The canine lymphocyte: effect of streptolysin O on the proliferative response of canine lymphocytes.
The effects of Streptolysin O (SLO) on canine peripheral blood lymphocytes were studied using the lymphocyte blastogenesis test (LBT). Canine lymphocytes stimulated with SLO produced a response that was similar to the response obtained with the commonly used phytomitogens: phytohemagglutinin (PHA), concanavalin A (CON A) and pokeweed mitogen (PWM). When SLO was added to any of the phytomitogens and incubated with canine lymphocytes, an additive or stimulatory response was obtained. However, mixing the phytomitogens in any combination did not produce a similar additive or stimulatory response. The results were interpreted to mean that in the canine system, the binding of SLO to lymphocytes does not sterically interfere with receptors for PHA, CON A, or PWM. Additionally, SLO may stimulate a population of lymphocytes that is distinct from that stimulated by the phytomitogens. Moreover, it would appear that the phytomitogens probably stimulate the same or an overlapping population of lymphocytes. Experiments using enriched lymphoid cell populations were used to characterize the lymphocytes stimulated by phytomitogens and SLO. Lipopolysaccharides from two different bacteria were unable to cause a significant lymphoproliferative response.


Nucleotide composition of the Zika virus RNA genome and its codon usage.
RNA viruses have genomes with a distinct nucleotide composition and codon usage. We present the global characteristics of the RNA genome of Zika virus (ZIKV), an emerging pathogen within the Flavivirus genus. ZIKV was first isolated in 1947 in Uganda, caused a widespread epidemic in South and Central America and the Caribbean in 2015 and has recently been associated with microcephaly in newborns. The nearly 11 kb positive-stranded RNA genome of ZIKV was analyzed for its nucleotide composition, also in the context of the folded RNA molecule. Nucleotide trends were investigated along the genome length by skew analyses and we analyzed the codons used for translation of the ZIKV proteins. ZIKV RNA has a biased nucleotide composition in being purine-rich and pyrimidine-poor. This preference for purines is a general characteristic of the mosquito-borne and tick-borne flaviviruses. The virus-specific nucleotide bias is further enriched in the unpaired, single-stranded regions of the structured ZIKV RNA genome, thus further imposing this ZIKV-specific signature. The codons used for translation of the ZIKV proteins is also unusual, but we show that it is the underlying bias in nucleotide composition of the viral RNA that largely dictates these codon preferences. The ZIKV RNA genome has a biased nucleotide composition that dictates the codon usage of this flavivirus. We discuss the evolutionary scenarios and molecular mechanisms that may be responsible for these distinctive ZIKV RNA genome features.


Cushing's syndrome: a tripartite entity.
The three distinct etiologies of Cushing's syndrome usually reflect the presence of a neoplasm, most often but not necessarily of the pituitary, and all ultimately result in hypercortisolism. Recent advances in diagnosis and treatment have vastly improved the outlook for many patients. Several therapeutic options are outlined, the success of which depends on accurate identification of the cause of hypercortisolism.


The formation and structure of some proteose-peptone components.
Two constituents of the proteose-peptone fraction of bovine milk have been isolated and characterized. Component 5 (PP5) has been shown to represent residues 1-105 and 1-107 of the beta-casein amino acid sequence, while component 8-fast (PP8F) corresponds to residues 1-28 of beta-casein. Thus, these proteose-peptones represent the N-terminal portions of the beta-casein molecule, produced by proteolytic cleavages which form the gamma 1, gamma 2 and gamma 3-caseins from the C-terminal part. The continuing formation of the total proteose-peptone fraction, PP5, PP8F and the gamma-caseins during storage of raw milk at 18 or 37 degrees C has been also been demonstrated.


Life Long Learning: The Attending and Educator in Orthopedic Trauma.
As effective surgeon educators, we must seek continual improvement, to be "better today than I was yesterday." This pursuit of personal and professional development requires self-awareness of a guiding purpose, and grit, the passion and perseverance to achieve long-term goals. Surgical training draws on an apprenticeship model, where progressive transfer of knowledge, responsibility, and autonomy occurs over time as trainees work with experienced surgeons. Educators should model personal responsibility and technical excellence and require both of their trainees. While training programs shift towards competency-based learning, educators must remember that we shape learners with the "hidden curriculum" and not just the facts we teach them.


Pulmonary tuberculosis associated acute fibrinous and organizing pneumonia: A case report and literature review.
Acute fibrinous and organizing pneumonia (AFOP) is a rare histological interstitial pneumonia pattern characterized by patches of "fibrin balls" distributed within the alveoli and organizing pneumonia. Currently, there is no consensus on the diagnosis and treatment of this disease. We present the case of a 44-year-old male with AFOP secondary to Mycobacterium tuberculosis. We have further reviewed organizing pneumonia (OP) and AFOP caused by tuberculosis. Tuberculosis secondary to OP or AFOP is rare and challenging to diagnose. We need to constantly adjust the treatment plan based on the patient's symptoms, test results, and response to treatment in order to arrive at an accurate diagnosis and maximize treatment efficacy.


Autogenous particulated dentin for alveolar ridge preservation. A systematic review.
This review aimed to investigate the clinical outcomes of autogenous particulated dentin (APD) used for alveolar ridge preservation (ARP), evaluating volume gain, histologic/histomorphometric data, and associated complications. The review followed PRISMA guidelines and was registered in the International Prospective Register of Systematic Reviews (PROSPERO). An automated search was made in four databases (Medline/Pubmed, Scopus, Web of Science, and Cochrane Library) supplemented by a manual search for relevant clinical articles published before March 10th, 2022. The review included human studies of at least four patients in which extraction and subsequent ARP were performed in a single surgery. Both comparative studies and studies that assessed ARP with APD exclusively were admitted. The quality of evidence was assessed with the Cochrane bias assessment tool, the Newcastle-Ottawa Quality Assessment Scale, and the Joanna Briggs Institute Critical Appraisal tool. Eleven studies fulfilled the inclusion criteria and were included for descriptive analysis, with a total of 215 patients, and 337 alveoli preserved by APD, spontaneous healing (blood clot), or other bone substitutes, obtaining comparatively less vertical and horizontal resorption when APD was used. After dental extraction, autogenous dentin was effective in terms of volume maintenance, showing promising results in histologic/histomorphometric analysis, and a low complication rate. Nevertheless, few comparative studies with comparable parameters have been published and so more research providing long-term data is needed to confirm these findings.


Antibiotic use for viral acute respiratory tract infections remains common.
To determine the type and number of antibiotic prescriptions filled in the 28 days following an index visit for acute respiratory tract infections (ARTIs) generally presumed to be viral. This was a secondary analysis of administrative data. We linked administrative data for pharmacy, clinical encounters, and providers to identify all prescriptions for a relevant antibiotic filled within 28 days of an index visit for an ARTI. Data were analyzed descriptively. The primary outcome was whether or not the patient was prescribed an antibiotic or anti-influenza medication for an episode of presumed viral ARTI. There were 54,656 encounters for presumed viral ARTI. Most visits (84.4%) were to a primary care clinician, with 12% to an urgent care center and 3.6% to the emergency department. Within 28 days of an encounter for a presumed viral upper respiratory tract infection, 49.4% of patients filled an initial antibiotic prescription, 4.8% a prescription for an anti-influenza drug, and 1.2% received both. A second antibiotic prescription was filled after the initial prescription by 8.9% of patients, and a third by 0.7%. Antibiotic use was most common for acute bronchitis (67.8%) and in the urgent care setting (60.2%). Antibiotics were prescribed less often by pediatricians, whereas anti-influenza medications were prescribed most often for patients aged 5 to 17 years by both pediatricians and family physicians. Antibiotic use has increased since 2007, when azithromycin became a generic drug. Prescribing antibiotics for ARTIs that are likely to be viral in origin remains common, despite extensive public health educational efforts.


Update on incidence of inpatient tubal ligation and long-acting reversible contraception in the United States.
Inpatient insertion of long-acting reversible contraception and immediate postpartum tubal ligation allow women to initiate highly effective contraception before hospital discharge. We measured rates of intrauterine device and contraceptive implant initiation and tubal ligations performed during delivery hospitalizations from 2016 to 2018 from a representative sample of US hospital discharges. We used the 2016 to 2018 National Inpatient Sample database, a 20% sample of all community hospital discharges in the United States, to identify delivery hospitalizations with concomitant intrauterine device insertion, contraceptive implant insertion, or tubal ligation. We performed weighted multivariable logistic regression to examine associations between possible predictors (age, delivery mode, payer, geographic region, and year) and odds of long-acting reversible contraception and tubal ligation, and to compare characteristics of users. This sample included 2,216,638 discharges, representing 20% of 11,083,180 delivery hospitalizations across the United States. Intrauterine device insertion increased from 2.2 per 1000 deliveries (2016) to approximately 5.0 per 1000 deliveries (2018; P<.0001); implant insertion increased from 0.3 per 1000 deliveries (2016) to 2.5 per 1000 deliveries (2018; P<.0001); tubal ligation procedures decreased (64.2 to 62.1 per 1000 deliveries; P<.0001). Women who underwent a cesarean delivery had higher odds of having a tubal ligation than those who had a vaginal delivery (adjusted odds ratio, 8.83; 95% confidence interval, 8.73-8.97). Women aged <25 years had 7 times higher odds of receiving long-acting reversible contraception than of receiving tubal ligation (adjusted odds ratio, 7.38; 95% confidence interval, 6.90-7.90). Women with public insurance had almost 5 times the odds of receiving long-acting reversible contraception compared with those with commercial insurance (adjusted odds ratio, 4.83; 95% confidence interval, 4.59-5.06). Rates of long-acting reversible contraception insertion continue to increase while the rates of inpatient postpartum tubal ligations slowly decline. Variations in patient characteristics are associated with receiving long-acting reversible contraception or tubal ligation.


Aflatoxicosis in rabbits: Effectiveness of Egyptian raw bentonite in prevention or diminution the detrimental effects of naturally aflatoxin contaminated diets.
Thirty five females and 15 males of New Zealand White mature rabbits about 6 months of age, were assigned to 1-5 dietary treatments (7 does+3 bucks for each): uncontaminated control diet, naturally aflatoxin contaminated diet without or with 1,2 and 3% bentonite. Rabbit fed with the aflatoxin-diet had a decreased (P<0.01 or 0.05) physical semen characteristics of bucks and a reproductive performance traits of does. The values of conception rate (%), gestation length (days), litter size (n) and litter weights (g) at birth and viability (%) of litters of doe rabbits, fed with the aflatoxin-diet, recorded, respectively: 64.5; 31.0; 4.4; 275.0 and 57.1 versus 85.6; 30.3; 7.9; 508.0; and 100 for those fed with the uncontaminated diet. Addition of bentonite to the aflatoxin contaminated diet improved in general the physical semen characteristics of buck and reproductive performance traits of doe rabbits. The results of the study demonstrate that adding 1% of Egyptian raw bentonite to the naturally aflatoxin contaminated rabbit diets can provide an effective, cheap and safe practical technique for preventing the aflatoxicosis in mature rabbits.


delta9-tetrahydrocannabinol and the hippocampus: effects on CA1 field potentials in rats.
The effects of delta9-tetrahydrocannabinol (THC) on ortho- and antidromically elicited CA1 field potentials were observed in locally anesthetized rats and in anesthetized with urethane. THC augmented amplitudes of population EPSP's as well as orthodromic and antidromic population spikes from pyramidal cells in locally anesthetized animals. Latencies to peak amplitude of these response were increased. Conditioning-test shock experiments revealed taht THC also depressed recurrent inhibition probably mediated by basket cells. In animals under urethane anesthesia THC enhanced test responses, but failed to augment population response to the conditioning stimulus. It was concluded that THC enhanced postsynaptic excitatory processes but attenuated recurrent inhibition. Urethane anesthesia completely blocked the postsynaptic excitatory effect of THC but had little apparent influence on THC's disinhibitory action.


Dietary protein intake and all-cause mortality: results from The Kawasaki Aging and Wellbeing Project.
Increased protein intake has been recommended to prevent sarcopenia/frailty, reports on the quantity and quality of protein intake needed and the associated prognosis, particularly in the aging population of Asia, are limited. In this study, we aimed to investigate the relationship between protein intake and mortality in Japanese individuals, aged 85 years and older. The data were obtained from The Kawasaki Aging and Wellbeing Project, which is a prospective cohort study of older adults aged between 85 and 89 years with no physical disability at baseline. Of the 1,026 adults in the cohort, 833 were included in the analysis, after excluding those who had not completed a brief, self-administered diet history questionnaire or those who scored less than 24 on the Mini-Mental State Examination. The participants were grouped into quartiles based on protein intake: Q1 (protein < 14.7, %Energy), Q2 (14.7 ≤ protein < 16.7, %Energy), Q3 (16.7 ≤ protein < 19.1, %Energy), and Q4 (≥ 19.1, %Energy). Multivariate Cox proportional hazards models were utilized to evaluate the association between protein intake and all-cause mortality. Kaplan-Meier survival curves were employed to investigate the relationship between protein intake and all-cause mortality. The mean protein intake of our study population was 17.0% of total energy. Animal protein intake, particularly fish intake, increased significantly along with total protein intake. The study had an average observation period of 1,218 days and recorded 89 deaths. After adjusting for age, sex, skeletal muscle mass index, cardiovascular disease, cancer, education, and serum albumin levels, a lower risk of all-cause mortality was observed in the highest protein intake (Q4) group than in the lowest protein intake (Q1) group (hazard ratio: 0.44, 95% confidence interval: 0.22-0.90, p-value: 0.020). Protein intake is associated with a reduced risk of all-cause mortality in older adults (aged ≥ 85 years) who engage in independent activities of daily living. This association may impact all-cause mortality independent of muscle mass.


The combined tool approach for face mask removal during on-field conditions.
An effective approach to emergency removal of the face mask (FM) from a football helmet should include successful removal of the FM and limitation of both the time required and the movement created during the process. Current recommendations and practice are to use a cutting tool to remove the FM. Researchers recently have suggested an alternate approach that combines the use of a cordless screwdriver and a cutting tool. This combined tool approach has not been studied, and FM removal has not been studied in a practical setting. To investigate the effectiveness and speed of using a combined tool approach to remove the FMs from football helmets during on-field conditions throughout the course of a football season. Randomized multigroup design. Practice field of 1 National Collegiate Athletic Association Division II football college. Eighty-four members of 1 football team. We used a battery-operated screwdriver for FM removal and resorted to using a cutting tool as needed. We tracked FM removal success and failure and trial time and compared results based on helmet characteristics, weather variables, and the seasonal timing of the removal trial. Of the 84 players, 76 were available for data-collection trials. Overall, 98.6% (75/76) of FM removal trials were successful and resulted in a mean removal time of 40.09 +/- 15.1 seconds. We found no differences in FM removal time throughout the course of the season. No differences in effectiveness or trial time were found among helmet characteristics, weather variables, or the timing of the trial. Combining the cordless screwdriver and cutting tool provided a fast and reliable means of on-field FM removal in this Division II setting. Despite the excellent overall result, 1 FM was not removed in a timely manner. Therefore, we recommend that athletic trainers practice helmet removal to be prepared should FM removal fail.


Meeting the public health challenge of protecting private wells: Proceedings and recommendations from an expert panel workshop.
Private wells serving fewer than 25 people are federally unregulated, and their users may be exposed to naturally occurring agents of concern such as arsenic and radionuclides, as well as anthropogenic contaminants. The Centers for Disease Control and Prevention's Clean Water for Health Program works to protect private wells and prevent adverse health outcomes for the roughly 15% of Americans who rely on them. To understand current and emerging challenges to the private drinking water supply, an interdisciplinary expert panel workshop on "Future and Emerging Issues for Private Wells" was organized to inform strategic planning for the Clean Water for Health Program. The panel assessed current conditions of ground water as a source for private wells, identified emerging threats, critical gaps in knowledge, and public health needs, and recommended strategies to guide future activities to ensure the safety of private drinking water wells. These strategies addressed topics of broad interest to the environmental public health community including: development of new methods to support citizen science; addressing contaminant mixtures; expanding capacity for well testing; evaluating treatment technologies; building an evidence base on best practices on well owner outreach and stewardship; and research and data needs.


Broken guide wire--a fault of design?
To report a potentially serious complication resulting from a faulty guide wire during central venous catheterization. We report breakage of a guide wire with potential severe implications for a 47-yr-old critical care patient. The tip of the J-wire became lodged in the internal jugular vein, and required fluoroscopic guidance for removal, which occurred without complication. Breakage of a guide wire during central venous catheter insertion has been very rarely reported. However, inherent faults in design or in the manufacturing process of the guide wire could lead to this rare complication. A simple bedside test is proposed to detect breakage in the core section of the guide wire.


Mesothelin levels in urine are affected by glomerular leakage and tubular reabsorption.
Mesothelin is a soluble biomarker of malignant mesothelioma. Levels in serum, however, are also influenced by other factors, including age and glomerular filtration rate (GFR). The measurement of mesothelin in urine has recently gained interest, but the renal handling of this protein has not been sufficiently examined. A total of 75 patients with benign kidney disease were prospectively included in the study. Mesothelin levels were measured in the serum and in the urine of all the participants by using enzyme-linked immunosorbent assay. Urinary albumin and alpha 1-microglobulin (A1M) levels, which are markers of glomerular leakage and of decreased tubular reabsorption, respectively, and the estimated GFR (eGFR) of each participant were obtained. All urine analyte levels were standardized (std) against urinary creatinine levels. Absolute mesothelin levels in urine (median, 0.58 nmol/L; interquartile range [IQR], 0.25-1.03 nmol/L) were significantly lower than those in serum (median, 1.74 nmol/L; IQR, 1.35-2.43 nmol/L; P < .001). Urinary mesothelin(std) levels positively correlated with serum mesothelin (r = 0.35, P < .01), albumin(std) (r = 0.51, P < .001), and A1M(std) levels (r = 0.71, P < .001). Neither age nor eGFR were associated with urinary mesothelin(std) levels. Similarly, multiple linear regression analysis indicated that only albumin(std) and A1M(std) levels were significantly positively associated with the urinary mesothelin(std) levels (adjusted R(2) = 0.49). Mesothelin levels in urine are affected by impaired glomerular and tubular function, which can influence the interpretation of mesothelin measurements and might cause false-positive results. These effects need to be accounted for to improve the further validation and possible clinical use of urinary mesothelin.


Assessment of aortic stiffness by cardiovascular magnetic resonance following the treatment of severe aortic stenosis by TAVI and surgical AVR.
Aortic stiffness is increasingly used as an independent predictor of adverse cardiovascular outcomes. We sought to compare the impact of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) upon aortic vascular function using cardiovascular magnetic resonance (CMR) measurements of aortic distensibility and pulse wave velocity (PWV). A 1.5 T CMR scan was performed pre-operatively and at 6 m post-intervention in 72 patients (32 TAVI, 40 SAVR; age 76 ± 8 years) with high-risk symptomatic severe aortic stenosis. Distensibility of the ascending and descending thoracic aorta and aortic pulse wave velocity were determined at both time points. TAVI and SAVR patients were comparable for gender, blood pressure and left ventricular ejection fraction. The TAVI group were older (81 ± 6.3 vs. 72.8 ± 7.0 years, p < 0.05) with a higher EuroSCORE II (5.7 ± 5.6 vs. 1.5 ± 1.0 %, p < 0.05). At 6 m, SAVR was associated with a significant decrease in distensibility of the ascending aorta (1.95 ± 1.15 vs. 1.57 ± 0.68 × 10(-3)mmHg(-1), p = 0.044) and of the descending thoracic aorta (3.05 ± 1.12 vs. 2.66 ± 1.00 × 10(-3)mmHg(-1), p = 0.018), with a significant increase in PWV (6.38 ± 4.47 vs. 11.01 ± 5.75 ms(-1), p = 0.001). Following TAVI, there was no change in distensibility of the ascending aorta (1.96 ± 1.51 vs. 1.72 ± 0.78 × 10(-3)mmHg(-1), p = 0.380), descending thoracic aorta (2.69 ± 1.79 vs. 2.21 ± 0.79 × 10(-3)mmHg(-1), p = 0.181) nor in PWV (8.69 ± 6.76 vs. 10.23 ± 7.88 ms(-1), p = 0.301) at 6 m. Treatment of symptomatic severe aortic stenosis by SAVR but not TAVI was associated with an increase in aortic stiffness at 6 months. Future work should focus on the prognostic implication of these findings to determine whether improved patient selection and outcomes can be achieved.


The spread of Hydramoeba infections in mixed hydra species systems.
The host-pathogen system, hydra and Hydramoeba hydroxena, was used as an experimental analog to explore properties of epizootics in mixed host species systems, and to determine the contribution of each host species to a measure of overall host community resistance. Epizootics of hydramoeba in systems of two host species were characterized by processes of enhancement and buffering of the infection where one host species is more resistant than the other. More complex host communities were constructed from four hydra species by varying the proportions of each. Community size and number of species were kept constant. Instantaneous infection rates and time infection reached a specific level were judged measures of community resistance or resilience. A Community Resistance Index(R c ) was devised that associated an independent measure of the resistance of each component species in the system with the corresponding abundance of the species in the system. Experimental results indicated significant differences in infection rates and infection level time among the synthetic communities. R c was found predictive of the behavior of the systems under pathogen stress and was considered a realistic measure of community resistance to stress. First order host species interactions were present during the infection process and lead to more complex enhancement processes involving transfer and accumulation of pathogen material. These interactions, however, were not of sufficient magnitude to render the positive R c -community resistance regression insignificant.


Progesterone treatment alters neurotrophin/proneurotrophin balance and receptor expression in rats with traumatic brain injury.
The neuroactive steroid progesterone (PROG) has been shown to be an effective treatment for traumatic brain injury (TBI) both in animal models and in humans, but the signaling pathways involved have not yet been fully described. Here we characterize the protein expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and their pro-proteins and receptors following PROG treatment for TBI. To evaluate whether PROG treatment given after TBI alters mature and proneurotrophin protein balance and the expression of receptors involved in apoptotic and cell survival signaling, we used Western blots in tissue obtained 24 h, 72 h, and 7 days after injury from rats with bilateral frontal cortical contusions. Compared to controls, PROG reduced levels of pro-apoptotic NGF precursor (proNGF) at 24 h and 7 days post-injury, reduced levels of pro-apoptotic BDNF precursor (proBDNF) and the BDNF receptor TrkB at all time points, and increased levels of mature NGF at 72 h. Levels of mature BDNF were decreased at 24 and 72 h. These observations were associated with reduced markers of apoptosis and improved behavioral parameters in PROG-treated rats. Some of PROG's protective effects after TBI are mediated, in part, by simultaneous induction of pro-survival neurotrophin signaling and inhibition of apoptotic proneurotrophin signaling.


Durability of antireflux effect of ureteral reimplantation for primary vesicoureteral reflux: findings on long-term cystography.
To evaluate the long-term durability of successful ureteral reimplantation (UR) for vesicoureteral reflux (VUR) through a review of late cystography (LC) findings. We performed a retrospective chart review of all children with primary VUR who underwent successful open UR (grade 0 VUR into the reimplanted ureter[s] on initial cystogram) at our institution from January 1990 to December 2002. We identified successful UR patients who underwent LC ≥ 1 year after UR and reviewed the results for the presence of recurrent VUR into the reimplanted ureter(s). Seven-hundred ninety-four patients underwent successful open UR for primary VUR, of whom 60 (7.6%) had a subsequent LC. Preoperative VUR grade was ≤ II in 20 (34.5%) and ≥ III in 38 (65.5%). Median age at UR was 3.5 years (IQR 1.3-6.2 years); 51 (85%) were female. UR was intravesical in 45 (75%) and bilateral in 19 (32%). LC was performed at a median of 38.7 months after UR (IQR 19.6-66.1 months). Indication for LC was febrile urinary tract infection (UTI) in 16 (27%), nonfebrile UTIs in 15 (25%), follow-up of contralateral VUR in 16 (27%), and other clinical indications in 13 (21%). The recurrence rate was 0%; of the 79 reimplanted ureters, 100% (95% CI 95.4-100) had no VUR (grade 0). Among children who underwent successful open UR for primary VUR, there was no VUR recurrence on extended follow-up. This suggests that the late durability of open antireflux surgery is excellent.


Efficacy of flecainide in the management of ventricular arrhythmias: comparative study with amiodarone.
The effects on ventricular arrhythmias of a new class IA drug, flecainide, were compared with those of amiodarone in 10 patients with frequent, chronic, and stable ventricular ectopic beats (VEBs). The study consisted of an initial 1-week, placebo-controlled, baseline period followed by two 12-day, randomized, crossover, double-blind treatment periods with incremental dosage and 1 month of placebo between drug periods. Frequent VEBs, which were present in all 10 patients during both placebo control periods (30 or more VEBs/hour every hour, during 24-hour Holter monitoring), were markedly suppressed (reduction greater than 80%) in nine patients with both drugs (p less than 0.01). There was almost total abolition of the VEBs in six patients with flecainide, and the satisfactory results with a minimal dose in three demonstrate its fast onset of action. Side effects from either agent were infrequent and no discontinuation was necessary. We conclude from our study that flecainide is a highly effective antiarrhythmic agent.


The regulation of ApoB metabolism by insulin.
The leading cause of death in diabetic patients is cardiovascular disease. Apolipoprotein B (ApoB)-containing lipoprotein particles, which are secreted and cleared by the liver, are essential for the development of atherosclerosis. Insulin plays a key role in the regulation of ApoB. Insulin decreases ApoB secretion by promoting ApoB degradation in the hepatocyte. In parallel, insulin promotes clearance of circulating ApoB particles by the liver via the low-density lipoprotein receptor (LDLR), LDLR-related protein 1 (LRP1), and heparan sulfate proteoglycans (HSPGs). Consequently, the insulin-resistant state of type 2 diabetes (T2D) is associated with increased secretion and decreased clearance of ApoB. Here, we review the mechanisms by which insulin controls the secretion and uptake of ApoB in normal and diabetic livers.


Meta-analysis of effects of age on intestinal digestibility of liquid feeds in young calves.
A meta-analysis was conducted to determine the effect of age on digestibility of liquid feeds fed to preweaned Holstein calves. Calves were 4 to 76 d of age and fed whole milk or milk replacer containing all-milk protein. Least squares means of apparent total-tract N, DM, and fat digestibilities (n = 84, 51, and 24, respectively) from 12 publications were used. Broken line regression and mixed model ANOVA were used to determine ages at which digestion of nutrients no longer increased with age, indicating maturation of digestive capacity. Digestibility of DM, N, and fat reached maximum digestibilities of 94.1, 92.7, and 97.5% at 29, 29, and 32 d of age, respectively. These data indicate age-related changes in digestion of liquid feeds in preweaned Holstein calves and allow correction of apparent total-tract digestibility estimates in nutrient supply models. Digestibility of liquid nutrients in calves fed whole milk or all milk containing milk replacers reached maximal capacity at approximately 30 d of age.


Acidobacteria members harbour an abundant and diverse carbohydrate-active enzymes (cazyme) and secreted proteasome repertoire, key factors for potential efficient biomass degradation.
The Acidobacteria phylum is a very abundant group (20-30% of microbial communities in soil ecosystems); however, little is known about these microorganisms and their ability to degrade the biomass and lignocellulose due to the difficulty of culturing them. We, therefore, bioinformatically studied the content of lignocellulolytic enzymes (total and predicted secreted enzymes) and secreted peptidases in an in silico library containing 41 Acidobacteria genomes. The results showed a high abundance and diversity of total and secreted Carbohydrate-Active enzymes (cazyme) families among the Acidobacteria compared to known previous degraders. Indeed, the relative abundance of cazymes in some genomes represented more than 6% of the gene coding proteins with at least 300 cazymes. The same observation was made with the predicted secreted peptidases with several families of secreted peptidases, which represented at least 1.5% of the gene coding proteins in several genomes. These results allowed us to highlight the lignocellulolytic potential of the Acidobacteria phylum in the degradation of lignocellulosic biomass, which could explain its high abundance in the environment.


Comparative study on the use of anticoagulants heparin and recombinant hirudin in a rabbit traumatic anastomosis model.
Antithrombotic drugs, such as heparin, have been used in the clinics for a long time. Heparin acts by binding with antithrombin III to form a complex thereby enhancing the activity of antithrombin III to inactivate coagulation factors IIa, IXa, Xa, XIa and XIIa. Hirudin is a new antithrombotic agent and is reported to be much more powerful than heparin on a gravimetric basis. When both are administered systemically, one of the common complications seen is bleeding. Some previous studies have shown that local vascular endothelial concentrations of heparin are 30 to 7500 times greater than those found in the circulating blood. In order to avoid such complications, topical administration of antithrombotic drugs may be an ideal route of administration. The rabbit ear arterial crush-avulsion thrombosis model was used in this study. The animals were divided into five groups: one control group and four treatment groups which received varying concentrations of heparin and hirudin. In the saline control group, the patency rate was 19.23% at 24 hrs and 15.38% at 7 days. A higher patency rate at 7 days was obtained in groups treated with high concentration of heparin and hirudin. ACT, PT and APTT performed on samples drawn one hour after drug administration were within the normal range in both the control and the treatment groups. Scanning electron microscopy revealed the different extent of the clots on the injured intimal surfaces of the vessels in different groups. The results indicate that high concentrations of topically administered heparin or hirudin minimize the systemic complications and maximize the antithrombotic effects.


Isolation of Nucleoid Fraction from Mycoplasma gallisepticum Cells with Synchronized Cell Division.
It is assumed that unknown mechanisms can be involved in adaptation Mycoplasma gallisepticum to unfavorable factors, one of these can be local rearrangements of the structure and spatial organization of the chromosome. To study these mechanisms, we obtained a culture of M. gallisepticum with synchronized division and isolated the nucleoid fraction from this culture by the method of mild cell lysis and centrifugation in a sucrose gradient. Liquid chromatography-mass spectrometry analysis of the proteome showed that in comparison with the cell lysate, the nucleoid fraction was enriched with DNA-binding proteins. This analysis will help to find new nucleoid-associated proteins and to study their dynamics, distribution, and their role during infection and under stress conditions.


Anal and perianal abnormalities in prepubertal victims of sexual abuse.
We describe anal and perianal findings in 310 prepubertal children who were determined to be victims of sexual abuse; 206 (66%) had perinea that appeared normal. Abnormal findings were present in 104 children (34%): anal gapping in 61 children; skin tags in 44; rectal tears in 33; sphincter tears in 15; human papillomavirus lesions in 4; perineal scarring in 2; and bite marks in 1. Normal-appearing perianal and anal regions were noted in 150 of 175 children (85%) who denied anal assault, and in 11 of 70 (16%) who described such assault. In comparison, anal and perianal abnormalities were observed in 59 of the 70 children (84%) who gave a clear history of anal assault, but in only 25 of 175 (15%) who denied such abuse. Failure to document perianal abnormalities in almost two thirds of the patients demonstrates the limitations of the medical evaluation in validating allegations of sexual abuse.


A pituitary-salivary mixed gland induced by tissue recombination of embryonic pituitary epithelium and embryonic submandibular gland mesenchyme in mice.
Renal subcapsular syngrafts of Day 9 to 11 mouse embryonic pituitary epithelium with Day 14 mouse embryonic submandibular gland mesenchyme produced mixed organs that include residual cleft structure surrounded by anterior pituitary cells some which are stained by anti-ACTH antiserum and submandibular gland-like structure with differentiated acinar cells which are stained by anti-alpha-amylase antiserum. However, when Day 8.5 or 12 embryonic pituitary epithelium was recombined with submandibular gland mesenchyme and syngrafted, development of submandibular gland-like or anterior pituitary tissues resulted, respectively. Thus, during organogenesis of the mouse anterior pituitary, there exists a developmental stage (Day 8.5-11 in utero), when prospective pituitary epithelium can respond to heterotypic submandibular gland mesenchyme with the development of a submandibular gland-like tissue.


Regulation of volume-sensitive Cl- channels in multi-drug resistant MCF7 cells.
The P-glycoprotein (P-gp) is thought to be involved in the regulation of volume-sensitive chloride channels. In this study, the possible coupling between P-gp and swelling-activated chloride channels has been examined in MCF7 cells with sensitive (MDR-), resistant (MDR+), and reversed resistant (MDR(REV)) phenotypes. Western blot analysis showed that incubation of cells with doxorubicin induced P-gp expression in a reversible manner. Exposure of MDR+ cells to hypotonicity resulted in an inhibition of P-gp activity while hypotonic challenges induced swelling-activated chloride currents (I(Cl-swell)) in MDR-, MDR+, and MDR(REV) MCF7 cells. While verapamil inhibited I(Cl-swell) in all cell types, doxorubicin and vincristine rapidly and reversibly inhibited I(Cl-swell) uniquely in MDR+. Intracellular dialysis of MDR+ cells with C219 anti-P-gp antibody abolished the sensitivity of I(Cl-swell) to doxorubicin and led to a response pattern very close to that of MDR- cells. Taken together, these results strongly suggest that the P-glycoprotein regulates I(Cl-swell) in resistant MCF7.


Functional preservation of the mammalian kidney. VI. Viability assessment of rabbit kidneys perfused at 25 degrees C with dimethyl sulfoxide in RPS-2.
The study utilizes an ex vivo perfusion model to evaluate the effects of warm perfusion (25 degrees C) with two K+-rich vehicle solutions (RPS-2 and solution A) on whole rabbit kidneys. The suitability of the solutions as vehicles for introducing cryoprotectant concentrations (2.8 and 3.5 M) of dimethyl sulfoxide (Me2SO) and the effects of the addition of albumin to RPS-2 are also tested. Albumin (5 g/dl) does not appreciably improve the renal perfusion dynamics of RPS-2. Results indicate that both RPS-2 and solution A serve as effective vehicles for the introduction of 2.8 M Me2SO, and the continued investigation of the RPS-2/Me2SO protocol is advocated.


Tailored Catalytic Nanoframes from Metal-Organic Frameworks by Anisotropic Surface Modification and Etching for the Hydrogen Evolution Reaction.
A facile anisotropic surface modification and etching strategy is presented for the synthesis of hollow structured ZIF-67 nanoframes. The strategy uses structural and compositional distinctions between each crystallographic facet of truncated rhombic dodecahedrons ZIF-67 (tZIF-67 RDs) and the moderate coordinating and etching effects of cyanuric acid (CA). The CA can anisotropically modify and protect the {110} facets from etching, causing the six {100} facets be selectively etched via an inside-out manner, and finally forming the hollow nanoframes. The surface-modified hollow tZIF-67 RDs can be facet-selectively etched by metal salts in an outside-in manner to give metal-doped tZIF-67 nanoframes. After calcination, the metal-tZIF-67 hybrids are converted into metal-Co alloy/C composite catalysts with hollow nanoframed structures. The PtCo/C catalyst with only 5.9 wt % Pt exhibits high catalytic activities and stabilities in the hydrogen evolution reaction (HER) in acidic solutions.


[Functional analysis of the single nucleotide polymorphisms in the PRKCZ gene].
To study the function of 5 single nucleotide polymorphisms (SNPs) of the PRKCZ gene, a susceptibility gene for type 2 diabetes in Han population of North China, in the pathogenesis of the disease. Bioinformatic methods and reporter gene activity determination were used to analyze the function of the 5 SNPs. The reporter gene activities of different alleles of 2 SNPs, rs427811 and rs809912, were obviously different, which implies that these 2 SNPs might be susceptibility loci of the disease. The PRKCZ gene is further confirmed to be a susceptibility gene for type 2 diabetes in Han population of North China. Two SNPs in the gene play a role in the pathogenesis of the disease by affecting the expression level of PRKCZ gene.


The production of creatine kinase isozyme BB in sera of a patient with prostatic carcinoma and in tumor homogenates.
1. A CK(BB) fraction was observed in sera of a patient with prostatic carcinoma. The fraction accounted for 59% of the total enzyme activity. A metastatic tumor of a prostatic carcinoma was observed to contain solely the CK(BB) isozyme. An embryonal testicular carcinoma was observed to have a higher percentage of the CK(BB) fraction when compared to the adjacent tumor free testicular tissue in a third patient. These studies suggested that in certain carcinomas there are tissue isozyme modifications at the molecular level. The isozymic modification was suggested as a reversion towards an embroyonic pattern as the adult molecular form tended to disappear while the fetal form increased. This too suggests that the isozymes of CK may be a useful model in elucidating the mechanism through which this transition occurs. 2. The high percentage of CK(BB) in the sera of the patient with metastasis was discussed. The origin could not be determined, but either a primary tumor or a metastatic tumor by their enzyme modifications could account for this increased fraction in sera.


A solvent sensitive coumarin derivative coupled with gold nanoparticles as selective fluorescent sensor for Pb2+ ions in real samples.
A coumarin based fluorescent molecule, 3-amino-2-cynano-3-(7-diethylamino-2-oxo-2H-chromen-3-yl)-acrylic acid ethyl ester (1) has been synthesized and characterised. Photophysical studies of 1 exhibit polarity dependent shift of its emission maxima which have been explained on the basis the existence of polar excited state of the molecule. Combination of compound 1 and citrate capped AuNPs (AuNPs/1 conjugate) has been used as a sensing tool for heavy metals. AuNPs/1 conjugate has been found to detect Pb2+ selectively by naked-eye color change as well as fluorescence enhancement. On addition of molecule 1 to gold nanoparticles solution, the color of the solution becomes reddish followed by quenching in fluorescence intensity. With gradual addition of Pb2+, the solution of AuNPs/1 conjugate becomes violet accompanied by a fluorescence enhancement. Excited state lifetime measurement revealed that compound 1 exhibits very fast decay pattern in aqueous medium whereas in AuNPs medium the lifetime of 1 increases. Upon addition of Pb2+ ions to that AuNPs/1 solution the lifetime of 1 decreases again. Based on the experimental observations the mechanism of sensing of lead has been proposed thoroughly. Initially compound 1 gets absorbed on the surface of the spherical gold nanoparticles. When Pb2+ is added, probably gold nanoparticles aggregates to form bigger particles by releasing compound 1 from its surface to show fluorescence enhancement.


Comparison of the once-daily levofloxacin-containing triple therapy with the twice-daily standard triple therapy for first-line Helicobacter pylori eradication: a prospective randomised study.
Simple compound of Helicobacter pylori eradication therapy may improve drug compliance of patients. The aims of this study were to compare the efficacy and tolerability of a simple combination containing levofloxacin 7-day once-daily with standard twice-daily triple therapy. This was a prospective, randomised, open-label trial. A total of 189 consecutive patients diagnosed with peptic ulcer and H. pylori infection were enrolled. Patients were randomly divided into two groups: LEC group--levofloxacin 500 mg, esomeprazole 40 mg and clarithromycin 500 mg once daily for 7 days; AEC group--amoxicillin 1 g, esomeprazole 40 mg and clarithromycin 500 mg twice daily for 7 days. There were 90 patients in the LEC group and 99 patients in the AEC group. By intention-to-treat and per-protocol analysis, the H. pylori eradication rate was 78.9% [71/90; 95% confidence interval (CI), 70.3-87.5%] and 83.5% (71/85; 95% CI, 75.5-91.6%) respectively, in the LEC group; and 74.8% (74/99; 95% CI, 66.0-83.5%) and 86.0% (74/86; 95% CI, 78.6-93.5%) respectively, in the AEC group. The incidence and tolerability of side effects were similar between these two groups. The efficacy and tolerability of once-daily levofloxacin-containing triple therapy are equal to those of the standard twice-daily triple therapy in this study. However, none of the treatment regimens evaluated achieved enough eradication efficacies to be considered as a recommendable first-line treatment.


Brainstem reticular stimulation facilitates back muscle motoneuronal responses to pudendal nerve input.
In urethane or pentobarbital anesthetized female rats, stimulation with bipolar electrodes in the medullary reticular formation evoked activity in lateral longissimus muscle nerves, when trains of pulses were applied. Combined stimulation of the medullary reticular formation and the pudendal nerve revealed a marked mutual facilitation of their two separate effects on the excitability of the lateral longissimus muscle nerves. These results match previous conclusions based on the effects of spinal column transection on the pudendal nerve-evoked response, and are consistent with a role for this mutual facilitation in the control of lordosis behavior.


Novel multi-marker proteomics in phenotypically matched patients with ST-segment myocardial infarction: association with clinical outcomes.
Early prediction of significant morbidity or mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) represents an unmet clinical need. In phenotypically matched population of 139 STEMI patients (72 cases, 67 controls) treated with primary percutaneous coronary intervention, we explored associations between a 24-h relative change from baseline in the concentration of 91 novel biomarkers and the composite outcome of death, heart failure, or shock within 90 days. Additionally, we used random forest models to predict the 90-day outcomes. After adjustment for false discovery rate, the 90-day composite was significantly associated with concentration changes in 14 biomarkers involved in various pathophysiologic processes including: myocardial fibrosis/remodeling (collagen alpha-1, cathepsin Z, metalloproteinase inhibitor 4, protein tyrosine phosphatase subunits), inflammation, angiogenesis and signaling (interleukin 1 and 2 subunits, growth differentiation factor 15, galectin 4, trefoil factor 3), bone/mineral metabolism (osteoprotegerin, matrix extracellular phosphoglycoprotein and tartrate-resistant acid phosphatase), thrombosis (tissue factor pathway inhibitor) and cholesterol metabolism (LDL-receptor). Random forest models suggested an independent association when inflammatory markers are included in models predicting the outcomes within 90 days. Substantial heterogeneity is apparent in the early proteomic responses among patients with acutely reperfused STEMI patients who develop death, heart failure or shock within 90 days. These findings suggest the need to consider synergistic multi-biomarker strategies for risk stratification and to inform future development of novel post-myocardial infarction therapies.


Leishmania infection in rodents in Greece.
To investigate the prevalence of Leishmania infection in rodents from various areas of northern Greece. Ninety-seven rodents (66 Mus musculus, 19 Rattus norvegicus and 12 R. rattus) were collected during pest control programmes and examined by cytology (spleen and liver smears), serology (ELISA) and PCR (real-time and gel-based) for Leishmania. Date, environment, sex, existence of dogs in the close environment were recorded for each rodent. All cytological preparations were negative, whereas specific IgG was detected in 54.5% in total; 70% of R. norvegicus; 50% of R. rattus; and 50% of M. musculus. In at least one molecular method, 19.6% of the samples in total were positive: 25% of R. rattus, 24% of M. musculus, but no R. norvegicus was found positive. Environment (semi-urban areas, P = 0.037) and species (M. musculus, P = 0.032) were associated with positive PCR. All infected animals showed evidence of low parasite burden, demonstrated by the negative cytological examinations and the high Ct values observed in real-time PCR. Due to the proximity of rodents to humans and dogs, these animals may be important in the epidemiology of leishmaniosis, especially if proven that they can infect sand flies.


Carbon dioxide fixation and lipid storage by Scenedesmus obtusiusculus.
An indigenous microalga was isolated from the springs in Cuatro Ciénegas, México. It was morphologically identified as Scenedesmus obtusiusculus and cultivated in bubble-column photobioreactors in batch operation mode. This microalga grows at 10% of carbon dioxide (CO(2)) showing a maximum CO(2) fixation rate of 970gm(-3)d(-1). The microalga, without any nutrient limitation, contained 20% of nonpolar lipids with a biomass productivity of 500gm(-3)d(-1) and a maximum biomass concentration of around 6,000gm(-3) at 5% CO(2) and irradiance of 134μmolm(-2)s(-1). Furthermore, it was observed that the microalga stored 55.7% of nonpolar lipids when 5% CO(2) was fed at 0.8vvm and 54.7μmolm(-2)s(-1) under nitrogen starvation. The lipid profile included C16:0, C18:0, C18:1n9t, C18:1n9c, C18:3n6 with a productivity of 200g lipid m(-3)d(-1). Therefore, the microalga may have biotechnological potential producing lipids for biodiesel.


Viral load as a surrogate end point in HIV disease.
To examine the role of viral load as a surrogate end point for HIV disease progression and death. A MEDLINE search was conducted for the years 1990-March 2001. In addition, relevant articles were cross-referenced to screen for additional information. Data regarding the validity of viral load as a surrogate end point for disease progression or death are cited. Emphasis was placed on randomized, controlled trials, but descriptive studies are also included. Recently, viral load has emerged as an important biomarker for monitoring HIV disease and antiretroviral therapy. Both baseline viral load and changes in viral load with time predict HIV disease progression and death. In fact, disease progression increases consistently once viral load exceeds 10,000 copies/mL, and AIDS and death primarily occur in patients with viral loads > 100,000 copies/mL. Changes that occur in viral load after initiation of antiretroviral therapy, however, do not fully explain the entire treatment effect. Also, separate comparisons of antiretroviral regimens may demonstrate similar differences in viral load changes but not similar differences in disease progression. Viral load is an important monitoring parameter for HIV disease and antiretroviral therapy. However, changes in viral load do not explain the entire clinical improvement that occurs after initiation of therapy. Although viral load is a clinically important surrogate end point for HIV disease, it cannot fully account for all associated treatment effects.


Immunological evidence for the association between simian virus 40 115-kDa super T antigen and hsp70 proteins in rat, monkey, and human cells.
Immunological evidence was provided that in subclone 7 cell line, which is derived from SV40 transformed cells, 115-kDa super T antigen, a transformation-competent, elongated form of large T antigen was physically complexed with hsp70 proteins. This conclusion was first based on the coimmunoprecipitation from unstressed or heat shocked subclone 7 cells of both super T antigen and hsp70 proteins. This was observed with any one of a set of anti-T monoclonal antibodies reacting to determinants located either in the C-terminal region or in the N terminal region. Reciprocally coimmunoprecipitation of both hsp70 and super T was also observed in the anti-hsp70 peptide serum-immunoprecipitate. The formation of complexes between hsp70 proteins and super T antigen in subclone 7 cells was also confirmed by Western blot experiments. Moreover, when expressed in cell lines originating from human (Hela cells) or monkey (CV1P cells) species following transfection with the relevant plasmid, super T antigen again displayed the ability to associate with hsp70 proteins. Considering that super T antigen was obtained in laboratory experiments as a stable evolutionary variant of SV40 large T antigen, it is suggested that the marked ability of super T antigen to associate with heat shock protein could be selectively advantageous under certain conditions.


Localized vulvar pemphigoid in a child.
Bullous pemphigoid often affects the elderly but is not common in children. At least two localized variants, cicatricial pemphigoid and localized, chronic pemphigoid of Brunsting-Perry, have been described. A case of bullous pemphigoid in a 9-year-old girl was unusual because erosions were limited to the vulvar area. Other bullous dermatoses were considered in the differential diagnosis. Histopathologic examination and immunofluorescence microscopic studies, as well as immunoelectron microscopic studies, which yielded unique results, were performed to confirm the diagnosis.


Troponin as a predictor of outcomes in transcatheter aortic valve implantation: systematic review and meta-analysis.
Transcatheter aortic valve implantation (TAVI) is emerging as a therapeutic gold standard in the management of aortic stenosis. However, post-procedural complications of this procedure are being increasingly recognised. We therefore performed this systematic review and meta-analysis on the prognostic value of elevated troponin prior to TAVI to predict risk of post-procedural complications. We searched Medline (Ovid), Embase (Ovid), and the Cochrane Library from inception until May 2022, and included studies on the association between elevated pre-procedural troponin with 30-day mortality, long-term mortality, and post-procedural myocardial injury (PPMI). We generated summary odds ratios (OR) and hazards ratios (HR) using random-effects meta-analysis and performed subgroup analyses to evaluate differences in troponin threshold selection. Inter-study heterogeneity was tested using the I2 test. We included 10 studies involving 4200 patients. Serum troponin elevation prior to TAVI was significantly associated with long-term mortality [HR = 2.09 (95% CI 1.30-3.36)], but not with 30-day mortality [OR 1.76 (95% CI 0.96-3.22)]. Subgroup analysis showed a trend towards increased effect size and statistical significance for 30-day mortality as troponin elevation was more narrowly defined. Two studies reported on PPMI and found no statistically significant mean difference between groups. Raised serum troponin is associated with increased long-term mortality following TAVI. Further clarification on the optimal troponin threshold for risk identification is required. High-quality studies that utilise ROC analysis for threshold selection are warranted.


Taming chlorophylls by early eukaryotes underpinned algal interactions and the diversification of the eukaryotes on the oxygenated Earth.
Extant eukaryote ecology is primarily sustained by oxygenic photosynthesis, in which chlorophylls play essential roles. The exceptional photosensitivity of chlorophylls allows them to harvest solar energy for photosynthesis, but on the other hand, they also generate cytotoxic reactive oxygen species. A risk of such phototoxicity of the chlorophyll must become particularly prominent upon dynamic cellular interactions that potentially disrupt the mechanisms that are designed to quench photoexcited chlorophylls in the phototrophic cells. Extensive examination of a wide variety of phagotrophic, parasitic, and phototrophic microeukaryotes demonstrates that a catabolic process that converts chlorophylls into nonphotosensitive 132,173-cyclopheophorbide enols (CPEs) is phylogenetically ubiquitous among extant eukaryotes. The accumulation of CPEs is identified in phagotrophic algivores belonging to virtually all major eukaryotic assemblages with the exception of Archaeplastida, in which no algivorous species have been reported. In addition, accumulation of CPEs is revealed to be common among phototrophic microeukaryotes (i.e., microalgae) along with dismantling of their secondary chloroplasts. Thus, we infer that CPE-accumulating chlorophyll catabolism (CACC) primarily evolved among algivorous microeukaryotes to detoxify chlorophylls in an early stage of their evolution. Subsequently, it also underpinned photosynthetic endosymbiosis by securing close interactions with photosynthetic machinery containing abundant chlorophylls, which led to the acquisition of secondary chloroplasts. Our results strongly suggest that CACC, which allowed the consumption of oxygenic primary producers, ultimately permitted the successful radiation of the eukaryotes throughout and after the late Proterozoic global oxygenation.


Low-molecular-weight heparin may alter point-of-care assay for international normalized ratio.
To compare the international normalized ratio (INR) measured by a point-of-care testing device with that measured by a reference laboratory method for patients receiving either warfarin only or warfarin plus low-molecular-weight heparin (LMWH). Retrospective study. Outpatient anticoagulation clinic. Ninety-one patients receiving warfarin for various indications; 59 of them receiving only warfarin and 32 receiving warfarin plus LMWH. Capillary blood was obtained for INR determination by a point-of-care device, and venous blood was obtained for INR determination in a standard reference laboratory. Ninety-one patients had INR pairs run on a point-of-care device and by the laboratory. In both the patients receiving only warfarin and in those receiving warfarin plus LMWH, the mean INR as determined by the point-of-care testing device was statistically significantly higher than the mean INR determined by the laboratory. Although the differences were statistically significant in both groups, the clinical significance of this difference was accentuated in the patients receiving warfarin plus LMWH. The measure of divergence between the point-of-care and laboratory methods was greater in the group receiving warfarin plus LMWH than in the warfarin-only group, with a mean +/- SD percent change between the INR values of 24.19 +/- 27.54% in the warfarin plus LMWH group and 7.21 +/- 17.73% in the warfarin-only group. In assessing the clinical impact of such variability, a greater degree of discordance in dosing adjustment decisions was noted for patients receiving warfarin plus LMWH. In this group, a 25% rate of discordance was noted compared with 8% in the warfarin-only group. Such discrepancy in dosing decisions based on the point-of-care INR would have resulted in discontinuation of LMWH therapy before the patient acquired a true therapeutic INR, with use of the laboratory measurement. The INR measured with the point-of-care device in patients receiving concurrent LMWH and warfarin therapy may be inaccurate. Patients receiving LMWH in addition to warfarin should have INRs checked by means of the standard reference laboratory method.


The effects of carotid body hypocapnia on ventilation in goats.
This study was designed to examine the influence of carotid body (CB) hypocapnia on ventilation by selectively perfusing the CB through an extracorporeal circuit in 19 goats. When PcbCO2 was decreased from normocapnic levels in 14 awake goats (delta PcbCO2 = 10.9 Torr), PaCO2 increased 5.6 Torr (P less than 0.05) and VE decreased 24% (P less than 0.001) (mean values). The ventilatory sensitivity to inspired CO2 was not changed by CB hypocapnia in 5 of these goats, but the response was shifted to the right. During CB hypocapnia, ventilatory instability, including apnea, was observed in 4 of 14 goats; this irregular breathing continued at elevated levels of PaCO2. In 5 anesthetized goats, CB hypocapnia (delta PcbCO2 = 18.0 Torr) decreased VE by 70% in the intact state, but produced no significant ventilatory depression after CB denervation. We conclude that CB hypocapnia depresses ventilation in both awake and anesthetized goats mostly through CB chemoreceptor effects, and suggest that this hypoventilation may predispose to ventilatory instability in some animals.


Distribution areas and monthly dynamic distribution changes of three Aedes species in China: Aedes aegypti, Aedes albopictus and Aedes vexans.
Mosquitoes play an absolute role in the spread of epidemic arbovirus diseases. Worldwide, Aedes aegypti and Aedes albopictus are the main vectors responsible for the spread of these mosquito-borne diseases. Aedes vexans, a mosquito species native to China, also carries mosquito-borne viruses, such as dengue fever virus and Japanese encephalitis virus, but research on this mosquito has been inadequate. Mapping the potential distribution range of and monthly change in the distribution of these three Aedes species is of particular importance for mosquito surveillance, eradication and disease control. Monitoring data were collected for the three Aedes species in China. Long-term temperature and precipitation data (2001-2021) and land cover data were used to represent various climate and environmental conditions. An ecological niche model was developed using a maximum entropy modeling method to predict the current optimum habitat areas for the three Aedes species and to obtain important variables influencing their monthly distribution. The distribution model for the three Aedes species performed well, with an area under the receiver operating characteristic curve value of 0.991 for Ae. aegypti, 0.928 for Ae. albopictus and 0.940 for Ae. vexans. Analysis of the distribution change and mapping of the optimum habitat range for each Aedes species for each month demonstrated that temperature, precipitation and construction land were important factors influencing the distribution of these three Aedes species. In China, Aedes aegypti is mainly concentrated in a few tropical regions and along the Yunnan border; Aedes albopictus is widely distributed throughout most of the country, except for the arid and semi-arid regions of northwest China; and Aedes vexans is mainly found in the northern regions. Our results provide a basis for the timing and location of surveillance efforts for high-priority mosquitoes.


Development of seam tracking device in asynchronous tandem welding with arc sensing.
Tandem welding is extensively used for welding large structures, such as ships and plants, for increased welding speed and volume. Seam tracking is essential because of a large amount of thermal deformation. However, in tandem welding, arc interference causes current and voltage to vary non-uniformly, leading to difficulties in seam tracking. Therefore, in this study, an optimal signal was identified for seam tracking in tandem welding and evaluated. To select the seam-tracking signal, an algorithm was developed that separates the welding signal into peak, average, and base. Based on the collected data, regression and signal-to-noise ratio analyses were performed to identify a suitable seam-tracking signal. To trace the welding line based on the selected signal, the welding signal was checked by weaving on the V-groove specimen. As a result, the current area difference of the welding signal generated between the left and right parts of the center of the V-groove could be calculated. An algorithm and equipment for seam tracking were constructed using the area difference of the welding current. Finally, the seam tracking system was verified by conducting an actual test using the equipment to which the algorithm was applied.


S. Typhimurium virulence changes caused by exposure to different non-thermal preservation treatments using C. elegans.
The aims of this research study were: (i) to postulate Caenorhabditis elegans (C. elegans) as a useful organism to describe infection by Salmonella enterica serovar Typhimurium (S. Typhimurium), and (ii) to evaluate changes in virulence of S. Typhimurium when subjected repetitively to different antimicrobial treatments. Specifically, cauliflower by-product infusion, High Hydrostatic Pressure (HHP), and Pulsed Electric Fields (PEF). This study was carried out by feeding C. elegans with different microbial populations: E. coli OP50 (optimal conditions), untreated S. Typhimurium, S. Typhimurium treated once and three times with cauliflower by-product infusion, S. Typhimurium treated once and four times with HHP and S. Typhimurium treated once and four times with PEF. Bayesian survival analysis was applied to estimate C. elegans lifespan when fed with the different microbial populations considered. Results showed that C. elegans is a useful organism to describe infection by S. Typhimurium because its lifespan was reduced when it was infected. In addition, the application of antimicrobial treatments repetitively generated different responses: when cauliflower by-product infusion and PEF treatment were applied repetitively the virulence of S. Typhimurium was lower than when the treatment was applied once. In contrast, when HHP treatment was applied repetitively, the virulence of S. Typhimurium was higher than when it was applied once. Nevertheless, in all the populations analyzed treated S. Typhimurium had lower virulence than untreated S. Typhimurium.


RNA base-pairing complexity in living cells visualized by correlated chemical probing.
RNA structure and dynamics are critical to biological function. However, strategies for determining RNA structure in vivo are limited, with established chemical probing and newer duplex detection methods each having deficiencies. Here we convert the common reagent dimethyl sulfate into a useful probe of all 4 RNA nucleotides. Building on this advance, we introduce PAIR-MaP, which uses single-molecule correlated chemical probing to directly detect base-pairing interactions in cells. PAIR-MaP has superior resolution compared to alternative experiments, can resolve multiple sets of pairing interactions for structurally dynamic RNAs, and enables highly accurate structure modeling, including of RNAs containing multiple pseudoknots and extensively bound by proteins. Application of PAIR-MaP to human RNase MRP and 2 bacterial messenger RNA 5' untranslated regions reveals functionally important and complex structures undetected by prior analyses. PAIR-MaP is a powerful, experimentally concise, and broadly applicable strategy for directly visualizing RNA base pairs and dynamics in cells.


Monoclonal antibodies against different antigenic determinants of a protein molecule (human serum albumin) as detected after labeling the antigen with two different markers.
By using FITC- and 125I-labeled human serum albumin (HSA) the reactivity of anti-HSA hybridoma antibodies was compared in solid-phase immunofluorescence assay (SIFA) and radioimmunoassay (SRIA). A considerable number of hybridoma antibodies had been detected which are positive in SIFA but not in SRIA. Since this cannot be explained by a difference in the sensitivity of the assays it seems likely that these monoclonal antibodies detect antigenic determinants which contain tyrosine as an essential part.


The validity and utility of geotaxis in young rodents.
Negative geotaxis, an automatic, reliable, stimulus-bound, orientation and movement directionally against gravitational cues, is often used for behavioral assessments of infant rodents. We summarize historical and contemporary analyses and conclude that negative geotaxis does not exist in infant rats. Infant rodents placed on inclined surfaces (ranging from 15 degrees to 70 degrees in most tests) are posturally unstable and their compensatory responses have been misinterpreted as negative geotaxis. In fact, recent findings suggest that if infant rats display a geotaxis, they show positive geotaxis on shallow angles of inclination (e.g., 4 degrees and 8 degrees ). There may be utility in assessing postures and motoric responses of infant rats on relatively robust angles of inclination, but these are not tests of negative geotaxis.


Comparison of risk assessment tools for cardiovascular diseases: results of an Iranian cohort study.
Several popular cardiovascular risk assessment tools have been developed in Western countries; however, the predictive abilities of these tools have not been evaluated in Middle Eastern countries. The present study aimed to determine the abilities of cardiovascular risk assessment tools in a population-based study in Northern Iran. Population-based cohort study in Northern Iran. In total, 2883 individuals (1629 men and 1254 women), aged 40-74 years, were included in the study. We determined the predictive abilities of the American College of Cardiology/American Heart Association (ACC/AHA) risk prediction tool, the Framingham general cardiovascular risk profile in primary care settings, and the Systematic Coronary Risk Evaluation (SCORE) equations for low- and high-risk European countries. Receiver operating characteristic (ROC) analysis was used to determine the predictive abilities of these four risk assessment tools. Based on areas under curve (AUC) values and related 95% confidence intervals (95% CIs), the discriminative abilities of the ACC/AHA tool, the Framingham approach, and the SCORE for low- and high-risk European countries to estimate non-fatal cardiovascular disease (CVD) events were 0.6625, 0.6517, 0.6476 and 0.6458, respectively, in men, and 0.7722, 0.7525, 0.7330 and 0.7331, respectively, in women. Moreover, the abilities of these four tools to estimate fatal CVD events were found to be 0.8614, 0.8329, 0.7996 and 0.7988 in men, and 0.8779, 0.8372, 0.8535 and 0.8518 in women, respectively. The cardiovascular risk assessment tools investigated in this study showed acceptable predictive abilities in women. The ACC/AHA approach showed slightly better performance compared with the SCORE tool; however, the SCORE tool benefited from the lowest cost compared with all the other tools.


DEFINING SECLUSION AND RESTRAINT: LEGAL AND POLICY DEFINITIONS VERSUS CONSUMER AND CARER PERSPECTIVES.
The practices of seclusion and restraint may be used in a variety of health settings to control behaviour. Laws and policies that seek to regulate these practices define seclusion and restraint in various ways and there are gaps as to which practices are regulated and in what circumstances. This column provides an overview of consumer and carer perspectives as to what is meant by these practices.


Manipulation of temperature and illumination conditions for enhanced beta-carotene production by mutant 32 of Rhodotorula glutinis.
Enhancement in the production of beta-carotene by the hyper producer mutant 32 of Rhodotorula glutinis by manipulation of temperature and illumination. Growth and beta-carotene production was investigated in a 1 litre fermenter at different temperature and illumination conditions. The optimum temperature for growth and beta-carotene production was 30 and 20 degrees C, respectively. At 30 degrees C, beta-carotene production was 125 +/- 2 mg l-1 and accounted for 66% of the total carotenoids in 72 h; at 20 degrees C, it was 250 +/- 7 mg l-1 and accounted for 92% of total carotenoid content. Continuous illumination of the fermenter by 1000 lx white light hampered growth as well as carotenoid synthesis. At 30 degrees C, illuminating the fermenter in late logarithmic phase resulted in a 58% increase in beta-carotene production with a concurrent decrease in torulene; at 20 degrees C, however, it showed no appreciable increase. Proper manipulation of culture conditions enhanced beta-carotene production by R. glutinis which makes it a significant source of beta-carotene.


Photoprotective Capabilities of Light-Harvesting Complex II Trimers in the Green Alga Chlamydomonas reinhardtii.
Major light-harvesting complex (LHCII) trimers in plants induce the thermal dissipation of absorbed excitation energy against photooxidative damage under excess light conditions. LHCII trimers in green algae have been thought to be incapable of energy dissipation without additional quencher proteins, although LHCIIs in plants and green algae are homologous. In this study, we investigated the energy-dissipative capabilities of four distinct types of LHCII trimers isolated from the model green alga Chlamydomonas reinhardtii using spectroscopic analysis. Our results revealed that the LHCII trimers possessing LHCII type II (LHCBM5) and LHCII type IV (LHCBM1) had efficient energy-dissipative capabilities, whereas LHCII type I (LHCBM3/4/6/8/9) and type III (LHCBM2/7) did not. On the basis of the amino acid sequences of LHCBM5 and LHCBM1 compared with the other LHCBMs, we propose that positively charged extra N-terminal amino acid residues mediate the interactions between LHCII trimers to form energy-dissipative states.


Environment friendly emerging techniques for the treatment of waste biomass: a focus on microwave and ultrasonication processes.
In the recent past, an increasing interest is mostly observed in using microwave and ultrasonic irradiation to aid the biological conversion of waste materials into value-added products. This study is focused on various individual impacts of microwaves and ultrasonic waves for the treatment of biomass before the synthesis of value-added products. Following, a comprehensive review of the mechanisms governing microwaves and ultrasonication as the treatment methods, their effects on biomass disruption, solubilization of organic matter, modification of the crystalline structure, enzymatic hydrolysis and production of reducing sugars was performed. However, based on the lab-scale experiments evaluated, microwaves and ultrasonication were studied to be economically and energetically ineffective despite their beneficial effects on the waste biomass. This article reviews some of the difficulties associated with using microwaves and ultrasonic irradiation for the efficient processing of waste biomasses and identified some potential directions for future study.


Sprint and endurance training in relation to redox balance, inflammatory status and biomarkers of aging in master athletes.
Studies have shown a positive influence of intense athletic training on several biomarkers of aging, but it remains unclear whether this influence is dependent of exercise-training-mode. This study compared redox balance, cytokine levels and biomarkers of aging between master sprinters and endurance athletes, as well as in young and middle-aged individuals as controls. Participants were male master sprinters (SA, 50 ± 8.9yrs; n = 13) and endurance runners (EA, 53 ± 8.2yrs; n = 18) with remarkable athletic experience (~25yrs of practice), besides untrained young (YC, 22.7 ± 3.9yrs; n = 17) and age-matched controls (MC, 45.5 ± 9.8yrs; n = 12). Anamnesis, anthropometrics, biomarkers of aging, inflammation status and oxidative stress parameters were analyzed in all participants. An increased pro-oxidant activity (elevated protein carbonyl; isoprostanes and 8-OHdG) was observed for MC in comparison to remaining groups (p < 0.05). However, SA presented a better antioxidant capacity than both MC and EA, while nitrite/nitrate (NOx) availability was higher for EA and lower for the MC (p < 0.05). Both groups of athletes presented a better anti-inflammatory status than MC (increased IL-10 and lowered IL-6, sIL-6R, sTNF-RI), but worse than YC (increased TNF-α, sTNF-RI, and sIL-6R) (p < 0.05). Telomere length was shorter in MC, which also had lower levels of irisin and klotho, and elevated FGF-23 (p < 0.05). ADMA levels were higher in MC and SA, while irisin was lower in EA when compared to SA and YC (p < 0.05). Master athletes presented better redox balance and inflammatory status, with decreased biomarkers of aging compared to control. Regarding exercise mode, a better NO- profile, as a marker of endothelial function, was observed for EA, whereas SA had a better redox balance, cytokines profile and attenuated biomarkers of aging.


[Attentive problem in the clinic about acute obstructive anuria at upper urinary tract].
To improve the understanding of acute obstructive anuria at upper urinary tract in order to cope properly with corresponding clinical problems. The clinical problems of acute obstructive anuria at upper urinary tract in 55 patients was summarized and analysed. Anuria, lumbago, edema and progressive increase of blood creatinine and ureal nitrogen were the main bases of diagnosis. B-typed ultrasonography and plain film of abdomen (KUB) were the first choice in examinations. The treatment principles lied in prompt removal of obstruction as well as effective prevention and treatment of infection to protect renal function to maximum extent. Forty-three cases (78.2%) recovered normal renal function. Ten cases (18.2%) still had azotemia three months after treatment. Two cases gave up treatment. The reason of tumor for anuria should be paid attention to. The first choice in treatments is ureteral intubation by cystoscope. Diuretic should be used cautiously.


Randomized clinical trial of early versus delayed temporary stoma closure after proctectomy.
Temporary faecal diversion is recommended with a low colorectal, coloanal or ileoanal anastomosis (LA). This randomized study evaluated early (EC; 8 days) versus late (LC; 2 months) closure of the temporary stoma. Patients undergoing rectal resection with LA were eligible to participate. If there was no radiological sign of anastomotic leakage after 7 days, patients were randomized to EC or LC. The primary endpoints were postoperative morbidity and mortality 90 days after the initial resection. Some 186 patients were analysed. There were no deaths within 90 days and overall morbidity rates were similar in the EC and LC groups (31 versus 38 per cent respectively; P = 0.254). Overall surgical complication (both 15 per cent; P = 1.000) and reoperation (both 8 per cent; P = 1.000) rates were similar, but wound complications were more frequent after EC (19 versus 5 per cent; P = 0.007). Small bowel obstruction (3 versus 16 per cent; P = 0.002) and medical complications (5 versus 15 per cent; P = 0.021) were more common with LC. Median (range) hospital stay was reduced by EC (16 (6-59) versus 18 (9-262) days; P = 0.013). Early stoma closure is feasible in selected patients, with reduced hospital stay, bowel obstruction and medical complications, but a higher wound complication rate. NCT00428636 (http://www.clinicaltrials.gov).


Relative quantification of pork and beef in meat products using global and species-specific peptide markers for the authentication of meat composition.
We used global and species-specific peptide markers for a relative quantitative determination of pork and beef in raw and processed meat products made of the two meat species. Four groups of products were prepared (i.e., minced raw meats, sausages, raw and fried burgers) in order to represent products with different extents of food processing. In each group, the products varied in the pork/beef proportions. All products were analysed by multiple reaction monitoring mass spectrometry (MRM-MS) for the presence/concentration of pork- and beef-specific peptide markers, as well as global markers - peptides widely distributed in muscle tissue. The combined MRM-MS analysis of pork-specific peptide HPGDFGADAQGAMSK, beef-specific peptide VLGFHG and global marker LFDLR offered the most reliable validation of declared pork/beef compositions across the whole range of meat products. Our work suggests that a simultaneous analysis of global and species-specific peptide markers can be used for composition authentication in commercial pork/beef products.


Robotic Curriculum Enhances Minimally Invasive General Surgery Residents' Education.
Resident education is evolving as more cases move from open to minimally invasive. Many programs struggle to incorporate minimally invasive surgery education due to increased operative time and higher cost when residents participate. The aim of this paper is to examine if the implementation of a robotics curriculum enhances minimally invasive surgical training. A retrospective review of all ventral and inguinal hernia cases performed from March 2013 to November 2017 was conducted to determine operative technique utilized (open, laparoscopic, or robotic) and resident involvement. The study cohorts surrounded the introduction of a robotic curriculum in July 2014, and the time frames examined were labeled as Before-robotic, After-robotic, and re-visited examination was done labeled Long-term. The study was performed at a large quaternary care referral center. The participants were all patients who underwent ventral and inguinal hernia repairs on the general surgery, transplant, or colorectal service. Before-robotic had 739 hernia cases performed: 642 (87%) open, 93 (13%) laparoscopic, and 4 (0.5%) robotic. After-robotic had 682 hernia cases performed: 529 (78%) open, 54 (8%) laparoscopic, and 99 (15%) robotic. Long-term had 792 hernia cases performed: 603 (76%) open, 25 (3%) laparoscopic, and 164 (21%) robotic. The general trend was towards an institutional decrease in open cases and an increase in robotic hernia cases. Resident participation in the robotics cases across all levels increased after the implementation of the robotic curriculum. Implementation of a robotic curriculum can enhance minimally invasive surgical training experience for general surgery resident education.


PTPRO suppresses lymph node metastasis of esophageal carcinoma by dephosphorylating MET.
Protein tyrosine phosphatase receptor-type O (PTPRO) is a membrane-bound tyrosine phosphatase. Notably, epigenetically silenced PTPRO due to promoter hypermethylation is frequently linked to malignancies. In this study, we used cellular and animal models, and patient samples to demonstrate that PTPRO can suppress the metastasis of esophageal squamous cell carcinoma (ESCC). Mechanistically, PTPRO can inhibit MET-mediated metastasis by dephosphorylating Y1234/1235 in the kinase activation loop of MET. Patients with PTPROlow/p-METhigh had significantly poor prognosis, suggesting that PTPROlow/p-METhigh can serve as an independent prognostic factor for patients with ESCC.


[Molecular genetic diagnosis of Stargardt disease].
To comparatively evaluate the efficacy of genetic screening in patients with Stargardt disease (SD) by using an express panel of 5 most common ABCA4 mutations and performing massive parallel sequencing of all coding regions of the ABCA4, ELOVL4, PROM1, and CNGB3 genes. MLPA analysis for 5 ABCA4 mutations, namely p.G863A, p.L541P, p.A1038V, p.G1961E, and p.P1380L, was done in 54 patients with SD. In 25 patients, massive parallel sequencing of coding regions (exons) and neighboring introns of the ABCA4, ELOVL4, PROM1, and CNGB3 genes was also performed. Gene testing for 5 ABCA4 mutations showed that 50% of patients (27 patients) harbored one mutation and 13% - two mutations. At massive parallel sequencing (25 patients), two pathogenic alleles were found in 21 patients (84%), one mutation - in 23 patients (91.7%). The majority of mutations was accounted for by the ABCA4 gene (83% of all mutation-positive patients). Sequencing of exons and neighboring introns of the ABCA4, ELOVL4, PROM1, and CNGB3 genes with the new molecular genetic diagnostic system enabled confirmation of the diagnosis of SD in 84% of patients. High prevalence of p.L541P, p.A1038V, and p.G1961E mutations of the ABCA4 gene has been established.


Effect of high dose progestin on serum lipids.
The effect of high dose medroxyprogesterone (MPA) on serum lipids was studied in 31 postmenopausal patients with endometrial cancer. After 3 months of MPA treatment, total cholesterol decreased by 18% (P less than 0.001), LDL cholesterol by 16% (P less than 0.01) and HDL cholesterol by 38% (P less than 0.001) from the respective pretreatment values; correspondingly, the ratio of HDL to total cholesterol decreased (P less than 0.001). Similar changes were found as early as 2 weeks after start of treatment. In the 15 controls receiving no progestin treatment, full dose intracavitary radiotherapy and gynecological surgery had no effect on these serum lipids.


Identification of the aged microplastics film and its sorption of antibiotics and bactericides in aqueous and soil compartments.
Here, thin-film microplastics (MPs) from black garbage bags were simulated aged by artificially ultraviolet radiation, and their sorption behavior toward antibiotics and bactericides in water and soil was explored. The chemical structure, surface functional groups, and the aged degree indicators of the identified polyethylene microplastics (PE-MPs) were studied by FT-IR spectra. The decreased crystallinity and hydrophobicity of PE-MPs-16 demonstrated by XRD and contact angle measurements and enhanced carbonyl index (0.0105) were highly related to the enhanced sorption capacities, especially for crystal violet (18.10 mg/g) in water. Moreover, PE-MPs-16 mitigated the adsorption rate and had little influence on the sorption capacity in soil. The sorption data fitted well to Henry (water) or Freundlich (soil) isotherm model, indicating the hydrophobic partition was involved in the sorption. Our research helps to clarify the interaction between MPs and organic pollutants and better understand the fate of virgin and aged PE-MPs in the varied compartments.


Vesnarinone: a new inotropic agent for treating congestive heart failure.
Vesnarinone is a new and novel inotropic drug that has unique and complex mechanisms of action. It inhibits phosphodiesterase, thereby leading to increased intracellular calcium, and also affects numerous myocardial ion channels, resulting in the prolongation of the opening time of sodium channels and the decrease in the delayed outward and inward rectifying potassium current. In vitro, it has also demonstrated significant effects on cytokine production, which may account for some of its observed clinical benefits. Hemodynamic studies in humans with congestive heart failure reveal that vesnarinone can improve ventricular function. Placebo-controlled studies in large numbers of patients with heart failure have suggested a morbidity and mortality benefit with a 60 mg daily dose. There is increased mortality with vesnarinone at the 120 mg daily dose, however, suggesting a narrow therapeutic window for the drug. Its predominant toxic side effect is a 2% incidence of reversible neutropenia.


Viability assessment of Bifidobacterium longum ATCC 15707 on non-dairy foods using quantitative fluorescence microscopy.
This study demonstrates an effective technique for separating and purifying viable bacteria from samples that interfere with viability staining. The viability of Bifidobacterium longum ATCC 15707 was assessed using Percoll Buoyant Density Gradient Centrifugation (PBDC) to separate bacteria from complex non-dairy food matrices and Quantitative Fluorescence Microscopy (QFM) to determine individual cells using LIVE/DEAD BacLight bacterial viability staining. Water agar (3%) was used to retain cells of B. longum and offered a lower fluorescence background with BacLight viability staining, compared with fixation on polycarbonate (PC) black membrane. The effect of drying temperatures and non-dairy foods on viability of B. longum was assessed. B. longum coated on oat, peanut or raisin was separated by filtration, low- and high-speed centrifugation, flotation and sedimentation buoyant density centrifugation. Purified cells were subsequently deposited on water agar for rehydration followed by LIVE/DEAD BacLight viability staining and enumeration. Conventional plate counting was also conducted to compare viability results. Finally, this method was applied to assess cell membrane damages of B. longum incorporated onto non-dairy foods during 24 h drying. Furthermore, viability assessment of B. longum coated onto oat, peanut, or raisin was much lower by plate counting compared to viability staining. Drying appeared to have a greater impact when viability was assessed by plate counting compared to viability staining. IMPORTANCE: Enumeration of viable beneficial bacteria from function foods presents a significant bottleneck for product development and quality control. Interference with microscopic and/or fluorescent techniques by ingredients, time required to incubate plated microbes, and the transient nature of the colony forming unit make rapid assessment of viable bacteria difficult. Viability assessment of Bifidobacterium longum ATCC 15707 by Percoll Buoyant Density Gradient Centrifugation with LIVE/DEAD BacLight viability staining on water agar (3%) was in agreement with serial dilution enumeration. Without the need for incubation viability assessment by staining provided a more rapid means to assess the impact of drying on the viability of B. longum coated onto oat, peanut or raisin.


A review of the genus Alulatettix Liang (Orthoptera: Tetrigoidea: Tetrigidae).
The taxonomy of the tetrigid genus Alulatettix Liang is reviewed. A new species, Alulatettix orthomarginalis n. sp. is described. The annotated list and key to all known species of Alulatettix are given.


Regional distribution of importin subtype mRNA expression in the nervous system: study of early postnatal and adult mouse.
Importin-alpha and beta1 mediate the translocation of macromolecules bearing nuclear localization signals across the nuclear pore complex. Five importin-alpha isoforms have been identified in mice and six in human. Some of these importins play an important role in neural activity such as long term potentiation, but the functional differences of each isoform in the CNS are still unclear. We performed in situ hybridization (ISH) using non-isotopic probes to clarify the expression patterns of importin-alpha subtypes (alpha5, alpha7, alpha1, alpha4, alpha3) and importin-beta1 in the mouse CNS of adult and early postnatal stages. The mRNAs of the importin-alpha subtypes and importin beta1 were expressed throughout the CNS with specific patterns; importin-alpha5, alpha7, alpha3, and beta1 showed moderate to high expression levels throughout the brain and spinal cord; importin-alpha4 showed a lack of expression in limited regions; and importin-alpha1 showed a low expression level throughout the brain and spinal cord but with a moderate expression level in the olfactory bulb and reticular system. We also demonstrated that importin-alphas and beta1 mRNAs were predominantly expressed in neurons in the adult mouse brain by using double-labeling fluorescence ISH and immunohistochemistry. Moreover, importin-alphas and beta1 mRNAs were detected throughout the CNS of postnatal mice and were highly expressed in the external granule layer of the cerebellar cortex on postnatal days 0, 4, and 10. This is the first report of importin-alphas and beta1 expression throughout the CNS of adult mice, as well as in the developing brain, including cell type specific localization.


Continuing Decline in Varicella Incidence After the 2-Dose Vaccination Recommendation-Connecticut, 2009-2014.
Background. Varicella is a highly contagious vaccine-preventable illness. In 1996, the Advisory Committee for Immunization Practices recommended 1 dose of vaccine for children, and in 2006 it recommended 2 doses; Connecticut required 1 dose for school entry in 2000 and 2 doses for school entry starting in 2011. Connecticut varicella incidence overall and among persons aged 1-14 years declined during 2005-2008. We analyzed varicella surveillance data for 2009-2014 to characterize overall and age group-specific trends in the setting of the 2-dose requirement. Methods. Passive surveillance was used to collect data and identify incidence trends and changes in proportions, and these were assessed by χ(2) tests for trend and proportion, respectively. Results. Varicella incidence decreased from 13.8 cases/100 000 persons during 2009 to 5.1 cases/100 000 persons during 2014 (P < .001); significant declines in incidence occurred among children aged 1-4, 5-9, and 10-14 years (P < .01 for each age group). Cases classified as preventable decreased from 44% during 2009 to 25% during 2014 (P < .01); significant declines in percentages of preventable cases occurred only among those aged 5-9 years (P < .05) and 10-14 (P < .01) years. Conclusions. Varicella incidence continued to decline in Connecticut in the setting of the 2-dose school-entry program. Continued surveillance is needed to assess the full influence of the 2-dose recommendation.


Structures of two O-polysaccharides of the lipopolysaccharide of Citrobacter youngae PCM 1538 (serogroup O9).
Mild acid degradation of the lipopolysaccharide of Citrobacter youngae O9, strain PCM 1538 released a homopolysaccharide of 4-acetamido-4,6-dideoxy-D-mannose (D-Rha4NAc, N-acetyl-D-perosamine). Studies by methylation analysis and (1)H and (13)C NMR spectroscopy, using two-dimensional (1)H,(1)H COSY, TOCSY, NOESY and H-detected (1)H,(13)C HSQC experiments showed the presence of two structurally different polysaccharides consisting of the following units: -->)-alpha-D-Rhap4NAc-(1 --> and --> 3)-alpha-D-Rhap4NAc-(1 --> 3)-beta-D-Rhap4NAc-(1 -->.


A Scoping Review of Ethical Considerations of Mandatory COVID-19 Vaccination of Healthcare Workers.
Duty of care is the core ethical responsibility of healthcare workers. Getting the workforce vaccinated will provide safety to the public, protect the vulnerable population and provide a safe working environment. While most agree that healthcare workers should be prioritised in the vaccination programme, mandatory vaccination remains a complicated and contentious issue with political, legal and ethical dimensions. This study aims to determine the ethical considerations associated with mandatory vaccinations among healthcare workers. A total of 152 abstracts were identified of which, 142 were excluded based on abstracts because they did not meet the inclusion criteria. The remaining ten articles were further evaluated with three articles that fit the inclusion criteria specifically discussing mandatory vaccination among healthcare workers and the ethical issues. Benefits, risks, effectiveness, equity and justice, autonomy, reciprocity and trust were used as a framework to discuss the ethical considerations which resonated both directly from the included papers, as well as more generally from the other literature associated with this search. There is limited literature on the topic of ethical considerations associated with COVID-19 mandatory vaccination of healthcare workers, as a systematic review identified only 3 papers. Benefits, risks, effectiveness, equity and justice, autonomy, reciprocity and trust were among the seven ethical considerations identified and discussed.


Phenotypic-screening generates active novel fetal globin-inducers that downregulate Bcl11a in a monkey model.
Heritable disorders associated with hemoglobin production are the most common monogenic disorders. These are mainly represented by disorders such as β-thalassemia and sickle cell disease. Induction of fetal hemoglobin (HbF) has been known to ameliorate the clinical severity of these β hemoglobinopathies. A high throughput phenotypic screening was used in this study to isolate novel compounds that may enhance the expression of γ-globin, the component of HbF, in human erythroid cell lines and primary erythroid progenitors derived from human CD34+ cells. The effect of lead compounds on epigenetic enzymes and key transcriptional factors was evaluated to identify their mode of action. One hit compound was further evaluated in vivo using monkey models. Among the ~18,000 compounds screened, 18 compounds were selected and tested to determine their ability to induce HbF in human erythroid cell lines and primary erythroid cells. One of these compounds, a 3-phenyl-isoxazole derivative, could potentially induce HbF in monkey bone marrow cells when administered orally. The compound downregulated negative transcriptional regulators of HbF, Bcl11a and LRF without inhibiting the known epigenetic enzymes. These studies demonstrated the advantages associated with phenotype-screening and identified novel fetal globin inducers that may be useful for treating hemoglobinopathies.


Application of preparative high-speed counter-current chromatography for isolation and separation of schizandrin and gomisin A from Schisandra chinensis.
Following an initial cleaning-up step on the D101 macroporous resin, a preparative high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (1:0.9:0.9:1, v/v) was used to isolate and separate schizandrin and gomisin A from Schisandra chinensis. A total of 107 mg schizandrin and 36 mg gomisin A with purities of 99.5% and 99.1% were obtained from 400 mg crude extract in one-step elution and less than 3 h, and the structure identification was performed by UV, IR, MS, 1H NMR and 13C NMR.