De Boer, H.A., De Haseth, P.L., Alavi, H. and Gourse, R.L.(1989) J. Bacteriol. 171, 4852-4861). Two mutations leave both the -35 consensus hexamer and the Fis binding consensus sequence intact, yet have larger (14-50-fold) effects on transcription. One substitution just upstream of the -35 hexamer (a C to T change at position -37) primarily affects intrinsic promoter strength, leaving the UAR functional. On the other hand, a three base pair deletion (bases -38 through -40) severely reduces UAR-mediated activity. A substitution covering the three base pair deletion was constructed and found to be activated normally. UAR function appears dependent on its position relative to the RNA polymerase binding site, suggesting that a particular spatial geometry may be necessary for Fis-dependent and/or factor-independent activation to occur.


'Your mascara is running'.
Chromhidrosis is a rare disorder, which can have significant psychosocial consequences for patients, particularly when it affects the face, as it can be mistaken for scarring, dirt or erroneous make-up application. Chromhidrosis can be divided into apocrine, eccrine and pseudo subtypes. We present a case of apocrine chromhidrosis localized to the bilateral cheek area. Click https://www.wileyhealthlearning.com/#/online-courses/9c761d0a-20de-4709-a57d-36be93cf64e1 for the corresponding questions to this CME article.


Soft and hard tissue correction of facial deformity associated with bilateral temporomandibular joint ankylosis.
Bilateral temporomandibular joint ankylosis in childhood can result in severe facial deformity characterized by both hard and soft tissue changes. The soft tissue deformity manifests as a submental hump of redundant soft tissue which has been displaced inferiorly due to deficiency of skeletal attachments. Improved results can be produced in these cases if the orthognathic correction is complemented by correction of the soft tissues. The presence of microgenia makes it possible to reach the subplatysmal plane through an intraoral incision allowing for the plication of platysma and relocation of the displaced soft tissues from the cervical to the mental region.


Analysis of perfluorooctanoate (PFOA) and other perfluorinated compounds (PFCs) in the River Po watershed in N-Italy.
C7-C11 perfluorinated carboxylates (PFACs) and perfluorooctansulfonate (PFOS) were analysed in selected stretches of the River Po and its major tributaries. Analyses were performed by solid-phase extraction (SPE) with Oasis HLB cartridges and methanol elution followed by LC-MS-MS detection using 13C-labelled internal standards. High concentration levels ( approximately 1.3 microg l(-1)) of perfluorooctanoate (PFOA) were detected in the Tánaro River close to the city Alessandria. After this tributary, levels between 60 and 337 ng l(-1) were measured in the Po River on several occasions. The PFOA concentration close to the river mouth in Ferrara was between 60 and 174 ng l(-1). Using the river discharge flow data in m3 s(-1) at this point (average approximately 920 m3 s(-1) for the year 2006), a mass load of approximately 0.3 kg PFOA per hour or approximately 2.6 tons per year discharged in the Adriatic Sea has been calculated. PFOS concentration levels in the Po River at Ferrara were approximately 10 ng l(-1).


PlantCADB: A Comprehensive Plant Chromatin Accessibility Database.
Chromatin accessibility landscapes are essential for detecting regulatory elements, illustrating the corresponding regulatory networks, and, ultimately, understanding the molecular basis underlying key biological processes. With the advancement of sequencing technologies, a large volume of chromatin accessibility data has been accumulated and integrated for humans and other mammals. These data have greatly advanced the study of disease pathogenesis, cancer survival prognosis, and tissue development. To advance the understanding of molecular mechanisms regulating plant key traits and biological processes, we developed a comprehensive plant chromatin accessibility database (PlantCADB) from 649 samples of 37 species. These samples are abiotic stress-related (such as heat, cold, drought, and salt; 159 samples), development-related (232 samples), and/or tissue-specific (376 samples). Overall, 18,339,426 accessible chromatin regions (ACRs) were compiled. These ACRs were annotated with genomic information, associated genes, transcription factor footprint, motif, and single-nucleotide polymorphisms (SNPs). Additionally, PlantCADB provides various tools to visualize ACRs and corresponding annotations. It thus forms an integrated, annotated, and analyzed plant-related chromatin accessibility resource, which can aid in better understanding genetic regulatory networks underlying development, important traits, stress adaptations, and evolution.PlantCADB is freely available at https://bioinfor.nefu.edu.cn/PlantCADB/.


Recent advances in applications of power ultrasound for petroleum industry.
Power ultrasound, as an emerging green technology has received increasing attention of the petroleum industry. The physical and chemical effects of the periodic oscillation and implosion of acoustic cavitation bubbles can be employed to perform a variety of functions. Herein, the mechanisms and effects of acoustic cavitation are presented. In addition, the applications of power ultrasound in the petroleum industry are discussed in detail, including enhanced oil recovery, oil sand extraction, demulsification, viscosity reduction, oily wastewater treatment and oily sludge treatment. From the perspective of industrial background, key issue and resolution mechanism, current applications and future development of power ultrasound are discussed. In addition, the effects of acoustic parameters on treatment efficiency, such as frequency, acoustic intensity and treatment time are analyzed. Finally, the challenges and outlook for industrial application of power ultrasound are discussed.


Transdiagnostic comparisons of intellectual abilities and work outcome in patients with mental disorders: multicentre study.
Cognitive impairment is common in people with mental disorders, leading to transdiagnostic classification based on cognitive characteristics. However, few studies have used this approach for intellectual abilities and functional outcomes. The present study aimed to classify people with mental disorders based on intellectual abilities and functional outcomes in a data-driven manner. Seven hundred and forty-nine patients diagnosed with schizophrenia, bipolar disorder, major depression disorder or autism spectrum disorder and 1030 healthy control subjects were recruited from facilities in various regions of Japan. Two independent k-means cluster analyses were performed. First, intelligence variables (current estimated IQ, premorbid IQ, and IQ discrepancy) were included. Second, number of work hours per week was included instead of premorbid IQ. Four clusters were identified in the two analyses. These clusters were specifically characterised in terms of IQ discrepancy in the first cluster analysis, whereas the work variable was the most salient feature in the second cluster analysis. Distributions of clinical diagnoses in the two cluster analyses showed that all diagnoses were unevenly represented across the clusters. Intellectual abilities and work outcomes are effective classifiers in transdiagnostic approaches. The results of our study also suggest the importance of diagnosis-specific strategies to support functional recovery in people with mental disorders.


Application of the core competencies after unexpected patient death: consolation of the grieved.
To review and assess educational strategies and formats regarding communication with families/survivors in the aftermath of unexpected and untimely patient death. To propose an integrated curriculum designed and intended to foster proficiency, competence, confidence, and composure in relaying catastrophic information in the context of the professional experience of a cohort of seasoned surgeons. Unexpected and untimely patient death is emotionally and psychologically wrenching for families, surgeons, and healthcare providers. We have previously proffered that 2 distinct, but interactive, phases of response are relevant when communicating with a family before and after the event: a proactive phase intended to establish a positive therapeutic relationship with the family; and a reactive phase intended to respond to the family in a compassionate and respectful manner and to ensure self-care for the physicians and health care providers. Survey of a cohort of senior surgeons (membership of the Southern Surgical Association) and Surgical Residency Program Directors (membership of the Association of Program Directors in Surgery). Sixty percent of the senior surgeons surveyed had experienced unexpected patient death. They advised strategies to cope with that clinical situation commensurate with the core competencies of the Accreditation Council for Graduate Medical Education: Medical Knowledge: maximize objective information/data and minimize subjective opinion; Patient Care: critique the events and conduct postmortem analyses; Interpersonal and Communication Skills: honesty, empathy, and patience; Professionalism: provide emotional and psychological support to family and personnel with privacy and in a nonaccusatory manner; Practice-Based Learning and Improvement: preoperative discussion and documentation in the context of informed consent and advanced directives vis-á-vis risk-benefit, effort-yield, and benefit-burden analyses; and Systems-Based Practice: involve chaplains and hospital personnel. Thirty-six percent of the graduate surgical educational programs surveyed allegedly provided educational venues to enable surgical residents to cope with unexpected patient death, although the formats were not specified. Graduate, postgraduate, and continuing educational programs aspire to prepare physicians and surgeons for independent professional practice-scientifically, humanistically, and artistically. Incorporating educational strategies to enable graduates to cope with the emotional and psychological turmoil of unexpected patient death is relevant.


Alaria alata mesocercariae prevalence and predilection sites in amphibians in Latvia.
Alaria alata is known as a trematode with a complex life cycle. The trematode Alaria alata infects amphibians as second intermediate hosts. In the present study, we examined 390 amphibians-European water frogs Pelophylax esculentus complex (n = 335), common frogs Rana temporaria (n = 19), moor frogs Rana arvalis (n = 3), and common toads Bufo bufo (n = 30) collected from randomly selected wetland habitats in Latvia. Out of all examined specimens, 80 were tadpoles and 310 were adult amphibians. Mesocercariae of A. alata was detected in 108 specimens from all examined amphibian species, except the common toad, reaching the overall prevalence of 27.7%. Tadpoles were found to be more frequently infected with A. alata, when compared with adults, 58.8% and 22.4%, respectively. The results showed that mesocercariae accumulate in visceral membranes, different internal organs, and muscles in the head area. This is a comprehensive study to identify A. alata mesocercariae predilection sites in amphibians.


Using Stretchable PPy@PVA Composites as a High-Sensitivity Strain Sensor To Monitor Minute Motion.
With the rapid development of flexible and wearable electronic devices, research on high-sensitivity strain sensors has been attracting much attention. Here, glutaraldehyde is used as a cross-linking reagent to precross-link poly(vinyl alcohol); then FeCl3·6H2O is added into the precross-linked poly(vinyl alcohol) to obtain composite films of FeCl3@PVA after gelatinization and freeze drying. Elastic conductive films of polypyrrole@poly(vinyl alcohol) (PPy@PVA) are prepared by immersing FeCl3@PVA into a solution of pyrrole in acetonitrile and water to complete the polymerization in situ. The effects of the concentrations of glutaraldehyde and FeCl3·6H2O on the film's structure and properties have been studied in detail; the results show that the strain sensor prepared from the optimized film has excellent stretchability (strain up to 309.5%), mechanical property (tensile strength of 32.8 MPa), and relatively high sensitivity (gauge factor can reach 5.07 under 1.0% strain). It can be used to detect various tiny physiological signals, for example, detecting the number of pulse beats, bending of the knuckles at different frequencies, and recognizing the pronunciation of different words by vocal cord vibration. These good properties mean that this kind of PPy@PVA strain sensor has great application prospects in physiological monitoring.


Parasomnias.
This article presents four examples of parasomnia activity. Sleepwalking, sleep terror, and rhythmic movement disorder all occur more commonly in children; however, they can persist into adulthood. REM behavior disorder frequently occurs in elderly patients with neurologic lesions. The sleep stage associations of the different disorders differ. Two of the disorders, sleepwalking and sleep terrors, have a clear association with stage 3/4 sleep, and REM behavior disorder occurs in REM sleep. Rhythmic movement disorder episodes can present solely in REM sleep but more typically occur in light non-REM sleep, and there are usually voluntary episodes during wakefulness.


Incidence, Presentation, and Risk Factors for Sodium Valproate-Associated Hyperammonemia in Neurosurgical Patients: A Prospective, Observational Study.
Sodium valproate (VPA) is a commonly prescribed antiepileptic drug (AED) in daily neurosurgical practice. However, the incidence of VPA-associated hyperammonemia (VAH) and its life-threatening consequence, VPA-induced hyperammonemic encephalopathy (VHE), in neurosurgical patients is unknown. We determined the incidence, clinical presentation, and risk factors for VAH. This prospective cohort study was performed on adult neurosurgical patients prescribed VPA for at least a week over a 22-month period. Blood tests for ammonia, VPA, and liver function were performed at the time of recruitment. The primary end point was VAH. Secondary end points were VHE and liver dysfunction. In total, 252 patients were recruited. The commonest disease etiology was brain tumors (27%, 69), followed by aneurysmal subarachnoid hemorrhage (SAH; 26%, 65). VPA was prescribed for primary seizure prophylaxis in 110 patients (44%). The mean daily dose was 1148 mg for a mean duration of 48 months. The mean serum VPA level was 417 μmol/L. In total, 92 patients (37%) were prescribed an additional AED, the most common being phenytoin (65%, 60/92). The mean serum ammonia level was 47 μmol/L. In total, 28% (71/252) of patients had VAH and only 0.7% had VHE. Independent factors were aneurysmal SAH (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI] 1.1-4.2), concomitant phenytoin (aOR 1.9; 95% CI 1.0-3.5), and phenobarbital (aOR 4.6; 95% CI 1.1-20.0). No associations with VPA dose, duration, serum levels, and liver function were observed. Although VAH is common among neurosurgical patients, VHE is rare. Patients with aneurysmal SAH or on concomitant enzyme-inducing AEDs are at risk. Clinicians should be vigilant for VHE symptoms in these patients.


Factors affecting ability to resume oral nutrition in the oropharyngeal dysphagic individual.
Successful oral intake of nutrition depends not only on the patient's ability to swallow efficiently and safely but also a number of cognitive, neurolinguistic, and behavioral variables. This paper reviews these competencies as they are integrated into the act of oral feeding and describes the types of disorders that affect these abilities. Methods of evaluating and treating the abilities needed for successful oral intake are described.


Relation of renal thromboxane A2 production to urine flow, electrolyte excretion and plasma renin activity in control state and drug induced hypotension.
The functional importance of renal TxB2 generation in the maintenance of elevated arterial blood pressure in essential hypertension was followed in 22 patients, using the method of sustained blood pressure decrease by i.v. sodium nitroprusside infusion. Linear correlation between urinary excretion of TxB2, urine flow, and sodium excretion could be established in both control and hypotensive periods. Presumably, changes in urinary excretion of TxB2 reflect a secondary intrarenal counterregulatory response.


[Analysis of loss of heterozygosity on chromosome 8 in human prostate carcinoma and high grade prostatic intraepithelial neoplasia].
To detect the status of loss of heterozygosity (LOH) on chromosome 8 in prostate carcinoma and high grade prostatic intraepithelial neoplasia (PIN). Pure DNA was obtained from prostate neoplasms and normal tissues by tissue microdissection. LOH on chromosome 8 was detected by PCR based microsatellite polymorphism analysis technique using 14 pairs of microsatellite primers in 10 samples of prostate carcinoma and 10 samples of high grade PIN. There were different frequencies of LOH on chromosome 8 in 10 samples of prostate carcinoma. 8p23.1-p23.2 and 8p21-p22 were two high-frequency LOH regions. LOH on chromosome 8 was detected in 3 samples of high grade PIN. There were high-frequency LOH regions on chromosome 8 of prostate carcinoma, located on 8p23.1-p23.2 and 8p21-p22. High grade PIN and prostate carcinoma share the same allelic loss on 8p. Tumor suppressor genes located at these two regions may be potentially involved in the initiation and progression of prostate carcinoma.


Comparative analysis and natural evolution of squalene epoxidase in three Fritillaria species.
Fritillariae Bulbus are the most commonly used antitussive and edible herbs in China. Based on UPLC-QTOF-MS and UPLC-QQQ-MS, the validated MRM-based non-targeted quantitative method was applied to determinate the contents of 48 Fritillaria alkaloids (FAs) in three Fritillaria species (F. thunbergii Miq., F. unibracteata and F. ussuriensis). The RNA-Seq results showed that gene transcript levels have different expression patterns in three Fritillaria species. Based on transcriptome data, the full-length cDNA sequences of squalene epoxidase gene were cloned and characterized. Natural evolution of squalene epoxidase genes resulted in four mutations (C236R, M489L, G510A and K517R) in three Fritillaria species. Molecular docking analysis showed that the 236 residue is located inside the pocket and the binding center while other three residues are located on the surface of the protein. Functional verification indicated the mutations of SQE (C236R) could effectively increase the activity of SQE and obtain higher yield of 2,3-oxidosqualene in recombinant yeast. And the mutations of SQE (M489L and G510A), which increased the hydrophobicity of the protein surface, could also enhance the activity of SQE. This study provides major insights into the metabolites differentiation of FAs biosynthesis, and a firm foundation for the quality control and metabolic engineering of Fritillariae bulbus.


[The study of risk ratio on genetic factors in recurrent aphthous ulcer].
To study the relation of SCE, MNR, CAR of lymphocytes in RAU patients and RAU. SCE, MNR, CAR of 60 RAU patients were determined, and were analyzed by non-condition Logistic regression and the risk ratio of the 3 studying factors was calculated. SCE, MNR and CAR were important risk factors among many complicated causes of RAU. The results of the study showed essentially that RAU patients could have some pathological genetic predisposition and abnormal genetic materials congenitally.


Capacity to Consent for Treatment in Patients with Psychotic Disorder: A Cross-Sectional Study from North Karnataka.
Recently, the Mental Healthcare Act (MHCA) 2017 was introduced in India. Being a right-based act, it has made the assessment of the capacity to consent an integral part of clinical work. To the best of our knowledge, there are no Indian studies on this topic. Hence, this study aimed to assess the capacity to consent to mental healthcare and treatment in patients with functional psychosis and the factors affecting the same. This cross-sectional study included participants with the ICD-10 DCR diagnosis of a psychotic disorder admitted in the psychiatry ward of a tertiary health care center in Karnataka, India. MacArthur Competence Assessment Tool for Treatment was used to assess the capacity to consent to treatment. Brief Psychiatric Rating Scale (BPRS) and the Beck Cognitive Insight Scale were applied to assess the severity of psychosis and level of insight, respectively. A hundred participants were recruited. Twenty-four were found to have an intact capacity to consent to treatment. High BPRS scores (P value = 0.0002) and low insight scores (P value = 0.0002) were associated with an impaired capacity. About one-fourth of participants had an intact capacity to consent to treatment. Higher severity of psychosis and a poorer insight into the illness were associated with impaired capacity to consent.