Five-year experience with modified Fogli (Loré's fascia fixation) platysmaplasty.
Over a 5-year period, my technique of approaching and modifying the aging neck has changed from direct suturing of the medial platysma bands and strong posterior traction of the platysma to superior elevation of the posterior platysma and strong fixation to the tympanoparotid fascia. When indicated, redundant anterior platysmal bands are resected instead of approximated. Evaluation of these anterior bands preoperatively for thickness and degree of descent allows more precise decision-making regarding the need to resect redundant and excessively thick or long anterior platysmal bands. The added advantage of the strong fixation of the platysma in a vertical fashion to Loré's fascia (the tympanoparotid fascia) leads not only to an improvement in the contour of the jawline and submental area but also to the undervalued aesthetic feature of a defined contour and visually increased length of the sternomastoid muscle.


The presence of tetracyclines and sulfonamides in swine feeds and feces: dependence on the antibiotic type and swine growth stages.
Swine farms are one of the important sources of antibiotics in the environment. In this study, 42 samples of compound feed and feces of swine collected at different growth stages from intensive farms were evaluated for the occurrence and concentrations of three tetracyclines (TCs, namely oxytetracycline, chlortetracycline, and doxycycline) and three sulfonamides (SAs, namely sulfadiazine, sulfadimidine, and sulfamethoxazole). To check for other additional sources of antibiotic administration, ratios (R) of the measured and the predicted levels of each antibiotic excreted via feces were also estimated. Our results showed that the maximum concentration of TCs was 376,210 μg kg-1 and 541,020 μg kg-1 in the feeds and feces, respectively, both for oxytetracycline. In contrast, the highest concentration of SAs were 16.98 μg kg-1 for sulfadimidine in the feeds and 14.70 μg kg-1 for sulfadiazine in the feces. The concentrations of ΣTCs (sum of the three tetracyclines) in swine feeds and feces were found to be 1-4 orders of magnitude higher than those of ΣSAs (sum of the three sulfonamides). Approximately 36% of the R values were found to be greater than one, indicating other sources of administration such as injection and/or oral administration (via drinking water) may also contribute to the presence of antibiotics in feces. Most of the higher R values were found in starter pigs, which were generally administrated with antibiotics by multiple routes to prevent disease and promote swine growth. Our study suggests that comprehensive measures may be undertaken to control antibiotic use in intensive swine farms.


Predictors of Service Utilization of Young Children and Families Enrolled in a Pediatric Primary Care Mental Health Promotion and Prevention Program.
Understanding early childhood mental health service utilization in community-based clinical settings is important. Project Linking Actions for Unmet Needs in Children's Health (Project LAUNCH) provided mental health-related services for young children and families within pediatric medical homes. Using data from the Project LAUNCH evaluation (n = 106), we implemented negative binomial regression models to determine if baseline variables were associated with service utilization, defined as the number of encounters between the family and the team. Past-year homelessness emerged as a significant predictor of service utilization. Encounters for families with children who experienced homelessness within the last 12 months occurred at a rate 34.5% lower than those who had not experienced homelessness. Results highlight the importance of addressing homelessness as a barrier to mental health service utilization for families. Screening for recent housing insecurity and developing interventions that integrate housing support services into mental health programs may inform strategies to increase attendance for families with young children.


Arsenic oxide targets stem cell marker CD133/prominin-1 in gallbladder carcinoma.
CD133+ tumor cells are responsible for the initiation, propagation and recurrence of tumors, which raises the question of how to effectively target CD133+ tumor cells. Arsenic trioxide (As2O3) has considerable efficacy in treating solid tumors with induction of apoptosis. Here, we found that purified CD133+ gallbladder carcinoma cells are highly resistant to conventional chemotherapy. However, As2O3 effectively induces CD133+ gallbladder carcinoma cells apoptosis. Treatment with As2O3 reduces CD133 expression at transcriptional levels. Furthermore, the ectopic expression of CD133 attenuated the apoptotic effect of As2O3 on cells through activation of AKT signaling pathways. Collectively, As2O3 effectively targets CD133 in gallbladder carcinoma, providing a new mechanism of As2O3-induced cell apoptosis and a better understanding of drug resistance in gallbladder carcinoma.


Identification and characterization of clinically isolated biofilm-forming gram-positive rods from teeth associated with persistent apical periodontitis.
We isolated spore-forming gram-positive aerobic rods from three patients with persistent periapical periodontitis. These cells possessed unique phenotypic characteristics by exhibiting dense meshwork-like structures on their cell surfaces that could be found in a number of biofilm-forming bacteria. We identified these strains as Bacillus subtilis by the API system and 16S ribosomal RNA gene (rRNA) sequencing. Treatment of the meshwork-like structures with protease K and staining with calcofluor for polysaccharides indicated that these structures were polysaccharides in nature and could be essential for biofilm formation by these isolates. Our findings suggest that B. subtilis could form biofilms in periapical periodontitis lesions, and this might contribute to the resistance to treatment resulting in the development of persistent periapical periodontitis observed in these patients. The particular mechanisms for B. subtilis biofilms to develop periapical periodontitis are still unknown. Further studies are needed to clarify the role of biofilms in persistent infections.


Effect of mild cognitive impairment on balance.
To investigate the effect of mild cognitive impairment (MCI) on balance. 87 subjects with subjective memory impairment were enrolled, and subdivided into two groups, MCI and non-MCI, according to diagnostic criteria of amnestic subtype of MCI according to the 1999 MCI international panel (Current Concepts in Mild Cognitive Impairment). These two groups were matched for age and gender. Posturography was used to assess balance by measuring the mediolateral and anteroposterial sway speed and distance in the standing position, with both opened and closed eyes. The mediolateral sway speed and distance were higher in the MCI group than the non-MCI group, with both opened and closed eyes (p<0.05). However, there was no significant difference between the MCI group and non-MCI in anteroposterior sway speed and distance. These results were confirmed in a multivariate model adjusting for gender, age, weight, height, foot size, and education. The mediolateral, and anteroposterior sway speed and distance values were higher on eye closing status than on eye opening status in both the MCI and control groups (p<0.00). The falling risk is assumed to be higher in MCI subjects than in non-MCI subjects, especially due to decreased mediolateral balance, as shown in our adjusted analysis. These findings underscore the importance of specific balance exercise in which mediolateral balance is measured and visual compensation training programs for MCI subjects in order to prevent fall and related fracture, as well as the importance of programs for improvement of cognitive function.


Anatomical variations of the renal artery based on the surgeon's direct observation: A French perspective.
Renal arterial vasculature presents a great anatomical variation. A good knowledge of this anatomy is essential in the field of kidney transplantation. The aim of this study is to describe the anatomical variations of the renal arterial vasculature based on the retrieved but not transplanted kidneys (RNTK) and their contralateral grafted kidneys (CGK), which anatomy is described by surgeons themselves after aortic dissection during multi-organ procurement (MOP). Using the "Crystal" database of the French "Agence de la biomédecine" (ABM), all RNTK were retrospectively selected over one year. Then, the arterial anatomy of each RNTK and their CGK was studied using the surgical and the histopathological reports. The surgical report was completed by the surgeon at the end of the MOP from deceased donors. The qualitative variables were expressed in numbers (percentage of the population) and were compared by a Chi2 test or an exact Fisher test depending on the sample size. A P-value of less than 0.05 was considered statistically significant. In total, 356 kidneys were studied (241 RNTK - 115 CGK), 69% had a single artery and 31% had multiple arteries (26% with two arteries and 5% with three or more). The incidence of multiple arteries was similar between the right and left kidneys (32% vs. 30% respectively). A modal arrangement with 1 artery on each side was present in 51% of cases. Thus, 1 in 2 donors had at least 2 arteries on one side. Multiple arteries were bilateral in 12% of cases. The RNTK group presented more kidneys with multiple arteries than the CGK group (35% vs. 22%). Our study shows a higher incidence of multiple renal arteries than the literature (31% vs. 25%). Thus, MOP can be considered as an accurate and reliable method of describing renal arterial anatomy, especially that some small arteries may be missed when using radiological or cadaveric dissection techniques.


Population pharmacokinetics of levornidazole in healthy subjects and patients, and sequential dosing regimen proposal using pharmacokinetic/pharmacodynamic analysis.
Although sequential treatment with levornidazole has been used for anaerobic infection in clinical practice, there is no evidence-based dosing regimen. This study aimed to evaluate the pharmacokinetics (PK) of levornidazole in healthy subjects and patients, and to propose an evidence-based sequential dosing regimen by pharmacokinetic/pharmacodynamic (PK/PD) analysis. A population PK model was built using the data of 116 Chinese subjects, including 88 healthy young subjects, 12 healthy elderly subjects, and 16 patients with intra-abdominal anaerobic infection. PK/PD analysis was performed combining the minimum inhibitory concentration (MIC) values of levornidazole against 375 anaerobic strains. Four sequential dosing regimens (500 mg q12h, 1000 mg loading dose followed by 500 mg q12h, 750 mg q24h, and 1000 mg q24h) were evaluated in terms of cumulative fraction of response (CFR) and probability of target attainment (PTA) by Monte Carlo simulation. The concentration data of levornidazole and its active metabolites were described adequately by two- and one-compartment models, respectively. Body weight was identified as a significant covariate of levornidazole clearance. Simulations showed that satisfactory PTA (>90%) was achieved for the four dosing regimens when MIC ≤1 mg/L. Considering the simulation results, patients' safety and compliance, levornidazole 750 mg intravenous infusion q24h for 2 days followed by 750 mg oral dose q24h for 5 days was optimal for Bacteroides spp. with an identified MIC ≤1 mg/L.


Unusual parotid tumors.
The patient presenting with a mass lesion of the parotid gland is frequently found to have a mixed tumor of salivary tissue origin. However, less common lesions occur in the anatomical region of the parotid gland. These pathological entities deserve consideration in the differential diagnosis. This report presents nine patients with unusual lesions occurring in the parotid region. These regions include cervicofacial actinomycosis, branchial cleft cyst, parapharyngeal tumors, bony lesion of the mandible, non-parotid origin malignant tumor, and metastatic malignant tumors. Each class of lesions demonstrated is also discussed.


Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial.
In the 2-year CARE-MS I and II trials, alemtuzumab 12 mg administered on 5 consecutive days at core study baseline and on 3 consecutive days 12 months later significantly improved outcomes versus subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing-remitting multiple sclerosis patients. Here, we present the final 6-year CARE-MS extension trial results (CAMMS03409), and compare outcomes over 6 years in patients randomized to both treatment groups at core study baseline. Over a 4-year extension, alemtuzumab patients (alemtuzumab-only) received as-needed additional alemtuzumab (⩾12 months apart) for disease activity after course 2. SC IFNB-1a patients who entered the extension discontinued SC IFNB-1a and received 2 alemtuzumab 12 mg courses (IFN-alemtuzumab), followed by additional, as-needed, alemtuzumab. Through year 6, 63% of CARE-MS I and 50% of CARE-MS II alemtuzumab-only patients received neither additional alemtuzumab nor other disease-modifying therapy, with lasting suppression of disease activity, improved disability, and slowing of brain volume loss (BVL). In CARE-MS I patients (treatment-naive; less disability; shorter disease duration), disease activity and BVL were significantly reduced in IFN-alemtuzumab patients, similar to alemtuzumab-only patients at year 6. Among CARE-MS II patients (inadequate response to prior treatment; more disability; longer disease duration), alemtuzumab significantly improved clinical and magnetic resonance imaging outcomes, including BVL, in IFN-alemtuzumab patients; however, disability outcomes were less favorable versus alemtuzumab-only patients. Safety profiles, including infections and autoimmunities, following alemtuzumab were similar between treatment groups. This study demonstrates the high efficacy of alemtuzumab over 6 years, with a similar safety profile between treatment groups. NCT00530348; NCT00548405; NCT00930553.


Omega-3 supplementation is neuroprotective to corneal nerves in dry eye disease: a pilot study.
To investigate whether oral, long-chain omega-3 (ω-3) essential fatty acid (EFA) supplementation, for 3 months, induces changes to the central corneal sub-basal nerve plexus in dry eye disease and whether nerve alterations correlate with clinical findings. This prospective, comparative study involved the final 12 participants enrolled in a randomised, double-masked, placebo-controlled clinical trial of 60 participants with moderate dry eye disease. Participants received either placebo (olive oil 1500 mg/day; n = 4) or ω-3 EFA supplements (~1000 mg/day eicosapentaenoic acid + ~500 mg/day docosahexaenoic acid; n = 8) for 90 days. The main outcome measure was the mean change in central corneal sub-basal plexus nerve parameters between days one and 90, quantified using in vivo confocal microscopy. Secondary outcomes included mean change in tear osmolarity, corneal dendritic cell density and basal epithelial cell density. Compared with baseline, the reduction in OSDI score and tear osmolarity at day 90 were greater in the ω-3 EFA group than the placebo group (OSDI: ω-3 EFA, mean ± SEM: -15.6 ± 2.8 vs placebo: -2.8 ± 4.1 units, t5 = 2.6, p = 0.04; tearosmolarity: ω-3 EFA: -22.63 ± 5.7 vs placebo: -8 ± 2.7 mOsmol/L, t9 = 2.3, p = 0.04). At day 90, corneal total nerve branch density (CTBD: 91.1 ± 8.6 vs 45.1 ± 13.4 branches/mm2 , F1,10 = 14, p = 0.004) and corneal nerve branch density on the main fibre (CNBD: 63.4 ± 6.5 vs 27.9 ± 11.5 branches/mm2 , F1,10 = 6, p = 0.03) were higher in the ω-3 EFA group compared with placebo. Relative to day 1, CNBD (branches/mm2 ) increased at day 90 in the ω-3 EFA group (+20.0 ± 9.2, t8 = 3.2 p = 0.01) compared with placebo (-10.8 ± 3.2). Similar changes were evident for corneal nerve fibre length (CNFL, mm/mm2 ), which increased from baseline at day 90 in the omega-3 EFA group (+2.9 ± 1.6, t8 = 3.4 p = 0.01) compared with placebo (-2.7 ± 0.5). There was a negative correlation between CTBD and tear osmolarity (r10 = -0.70, p = 0.01). No significant changes were observed for basal epithelial cell or corneal dendritic cell density. These pilot study findings suggest that ω-3 EFA supplementation imparts neuroprotective effects in the corneal sub-basal plexus that correlate with the extent of tear osmolarity normalisation.


Extramedullary versus intramedullary tibial cutting guides in megaprosthetic total knee replacement.
In a standard total knee replacement, tibial component alignment is a key factor for the long term success of the surgery. The purpose of this study is to compare the accuracy of extramedullary and intramedullary tibial cutting guides used in indigenous and imported implants respectively, in positioning of the tibial components in megaprosthetic knee replacements. A comparative study of the accuracy of extramedullary and intramedullary tibial cutting guides was carried out in 92 megaprosthetic knee replacements for distal femoral tumors. For the proximal tibia cut for tibial component placement, an extramedullary guide was used in 65 patients and an intramedullary guide was used in 27 patients. Tibial component alignment angles were measured in postoperative X-rays with the help of CAD software. There was more varus placement in coronal plane with extramedullary cutting guide (-1.18 +/- 2.4 degrees) than the intramedullary guide (-0.34 +/- 2.31 degrees) but this did not reach statistical significance. The goal of 90 +/- 2 degrees alignment of tibial component was achieved in 54% of patients in the extramedullary group versus 67% in the intramedullary group. In terms of sagittal plane alignment, extramedullary guide showed less accurate results (2.09 +/- 2.4 degrees) than intramedullary guide (0.50 +/- 3.80 degrees) for tibial component alignment, though 78% of patients were aligned within the goal of 0-5 degrees of tibial slope angle in extramedullary group versus 63% in intramedullary group. The mean error in the measurements due to rotation of the knee during taking the X-rays was less than 0.1 degrees and distribution of the X-rays with the rotation of knee was similar in both the groups. Overall, in megaprosthetic knee replacement intramedullary guides gave more accurate results in sagittal plane and exhibited similar variability as of extramedullary guides in coronal plane.


Case report: clozapine given in the context of chemotherapy for lung cancer.
Despite the frequent use of the antipsychotic medication, clozapine, in chronic treatments of psychiatric patients, there is limited clinical evidence available to guide clinicians in the problematic situation of a chemotherapy-induced blood dyscrasia. To perform a literature review and add a case report to the available clinical evidence. We gathered evidence through literature searches on Medline and with the assistance of a medical information specialist from Novartis who searched their internal database. We also report the case of a patient maintained on clozapine treatment despite full-dose chemotherapy (cisplatin and etoposide) for an extensive lung cancer. The searches returned seven clinically relevant references. These references do not establish a synergistic effect of clozapine and chemotherapy on blood counts. However, it has been shown that clozapine exposure activates common apoptotic pathways shared with anticancer drugs. Although the meagre clinical evidence precludes drawing any general conclusion as to the safety of maintaining clozapine administration during chemotherapy, it does not point to an obvious worsening of the haematological outcomes.


Association between physical activity, growth differentiation factor 15 and bodyweight in older adults: A longitudinal mediation analysis.
Late-life aging is often associated with appetite reduction and weight loss. Physical activity (PA) may prevent these processes, but the molecular mechanisms involved remain elusive. The present study investigated the putative mediating aspect of growth differentiation factor 15 (GDF-15), a stress signalling protein involved in aging, exercise and appetite control, on the association between PA and late-life-associated weight loss. One thousand eighty-three healthy adults (63.8% women) aged 70 years and over who participated in the Multidomain Alzheimer Preventive Trial were included. Bodyweight (kg) and PA levels (square root of metabolic equivalent of task-min/week) were assessed repeatedly from baseline to the 3-year visit, whereas plasma GDF-15 (pg/mL) was measured at the 1-year visit. Multiple linear regressions were performed to test the association between first-year mean PA level, 1-year visit GDF-15 concentration and subsequent bodyweight changes. Mediation analyses were used to investigate whether GDF-15 mediated the association between first-year mean PA levels and consecutive bodyweight changes. Multiple regression analyses demonstrated that higher first-year mean PA levels significantly predicted lower GDF-15 and bodyweight at 1 year (B = -2.22; SE = 0.79; P = 0.005). In addition, higher 1-year visit GDF-15 levels were associated with faster subsequent bodyweight loss (Time × GDF-15 interaction B = -0.0004; SE = 0.0001; P = 0.003). Mediation analyses confirmed that GDF-15 mediated the association between first-year mean PA levels and subsequent bodyweight changes (mediated effect ab = 0.0018; bootstrap SE = 0.001; P < 0.05) and revealed that mean PA had no direct effect on subsequent bodyweight changes (c' = 0.006; SE = 0.008; P > 0.05). This study suggests that GDF-15 may be one of the molecules mediating the link between PA and late-life weight loss, but mechanistic studies are necessary to further support the present findings.


Alcohol-preferring P rats exhibit aversion-resistant drinking of alcohol adulterated with quinine.
Understanding why some people continue to drink alcohol despite negative consequences and others do not is a central problem in the study of alcohol use disorder (AUD). In this study, we used alcohol-preferring P rats (a strain bred to prefer to drink alcohol, a model for genetic risk for AUD) and Wistar rats (control) to examine drinking despite negative consequences in the form of an aversive bitter taste stimulus produced by quinine. Animals were trained to consume 10% ethanol in a simple Pavlovian conditioning task that paired alcohol access with an auditory stimulus. When the alcohol was adulterated with quinine (0.1 g/L), P rats continued to consume alcohol + quinine at the same rate as unadulterated alcohol, despite a demonstrated aversion to quinine-adulterated alcohol when given a choice between adulterated and unadulterated alcohol in the home cage. Conversely, Wistar rats decreased consumption of quinine-adulterated alcohol in the task, but continued to try the alcohol + quinine solution at similar rates to unadulterated alcohol. These results indicate that following about 8 weeks of alcohol consumption, P rats exhibit aversion-resistant drinking. This model could be used in future work to explore how the biological basis of alcohol consumption and genetic risk for excessive drinking lead to drinking that is resistant to devaluation.


An inverse correlation between loop length and stability in a four-helix-bundle protein.
The loops in proteins are less well characterized than the secondary structural elements that they connect. We have used the four-helix-bundle protein Rop as a model system in which to explore the role of loop length in protein folding and stability. A natural two-residue loop was replaced with a series of glycine linkers up to 10 residues in length. All 10 mutants are highly helical dimers that retain wild-type RNA-binding activity. As loop length is increased, the stability of Rop toward thermal and chemical denaturation is progressively decreased. All the mutants assume a wild-type-like structure, which suggests that the natural loop does not actively dictate the final protein fold. The strong inverse correlation observed between loop length and stability is well described by a simple polymer model in which the entropy of loop closure is the dominant energetic term. Our results emphasize the importance of optimization of loop length to successful protein design.


A meta-analysis of parent training: moderators and follow-up effects.
A meta-analysis of 63 peer-reviewed studies evaluated the ability of parent training programs to modify disruptive child behaviors and parental behavior and perceptions. This analysis extends previous work by directly comparing behavioral and nonbehavioral programs, evaluating follow-up effects, isolating dependent variables expressly targeted by parent training, and examining moderators. Effects immediately following treatment for behavioral and nonbehavioral programs were small to moderate. For nonbehavioral programs, insufficient studies precluded examining follow-up effects. For behavioral programs, follow-up effects were small in magnitude. Parent training was least effective for economically disadvantaged families; importantly, such families benefited significantly more from individually delivered parent training compared to group delivery. Including children in their own therapy, separate from parent training, did not enhance outcomes.


Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family.
To characterize the biological activity of tocilizumab, a humanized anti-human interleukin-6 receptor (IL-6R) monoclonal antibody, we examined its binding activity to both soluble IL-6R (sIL-6R) and membrane bound IL-6R (mIL-6R) and its neutralizing activity to other IL-6 family cytokines. ELISA assay demonstrated that tocilizumab bound to sIL-6R and inhibited IL-6 binding to sIL-6R in a dose-dependent manner. The dissociation constant (Kd value) for IL-6R was determined to be 2.54+/-0.12 nmol/L by Scatchard analysis. In addition, tocilizumab had the ability to dissociate IL-6 and sIL-6R from their preformed complex. The immune complex of tocilizumab and sIL-6R did not transmit signaling. Moreover, tocilizumab suppressed the IL-6/sIL-6R complex-induced proliferation of human gp130-transfected cell, BAF-h130. In addition, tocilizumab had the ability to bind to human IL-6R expressing COS-7 cells and to suppress the growth of the IL-6-dependent myeloma cell line, KPMM2. Finally, to analyze the specificity of this antibody, the effects on signal transduction of IL-6 family cytokines such as interleukin-11 (IL-11), oncostatin M (OSM), leukemia inhibitory factor (LIF), and ciliary neurotrophic factor (CNTF) were examined using murine transfectant cell lines (BaF/IL-6R, BaF/IL-11R, BaF/OSMR, BaF/LIFR and BaF/CNTFR) that proliferate depending on IL-6, IL-11, OSM, LIF and human CNTF, respectively. Tocilizumab inhibited the proliferation of BaF/IL-6R induced by IL-6, but did not inhibit the proliferation of BaF/IL-11R, BaF/OSMR, BaF/LIFR and BaF/CNTFR cells induced by their corresponding cytokines. These lines of evidence indicate that tocilizumab is able to bind to both sIL-6R and mIL-6R and to inhibit IL-6 binding to its receptors, leading to the blockade of the IL-6 signaling through both sIL-6R and mIL-6R, but not block the signaling of other IL-6 family cytokines.


Modelling the association between COVID-19 transmissibility and D614G substitution in SARS-CoV-2 spike protein: using the surveillance data in California as an example.
The COVID-19 pandemic poses a serious threat to global health, and pathogenic mutations are a major challenge to disease control. We developed a statistical framework to explore the association between molecular-level mutation activity of SARS-CoV-2 and population-level disease transmissibility of COVID-19. We estimated the instantaneous transmissibility of COVID-19 by using the time-varying reproduction number (Rt). The mutation activity in SARS-CoV-2 is quantified empirically depending on (i) the prevalence of emerged amino acid substitutions and (ii) the frequency of these substitutions in the whole sequence. Using the likelihood-based approach, a statistical framework is developed to examine the association between mutation activity and Rt. We adopted the COVID-19 surveillance data in California as an example for demonstration. We found a significant positive association between population-level COVID-19 transmissibility and the D614G substitution on the SARS-CoV-2 spike protein. We estimate that a per 0.01 increase in the prevalence of glycine (G) on codon 614 is positively associated with a 0.49% (95% CI: 0.39 to 0.59) increase in Rt, which explains 61% of the Rt variation after accounting for the control measures. We remark that the modeling framework can be extended to study other infectious pathogens. Our findings show a link between the molecular-level mutation activity of SARS-CoV-2 and population-level transmission of COVID-19 to provide further evidence for a positive association between the D614G substitution and Rt. Future studies exploring the mechanism between SARS-CoV-2 mutations and COVID-19 infectivity are warranted.


Unintentional Injuries and Sociodemographic Factors among Households in Ethiopia.
Unintentional injuries are a public health problem throughout the world including Africa. Most of the injury studies in Ethiopia are from the healthcare facility or workplace that does not reflect the problem at the community level. Therefore, this study aimed to assess the unintentional injuries and sociodemographic factors among households in Ethiopia. This study was done from the Ethiopian Demographic and Health Survey conducted in 2016. The survey collected information about unintentional injuries and injury mechanisms in the past 12 months among 16,650 households. The selection of households was from nine regions and two city administrations of Ethiopia using a stratified cluster sampling procedure. Descriptive statistics were used to characterize the data and the chi-square test was applied as a test of significance and a p value of <0.05 was considered statistically significant. Of the 16,650 households that participated in the study, 394 (2.4%) reported that at least one household member suffered from an unintentional injury in the past 12 months. The leading mechanisms of injury were unintentional falls (152 falls, 33.2%) and road traffic incidents (96 incidents, 21.0%). Among household members who were injured, 84.3% survived and 15.7% died because of the injury. Divorce marital status of the household head [AOR: 2.12, 95% CI (1.12-4.41)] and family size of the household ≥ 6 [AOR:1.65, 95% CI (1.21-2.26)] were associated with high likelihood of occurrence of an injury, while lowest household wealth index [AOR: 0.69, 95% CI (0.50-0.95)] was protective against injuries. A low prevalence of unintentional injury was found from the community in this survey, which might be due to the tendency of the community to report severe injuries. Fall and road traffic accidents were the leading mechanisms of selected sociodemographic factors of the households that were associated with unintentional injuries. Injury prevention efforts should focus on falls and transportation injuries with special attention to the sociodemographic context of the communities.


A simplified method for hatching and isolating Toxocara canis larvae to facilitate excretory-secretory antigen collection in vitro.
Human toxocariasis causes several dangerous syndromes that can involve the viscera, vision and central nervous system. Diagnosing toxocariasis requires the identification of antibodies against Toxocara canis or Toxocara cati excretions and secretions (ES). To obtain ES it is necessary to collect a large number of larvae. However, since the earliest work describing the culture of Toxocara larvae, few advances in the method have been made. It has been suggested that carbon dioxide triggers molecular mechanisms that enable nematode hatching. A similar hypothesis has been made regarding Giardia excystation. To test the hypothesis we used the Giardia excystation HBSS method to hatch embryonated T. canis eggs. We found that the HBSS method was more effective than the original De Savigny method. Our results suggest that both parasites require stimulation in an acidic environment, and the abrupt change to a basic milieu in duodenum. This physiological adaptation is successful to exploit the intestinal habitat.


6-Gingerol protects cardiomyocytes against hypoxia-induced injury by regulating the KCNQ1OT1/miR-340-5p/PI3K/AKT pathway.
Hypoxia could induce cardiomyocytes injury and lead to heart disease. Studies have shown that 6-Gingerol has a protective effect on cardiomyocytes injury, but its molecular mechanism is still unclear. Cell counting kit 8 (CCK8) and flow cytometry assays were used to measure the viability and apoptosis of cardiomyocytes. Western blot (WB) analysis was performed to assess the levels of proliferation, apoptosis, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway-related proteins. The reactive oxygen species (ROS) level, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were detected by their corresponding Assay Kits. Besides, the expression levels of potassium voltage-gated channel subfamily Q member 1 opposite strand 1 (KCNQ1OT1) and microRNA-340-5p (miR-340-5p) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to verify the interaction between KCNQ1OT1 and miR-340-5p. Hypoxia could inhibit the viability and enhance the apoptosis and oxidative stress of cardiomyocytes to induce cardiomyocytes injury, while 6-Gingerol could alleviate this effect. Overexpression of KCNQ1OT1 aggravated hypoxia-induced cardiomyocytes injury and reversed the protective effect of 6-Gingerol on cardiomyocytes injury. Besides, miR-340-5p could be sponged by KCNQ1OT1, and its overexpression could invert the promotion effect of KCNQ1OT1 overexpression on hypoxia-induced cardiomyocytes injury. Moreover, miR-340-5p expression was regulated by 6-Gingerol and KCNQ1OT1. In addition, hypoxia inactivated the PI3K/AKT signaling pathway, whereas 6-Gingerol and miR-340-5p could reverse this effect. 6-Gingerol could hinder the expression of KCNQ1OT1 to protect cardiomyocytes from hypoxia-induced injury through regulation of the miR-340-5p/ PI3K/AKT pathway, providing a new mechanism of 6-Gingerol protecting cardiomyocytes from injury.


Effects of Three Interventions Combining Impact or Walking at Intense Pace Training, with or without Calcium and Vitamin Supplements, to Manage Postmenopausal Women with Osteopenia and Osteoporosis.
The purpose was to assess the effects of three interventions on bone mineral density (BMD) to prevent the onset or progression of osteoporosis in postmenopausal women. Specifically, thirty-nine postmenopausal women, diagnosed with osteopenia or osteoporosis, implemented either high-impact training (G1), the same training + calcium and vitamin D intake (G2), or walked at an intense pace + calcium and vitamin D (G3). Baseline change (BC) in BMD was estimated using the femoral neck and lumbar spine T-scores. Participants were classified as having suffered fractures and/or falls before (24-month) and during the 2-year intervention. The participants-aged 61.8 years-were allocated into G1 (n = 9), G2 (n = 16), and G3 (n = 14). The groups evolved similarly over time; however, participants in G2 exhibited the largest T-score improvements with BC over 20%. G1 and G3 maintained BMD levels (BC = -7 to 13.3%; p > 0.05). Falls occurred similarly across the interventions, while the participants in G2 had the lowest percentage of fracture events (p = 0.037). Overall, the findings suggest that regular physical exercise may be effective in maintaining or improving BMD in postmenopausal women presenting with osteopenia or osteoporosis. Due to the limited sample size, the results are preliminary and warrant future randomized trials to validate the findings.


Anterior tibial compartment syndrome following use of MAST suit.
A case of anterior tibial compartment syndrome following the use of the military antishock trousers (MAST) suit is reported. Early recognition of this complication is necessary to ensure a good outcome. Monitoring of the MAST pressure and use of the lowest pressure that is effective may decrease the likelihood of this complication.


Prevalence of Cardiac Arrhythmias and Distal Conduction Disorders in Patients With Chronic Chagas' Disease and Elevated Autoantibodies Against M2 Muscarinic Acetylcholine Receptors.
Chagas' disease (ChD) is a parasitic disease endemic to regions of Latin America and with an increasingly global reach. Up to 30% of patients with ChD develop severe dilated cardiomyopathy, ventricular arrhythmias, conduction disorders and/or sudden cardiac death. Autoantibodies against M2 muscarinic acetylcholine receptors (M2 mAChR) have been implicated in the pathogenesis of ChD. We sought to understand whether there was an association between anti-M2 mAChR autoantibody titers in patients with chronic ChD and the presence of distal cardiac conduction disorders or cardiac arrhythmias. We conducted a cross-sectional study in 79 patients from Argentina and Bolivia with chronic ChD without evident structural heart disease. Autoantibody titers were measured using indirect enzyme-linked immunosorbent assay. Elevated anti-M2 mAChR autoantibody titers were associated with the presence of distal conduction disease but not with cardiac arrhythmias. High anti-M2 mAChR autoantibody levels could assist with identifying early structural heart disease in patients with chronic ChD.


Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor.
The α7 nicotinic acetylcholine receptor is involved in neurological, neurodegenerative, and inflammatory disorders. It operates both as a ligand-gated cationic channel and as a metabotropic receptor in neuronal and non-neuronal cells. As protein phosphorylation is an important cell function regulatory mechanism, deciphering how tyrosine phosphorylation modulates α7 dual ionotropic/metabotropic molecular function is required for understanding its integral role in physiological and pathological processes. α7 single-channel activity elicited by ACh appears as brief isolated openings and less often as episodes of few openings in quick succession. The reduction of phosphorylation by tyrosine kinase inhibition increases the duration and frequency of activation episodes, whereas the inhibition of phosphatases has the opposite effect. Removal of two tyrosine residues at the α7 intracellular domain recapitulates the effects mediated by tyrosine kinase inhibition. The tyrosine-free mutant receptor shows longer duration-activation episodes, reduced desensitization rate and significantly faster recovery from desensitization, indicating that phosphorylation decreases α7 channel activity by favoring the desensitized state. However, the mutant receptor is incapable of triggering ERK1/2 phosphorylation in response to the α7-agonist. Thus, while tyrosine phosphorylation is absolutely required for α7-triggered ERK pathway, it negatively modulates α7 ionotropic activity. Overall, phosphorylation/dephosphorylation events fine-tune the integrated cell response mediated by α7 activation, thus having a broad impact on α7 cholinergic signaling.


Post-error Slowing During Instrumental Learning is Shaped by Working Memory-based Choice Strategies.
Post-error slowing (PES) - a relative increase in response time for a decision on trialtgiven an error on trialt - 1 - is a well-known effect in studies of human decision-making. Post-error processing is reflected in neural signatures such as reduced activity in sensorimotor regions and increased activity in medial prefrontal cortex. PES is thought to reflect the deployment of executive resources to get task performance back on track. This provides a general account of PES that cuts across perceptual decision-making, memory, and learning tasks. With respect to PES and learning, things are complicated by the fact that learning often reflectsmultiple qualitatively different processes with distinct neural correlates. It is unclear if multiple processes shape PES during learning, or if PES reflects a policy for reacting to errors generated by one particular process (e.g., cortico-striatal reinforcement learning). Here we provide behavioral and computational evidence that PES is influenced by the operation of multiple distinct processes. Human subjects learned a simple visuomotor skill (arbitrary visuomotor association learning) under low load conditionsmore amenable to simple working memory-based strategies, and high load conditions that were putatively more reliant on trial-by-trial reinforcement learning. PES decreased withload, even when the progress of learning (i.e., reinforcement history) was accounted for. This result suggested that PES during learning is influenced by the recruitment of working memory. Indeed, observed PES effects were approximated by a computational model with parallel working memory and reinforcement learning systems that are differentially recruited according to cognitive load.


Physical capacity increase in patients with heart failure is associated with improvement in muscle sympathetic nerve activity.
Exercise training improves physical capacity in patients with heart failure with reduced ejection fraction (HFrEF), but the mechanisms involved in this response is not fully understood. The aim of this study was to determine if physical capacity increase in patients HFrEF is associated with muscle sympathetic nerve activity (MSNA) reduction and muscle blood flow (MBF) increase. The study included 124 patients from a 17-year database, divided according to exercise training status: 1) exercise-trained (ET, n = 83) and 2) untrained (UNT, n = 41). MSNA and MBF were obtained using microneurography and venous occlusion plethysmography, respectively. Physical capacity was evaluated by cardiopulmonary exercise test. Moderate aerobic exercise was performed 3 times/wk. for 4 months. Exercise training increased peak oxygen consumption (V̇O2, 16.1 ± 0.4 vs 18.9 ± 0.5 mL·kg-1·min-1, P < 0.001), LVEF (28 ± 1 vs 30 ± 1%, P = 0.027), MBF (1.57 ± 0.06 vs 2.05 ± 0.09 mL.min-1.100 ml-1, P < 0.001) and muscle vascular conductance (MVC, 1.82 ± 0.07 vs 2.45 ± 0.11 units, P < 0.001). Exercise training significantly decreased MSNA (45 ± 1 vs 32 ± 1 bursts/min, P < 0.001). The logistic regression analyses showed that MSNA [(OR) 0.921, 95% CI 0.883-0.962, P < 0.001] was independently associated with peak V̇O2. The increase in physical capacity provoked by aerobic exercise in patients with HFrEF is associated with the improvement in MSNA.


B cell activation by the nontransforming P3HR-1 substrain of the Epstein-Barr virus (EBV).
The P3HR-1 substrain of Epstein-Barr virus does not transform B cells. This defect is known to be determined by the loss of the coding sequence for the nuclear antigen EBNA-2. The virus can attach to and enter resting B cells. The initial events after EBV infection are reminiscent of those induced by polyclonal B cell activators. Similar to the effect of these, P3HR-1 virus lowers membrane IgD expression on B cells and abrogates the transient elevation of activation markers BB-1 and LB-1 induced by the culture conditions. An important event of B cell activation is the acquisition of competence to respond to specific growth factors produced by T cells. This was induced by the P3HR-1 virus. The infected B cells had elevated [3H]thymidine incorporation when exposed to the supernatant of PHA-treated T cells. The EBV receptor is identical with the complement receptor CR2. Ligand binding to CR2 has been shown both with mouse and human B cells to deliver certain activation signals. Therefore, it is possible that the early step of activation by EBV is initiated through the binding to the receptor and is thus a cell surface event.


Resilience, stress, and psychological well-being in nursing students: A systematic review.
Synthesize the evidence relating to the interaction of resilience, stress, and well-being in undergraduate nursing students across countries. Systematic review DATA SOURCES: Peer reviewed studies published from 2008 to December 2018 were searched in CINAHL, Web of Science, Medline (OVID), PsycINFo and four biomedical databases originating from China (China National Knowledge Infrastructure, WanFang Data, VIP and CMB). Adhering to the preferred reporting items for Systematic Reviews and Meta-analyses guidelines, eight databases were searched. Twelve studies, which met the inclusion criteria, were extracted, and subject to quality appraisal by two researchers. In total, 12 papers were included. Outcome analysis revealed the level of resilience as moderate; stress levels were high and the incidence of negative psychological health accounts for a proportion of nursing students. The interaction between resilience and stress and well-being was high. Resilience and low stress were found to better predict well-being. All the studies cited recommendations to inform educational policy and practice in relation to resilience, well-being, and stress among undergraduate nursing students. This was the first systematic review to synthesize the evidence relating to the interaction of resilience, stress, and well-being in undergraduate nursing students across cultural settings. Evidence confirms the importance of resilience in nursing students influencing stress and psychosocial morbidity. Nursing educational strategies that foster and enhance resilience is recommended.


Employing salt-tolerant bacteria Serratia marcescens subsp. SLS for biodegradation of oily kitchen waste.
The high oil and salt content of kitchen waste (KW) inhibit bioconversion and humus production. To efficiently degrade oily kitchen waste (OKW), a halotolerant bacterial strain, Serratia marcescens subsp. SLS which could transform various animal fats and vegetable oils, was isolated from KW compost. Its identification, phylogenetic analysis, lipase activity assays, and oil degradation in liquid medium were assessed, and then it was employed to carry out a simulated OKW composting experiment. In liquid medium, the 24 h degradation rate of mixed oils (soybean oil: peanut oil: olive oil: lard = 1:1:1:1, v/v/v/v) was up to 87.37% at 30 °C, pH 7.0, 280 rpm, 2% oil concentration and 3% NaCl concentration. The ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS) method demonstrated that the mechanism of SLS strain metabolizing long-chain triglycerides (TAGs) (C53-C60), especially the biodegradation of TAG (C18:3/C18:3/C18:3) by the strain can reach more than 90%. Degradation of 5, 10, 15% concentrations of total mixed oil were also calculated to be 64.57, 71.25, 67.99% respectively after a simulated composting duration of 15 days. The results suggest that the isolated strain of S. marcescens subsp. SLS is suitable for OKW bioremediation in high NaCl concentration within a reasonably short period of time. The findings introduced a salt-tolerant and oil-degrading bacteria, providing insights into the mechanism of oil biodegradation and offering new avenues of study for OKW compost and oily wastewater treatment.


A holder for Ralph knives for cutting sections for high performance optical microscopy with a Minot type microtome.
We present plans for an original holder for long-edged glass knives (Ralph knives). Knives are prepared by hand-breaking of commercial window glass (3 mm thick), for cutting large blocks of tissue embedded in a water-miscible plastic resin, glycol methacrylate.


Characterization of a compressively sampled photonic link.
The emerging field of compressive sampling has potentially powerful implications for the design of analog-to-digital sampling systems. In particular, the mathematics of compressive sampling suggests that one can recover a signal at a smaller sampling interval than is dictated by the rate at which the samples are digitized. In a recent work the authors presented an all-photonic implementation of such a system and experimentally demonstrated the basic operating principles. This paper offers a more in-depth study of the system, including a more detailed description of the hardware, issues involved in real-time implementation, and how choice of signal model and model fidelity can influence the reconstruction.


Systemic upregulation of neutrophil α-defensins and serine proteases in neutrophilic asthma.
The well-characterised airway inflammatory phenotypes of asthma include eosinophilic, neutrophilic, mixed eosinophilic/neutrophilic and paucigranulocytic asthma, identified based on the proportion of sputum granulocytes. Systemic inflammation is now recognised as an important part of some airway diseases, but the involvement of systemic inflammation in the pathogenesis of airway inflammatory phenotypes of asthma remains unknown. Induced sputum samples and peripheral blood were collected from participants with asthma (n=36). Airway inflammatory cell counts were performed from induced sputum and inflammatory phenotype assigned based on the airway eosinophil and neutrophil cut-offs of 3% and 61%, respectively. RNA was extracted from whole blood and gene expression profiles were generated (Illumina Humanref-8 V3) and analysed using GeneSpring GX11. There were six genes classified as differentially expressed between the four asthma phenotypes, including the α-defensins (DEFA) 1, 1B, 3 and 4 and neutrophil proteases cathepsin G (CTSG) and elastase (ELA2). Systemic expression of DEFA1,1B,3,4,CTSG and ELA2 was significantly higher in the neutrophilic asthma (NA) phenotype. Microarray results of the α-defensins and neutrophil proteases were successfully validated using real-time PCR. Plasma elastase was significantly increased in people with neutrophilic airway inflammation. There is systemic upregulation of α-defensin and neutrophil protease expression in NA, which may represent proinflammatory effects on the bone marrow and the release of immature neutrophils into the circulation. This demonstrates a systemic inflammatory component in NA that further differentiates this from other asthma phenotypes and indicates different mechanisms in NA.


Modeling integrated stress, sleep, fear and neuroimmune responses: Relevance for understanding trauma and stress-related disorders.
Sleep and stress have complex interactions that are implicated in both physical diseases and psychiatric disorders. These interactions can be modulated by learning and memory, and involve additional interactions with the neuroimmune system. In this paper, we propose that stressful challenges induce integrated responses across multiple systems that can vary depending on situational variables in which the initial stress was experienced, and with the ability of the individual to cope with stress- and fear-inducing challenges. Differences in coping may involve differences in resilience and vulnerability and/or whether the stressful context allows adaptive learning and responses. We provide data demonstrating both common (corticosterone, SIH and fear behaviors) and distinguishing (sleep and neuroimmune) responses that are associated with an individual's ability to respond and relative resilience and vulnerability. We discuss neurocircuitry regulating integrated stress, sleep, neuroimmune and fear responses, and show that responses can be modulated at the neural level. Finally, we discuss factors that need to be considered in models of integrated stress responses and their relevance for understanding stress-related disorders in humans.


Interlaminar Shear Characteristics of Typical Polyurethane Mixture Pavement.
Polyurethane (PU) can be used as a road material binder, and its mechanical properties, durability, temperature stability, and other road performance metrics are good. However, the interlayer bonding between PU mixtures and asphalt mixtures is poor. The influence of the pavement structure, interlayer treatment scheme, load, and environmental factors on the interlayer shear characteristics of PU mixture composite pavement is analysed. Further, dynamic modulus, Hamburg rutting, accelerated loading, and inclined shear tests were conducted, and the typical PU mixture pavement shear stress was calculated. The interlaminar shear stress of double layer PU mixture pavement, polyurethane-asphalt composite pavement, and typical asphalt pavement were calculated. The results showed that the PU mixture has a low rutting deformation rate, stable mechanical properties, and strong resistance to the coupled action of temperature, water, and loading. The double-layer PU mixture structure has good water-temperature stability and fatigue resistance; however, freeze-thaw and accelerated loading cause great damage to the double-layer PU mixture structure. The residual shear strength ratio after freeze-thaw cycles and accelerated loading is only 50.3% and 35.6%, respectively, while the influence on the double-layer asphalt mixture structure is less. The theoretical calculation results of different pavement structures show that when the temperature increases from 10 °C to 50 °C, the interlaminar shear stress of polyurethane-asphalt composite pavement increases by about 20%. Additionally, the shear stress of pavement PU mixture pavement and typical asphalt pavement is mainly affected by load, and the temperature changes have an obvious effect on the interlayer shear stress of polyurethane-asphalt composite pavement. The calculated maximum shear stress of the three pavement structures with different working conditions is less than the interlaminar shear strength measured by the inclined shear test, indicating that the interlaminar treatment scheme of composite specimens can meet the shear resistance requirements of the three typical pavement structure types.


Work conflict: Another trigger to smartphone addiction of individuals with high rumination?
With the widespread use of smartphones, many people spend much time on smartphones for shopping, learning, socializing, and so on, which can affect an individual's mental health and work performance. Especially, individual perceived conflict at work may increase their social anxiety and thus raise the risk of their smartphone addiction. This study collected data from 577 corporate employees in China through convenience sampling to explain the influence mechanism of work conflict on smartphone addiction and to verify the moderating role of rumination. Statistical results show that relationship conflicts, task conflicts, and process conflicts positively affect smartphone addiction by enhancing social anxiety. Moreover, rumination positively moderates the relationship between work conflict and smartphone addiction. People with high rumination are more likely to escape reality due to conflict at work, which further enhances their smartphone addiction behaviors. Our study suggests that a relatively harmonious working atmosphere should be established within organizations, especially for employees with rumination. Work conflict is a predisposing factor for social anxiety and smartphone addiction in individuals with high rumination.


In silico prediction of drug-induced ototoxicity using machine learning and deep learning methods.
Drug-induced ototoxicity has become a serious global problem, because of leading to deafness in hundreds of thousands of people every year. It always results from exposure to drugs or environmental chemicals that cause the impairment and degeneration of the inner ear. Herein, we focused on the in silico modeling of drug-induced ototoxicity of chemicals. We collected 1,102 ototoxic medications and 1,705 non-ototoxic drugs. Based on the data set, a series of computational models were developed with different traditional machine learning and deep learning algorithms implemented on an online chemical database and modeling environment. Six ML models performed best on 5-fold cross-validation and test set. A consensus model was developed with the best individual models. These models were further validated with an external validation. The consensus model showed best predictive ability, with high accuracy of 0.95 on test set and 0.90 on validation set. The consensus model and the data sets used for model development are available at https://ochem.eu/model/46566321. Besides, 16 structural alerts responsible for drug-induced ototoxicity were identified. We hope the results could provide meaningful knowledge and useful tools for ototoxicity evaluation in drug discovery and environmental risk assessment.


Tako tsubo cardiomyopathy (transient left ventricular apical ballooning): case report of a myocardial perfusion echocardiogram study.
We are reporting a case of Tako tsubo cardiomyopathy (transient left ventricular apical ballooning) in the Western population identified by a perfusion echocardiogram that demonstrated perfusion defect at baseline in the apical and adjacent walls that was incongruous to the wall-motion abnormality. The perfusion defect improved within 72 hours on a repeated study indicating that microvasculature disruption is a key feature of this enigmatic cardiomyopathy.


Generation of hydroxyl radicals by metal-free bifunctional electrocatalysts for enhanced organics removal.
Low yields of H2O2 and a narrow range of appropriate pH values have been two major drawbacks for electro-Fenton (EF) process. Herein, metal-free electrochemical advanced oxidation processes (EAOPs) were developed with nitrogen and sulfur co-doped electrochemically exfoliated graphene (N, S-EEGr) electrocatalysts, which was confirmed as an outstanding bifunctional catalyst for synchronous generation and activation of H2O2 via (2 + 1) e- consecutive reduction reactions. Specifically, two elements (N, S) in metal-free N, S-EEGr-CF cathode synergize to promote the formation of H2O2 followed by its activation. With N, S-EEGr-CF cathode, phenol of initial 50 mg L-1 could be effectively removed within pH 3-11 and 6.25 mA cm-2, and 100% removal efficiency could be achieved within 15-min even at neutral pH. The pseudo-first-order rate constant for phenol removal in metal-free EAOPs with N,S-EEGr-CF at neutral pH was 10 times higher than that with EF process. Detection of active species, coupled with decay kinetics with specific trapping agents, confirmed that OH was the dominant oxidizing species promoting removal efficiencies of organics (phenol, antibiotics and dyes) at pH 3 and pH 7. In the actual wastewater treatment, the synergistic effect of bifunctional catalyst would also be used for improving the degradation efficiency of organics. Thus, the metal-free EAOPs with N,S-EEGr-CF cathode may serve as an alternative in wastewater treatment with a broadened range of solution pH values and avoiding Fe2+ (catalyst) addition.


Sex-related differences in the effects of aspirin on the interaction of platelets with subendothelium.
Using the Baumgartner perfusion technique, marked sex-related differences in the extent of platelet-subendothelium interaction and in the effect of aspirin (ASA) have been observed. The administration of ASA (150 mg daily for 15 days) to two groups of healthy volunteers, one composed of males and the other of females, proved to block the generation of TXB2 in both cases. The basic pattern of platelet subendothelium interaction, however, was found to be markedly different in both groups studied. In men, aspirin treatment induced a significant reduction in the percentage of platelet thrombi, whereas in women, post ASA values remained at the same level as in control experiments. These results show that in the Baumgartner perfusion system women display a less thrombogenic tendency than men and that 150 mg of ASA administered daily are effective in reducing the extent of platelet-subendothelium interaction in the male group but not in the female group. These findings could explain the absence of benefit observed for women in clinical trials with aspirin.


[Periorbital necrotizing fasciitis: a complication of a dacryocystorhinostomy].
We report a rare case of periorbital necrotizing fasciitis following a dacryocystorhinostomy procedure. We describe the common features of this rare infection of the skin and subcutaneous tissues and discuss the different management strategies as well as the controversial role of anti-inflammatory medication in treating this condition.


Polypseudorotaxane and polydopamine linkage-based hyaluronic acid hydrogel network with a single syringe injection for sustained drug delivery.
Polypseudorotaxane structure and polydopamine bond-based crosslinked hyaluronic acid (HA) hydrogels including donepezil-loaded microspheres were developed for subcutaneous injection. Both dopamine and polyethylene glycol (PEG) were covalently bonded to the HA polymer for catechol polymerization and inclusion complexation with alpha-cyclodextrin (α-CD), respectively. A PEG chain of HA-dopamine-PEG (HD-PEG) conjugate was threaded with α-CD to make a polypseudorotaxane structure and its pH was adjusted to 8.5 for dopamine polymerization. Poly(lactic-co-glycolic acid) (PLGA)/donepezil microsphere (PDM) was embedded into the HD-PEG network for its sustained release. The HD-PEG/α-CD/PDM 8.5 hydrogel system exhibited an immediate gelation pattern, injectability through single syringe, self-healing ability, and shear-thinning behavior. Donepezil was released from the HD-PEG/α-CD/PDM 8.5 hydrogel in a sustained pattern. Following subcutaneous injection, the weight of excised HD-PEG/α-CD/PDM 8.5 hydrogel was higher than the other groups on day 14. These findings support the clinical feasibility of the HD-PEG/α-CD/PDM 8.5 hydrogel for subcutaneous injection.


Identifying facilitators and barriers for adolescents participating in a school-based HIIT intervention: the eXercise for asthma with commando Joe's® (X4ACJ) programme.
High-intensity interval training (HIIT) elicits numerous health benefits, but little evidence is available regarding the feasibility of delivering school-based HIIT interventions. The aim of this study was to explore adolescents' perceptions of a 6-month, 3 × 30-min sessions per week, HIIT intervention delivered either before or after school. Eighty adolescents allocated to the intervention group (13.3 ± 1.0 years; 45 boys) were invited to take part in semi-structured focus groups post-intervention. Participants were categorised as attendees (≥40% attendance) or non-attendees (< 5% attendance). Data were transcribed verbatim and thematically analysed deductively, with key emergent themes represented using pen profiles. Results showed that a school-based HIIT intervention can be an enjoyable form of exercise. Irrespective of attendance, similar facilitators and barriers to participating were highlighted, including benefits of participation, content of the exercise session and the intervention instructor. This study provides support for the delivery of a HIIT intervention in a school setting but highlights the importance of a flexible design and delivery to accommodate competing interests. There is a need to educate adolescents on the possible benefits of participation and to make the sessions enjoyable in order to increase their extrinsic and intrinsic motivation to sustain participation.


Endogenous testosterone density is an independent predictor of pelvic lymph node invasion in high-risk prostate cancer: results in 201 consecutive patients treated with radical prostatectomy and extended pelvic lymph node dissection.
To evaluate the influence of endogenous testosterone density (ETD) on pelvic lymph node invasion (PLNI) in high risk (HR) prostate cancer (PCa) treated with radical prostatectomy (RP) and staged with extended pelvic lymph node dissection (ePLND). ETD was evaluated as the ratio of endogenous testosterone (ET) on prostate volume (PV). HR-PCa was assessed according to the European Association of Urology (EAU) system. The association of ETD and other routinely clinical factors (BPC: percentage of biopsy positive cores; PSA: prostate specific antigen; ISUP: tumor grade system according to the International Society of Urologic Pathology; cT: tumor clinical stage) with the risk of PLNI was assessed by the logistic regression model. Overall, 201 out of 805 patients (24.9%) were classified HR and PLNI occurred in 42 subjects (20.9%). On multivariate analysis, PLNI was independently predicted by BPC (OR 1.020; 95% CI 1.006-1.035; p = 0.019), ISUP > 3 (OR 2.621; 95% CI 1.170-5.869; p = 0.019) and ETD (OR 0.932; 95% CI 0.870-0.999; p = 0.045). After categorizing continuous clinical predictors, the risk of PLNI was independently increased by ETD up to the median (OR 2.379; 95% CI 1.134-4.991; p = 0.022), BPC > 50% (OR 3.125; 95% CI 1.520-6.425; p = 0.002) as well as by ISUP > 3 (OR 2.219; 95% CI 1.031-4.776; p = 0.042). As ETD measurements decreased, patients were more likely to have PLNI. In HR disease with PLNI, the influence of PCa on ETD should be addressed by higher level studies.


Screening of women at high risk for breast cancer.
A woman may be at high risk of breast cancer because of a strong family history of breast cancer or because she carries a mutation in the BRCA1 or BRCA2 gene. The annual risk for women in this category is between 1% and 2% and the lifetime risk of breast cancer among gene carriers may approach 80%. Several recent trials have reported that the sensitivity of MRI for imaging breast cancer greatly exceeds that of conventional mammography, but no study has yet determined that annual MRI reduces breast cancer-specific mortality. Women with breast cancer and a BRCA1 mutation typically develop aggressive breast cancers and the prognosis is relatively poor for women with small node-negative breast cancers (compared to non-carriers) in particular, if chemotherapy is not given. It is hoped that annual MRI screening combined with appropriate treatment will result in decreased mortality for this and other groups of high-risk women. MRI-based screening for women at moderate risk is a topic of great interest--MRI has not yet been endorsed in moderate risk women because of the high cost of screening and because the specificity of the screening test is not yet determined in this subgroup.


Children who break dental appointments.
This was to assess factors associated with children's non-compliance with regular dental appointments. The study used demographics, oral health behaviour, oral health and use of dental services for children with a recent history of broken appointments and compared them with children who kept recall appointments. Children (n=576) recalled for routine examination in the public dental services were studied. Information regarding failed dental appointments during the previous 2 years was collected from each child's record. At examination, past history, clinical and radiographic information was recorded. The data were analysed using multiple logistic regression analysis. During the previous 2 years 15% of the children had broken at least one appointment. No significant differences were found between children with and without failed appointments regarding demographic variables (age, gender, immigrant status and medical condition) or dental health behaviours. Compared with other children, those with a history of broken appointments had more enamel disturbances, higher caries experience and higher caries activity (more new caries at the examination), and more time was needed to complete their dental treatment. They were given shorter recall intervals to the next dental examination. The results suggest that children who break appointments are caries risk patients and need special attention.


Impact of alexithymia on suicidal ideation among patients with ovarian cancer: a moderated mediation model of self-perceived burden and general self-efficacy.
Suicidal ideation (SI) and alexithymia are common psychological problems among patients with cancer. Studying how alexithymia predicts SI is helpful for its intervention and prevention strategies. The present study aimed to investigate whether self-perceived burden (SPB) mediates the impact of alexithymia on SI and if general self-efficacy moderates the associations of alexithymia with SPB and SI. To measure SI, alexithymia, SPB, and general self-efficacy, 200 patients with ovarian cancer at all stages regardless of the type of treatment completed the Chinese version of the Self-Rating Idea of Suicide Scale, Toronto Alexithymia Scale, Self-Perceived Burden Scale, and General Self-Efficacy Scale in a cross-sectional study. The PROCESS macro for SPSS v4.0 procedure was applied to perform moderated mediation analysis. SPB significantly mediated the positive impact of alexithymia on SI (a×b = 0.082, 95% confidence interval [CI]: 0.026, 0.157). General self-efficacy significantly moderated the positive association between alexithymia and SPB (β = -0.227, P < 0.001). The mediating role of SPB was gradually reduced as general self-efficacy grew (low: 0.087, 95% CI: 0.010, 0.190; medium: 0.049, 95% CI: 0.006, 0.108; high: 0.010, 95% CI: -0.014, 0.046). Thus, a moderated mediation model involving SPB and general self-efficacy for explaining how alexithymia causes SI was supported. Alexithymia could cause SI by inducing SPB among patients with ovarian cancer. General self-efficacy could attenuate the association between alexithymia and SPB. Interventions aimed at reducing SPB and enhancing general self-efficacy could reduce SI by partially preventing and attenuating the impact of alexithymia.


Preferential synthesis of diacyl and alkenylacyl ethanolamine and choline glycerophospholipids in rabbit platelet membranes.
In rabbit platelet membranes, the contents of alkenylacyl phospholipids (plasmalogen) were 56% of phosphatidylethanolamine and 3% of phosphatidylcholine. This uneven distribution of plasmalogens in each phospholipid class could be attributed to the different substrate specificity of ethanolaminephosphotransferase (EC 126.96.36.199) and cholinephosphotransferase (EC 184.108.40.206). The properties of the enzymes were studied, using endogenous diglycerides and CDP-[3H]ethanolamine or CDP-[14C]choline as substrates. The newly formed phospholipids were mainly diacyl and alkenylacyl and only rarely alkylacyl type. The ratios of the labeled alkenylacyl to diacyl type of phospholipids clearly varied with the concentrations of CDP-ethanolamine or CDP-choline. When 1, 10, and 30 microM CDP-[3H]ethanolamine were used, the labeled phospholipids contained 53, 37, and 27% of the alkenylacyl type, respectively. The apparent Km for CDP-ethanolamine to synthesize alkenylacyl and diacyl types were 2.2 and 8.1 microM. On the other hand, when 1, 10, and 30 microM CDP-[14C]choline were used, the labeled lipids contained 10, 17, and 24% alkenylacyl type, respectively. The apparent Km for CDP-choline to synthesize alkenylacyl and diacyl types were 24 and 4.3 microM. Further, the syntheses of diacyl type of phosphatidylethanolamine and the alkenylacyl type of phosphatidylcholine were markedly inhibited by unlabeled CDP-choline and CDP-ethanolamine, respectively. The two enzymes had opposite substrate specificities, and ethanolaminephosphotransferase showed a high preference to plasmalogen synthesis, especially in the presence of CDP-choline.


Dependence of the torsional rigidity of DNA on base composition.
The Escherichia coli phage 434 repressor binds as a dimer to the operator of the DNA helix. Although the centre of the operator is not in contact with protein, the repressor binding affinity can be reduced at least 50-fold by changing the sequence there: operators with A.T base pairs near their centre bind the repressor more strongly than do operators with G.C base pairs at the same positions. To explain these observations, it has been proposed that the base composition at the centre of the operator affects the affinity of the operator for repressor by altering the ease with which operator DNA can undergo the torsional deformation necessary for complex formation. In this model, the variation in binding affinity would require the torsion constant to have specific values and to change in a sequence-dependent manner. We have now measured torsion constants for DNAs with widely different base compositions. Our results indicate that the torsion constants depend only slightly on the overall composition, and firmly delimit the range of values for each. Even the upper-limit values are much too small to account for the observed changes in affinity of the 434 repressor. These results rule out simple models that rely on substantial generic differences in torsion constant between A.T-rich sequences and G.C-rich sequences, although they do not rule out the possibility of particular sequences having abnormal torsion constants.


3-[3-(Pyridin-3-yl)-1,2,4-oxadiazol-5-yl]propanoic acid.
In the title compound, C(10)H(9)N(3)O(3), the benzene ring is almost coplanar with the heterocyclic ring, making a dihedral angle of 11.3 (1)°. The plane of the carboxyl group is rotated by 8.4 (2)° with respect to the 1,2,4-oxadiazole ring plane. The aliphatic chain exhibits an extended conformation. In the crystal, mol-ecules are liked through inter-molecular O-H⋯N bonds, forming a chain structure along the c axis.


Characterization of the transcriptional expression of Notch-1 signaling pathway members, Deltex and HES-1, in developing mouse thymocytes.
The Notch transmembrane protein is involved in a broad range of different developmental pathways in vertebrates and invertebrates. Targeted thymocyte expression of the Notch-1 intracellular domain has been shown to affect lineage commitment decisions such as those involving T cell vs. B cell, thymocyte alpha beta vs. gamma delta TCR, as well as CD4 vs. CD8 thymocyte commitment. In this paper, we quantitatively characterize thymocyte RNA expression of two purported transcriptional markers of Notch-1 signaling activity, Deltex and HES-1. Using a semiquantitative RTPCR approach, we show that both Deltex and HES-1 transcriptional levels are developmentally regulated as thymocytes mature from the earliest CD4/CD8 double negative thymocyte stage, through the intermediate CD4/CD8 double positive stage, and finally to the mature CD4 or CD8 single positive stage. Deltex and HES-1, despite both being transcriptional markers of Notch-1 activity, express different patterns of transcriptional activity among the thymocyte subsets. Neither treatment with combined (alpha CD3)/(alpha CD28) antibodies nor the combination of the phorbol ester PMA and calcium ionophore ionomycin affects expression of Deltex in immature thymocytes; however, PMA/ionomycin treatment does downregulate expression of HES-1, an affect mostly mediated by ionomycin. Finally, a difference in HES-1 expression is seen between CD4/CD8 double positive thymocytes isolated from wild-type vs. MHC class I/II deficient mice, suggesting that Notch-1 activity is modulated during in vivo TCR/MHC-ligand selection events.


Specific modulation of brain stimulation reward by haloperidol.
Low doses of haloperidol (3--18 micrograms/kg) caused dose related increases in reinforcing thresholds for self-stimulation to the medial forebrain bundle in rats. These effects, which were demonstrated completely independent of performance variables, indicate a direct modulation of central reinforcement processes by this drug, at doses which have highly selective action on dopaminergic neurotransmission.


Strain differences in rats with respect to speed of conflict resolution.
Speed of conflict resolution was studied in a conditioned punishment paradigm in a Skinner box and a straight runway. In both experimental situations speed of conflict resolution was defined as the latency to gain food during an approach-avoidance conflict. In the Skinner box Tryon Maze Bright rats were faster in speed of conflict resolution than Tryon Maze Dull rats, and Roman Low Avoidance rats were faster than Roman High Avoidance rats. In the runway situation, Wistar Kyoto rats were faster in solving the conflict than randomly bred Wistar Wu rats and Brown Norway rats were faster than Wistar Wu rats. Differences between the strains in speed of conflict resolution could not be consistently explained from strain differences in approach or avoidance behavior, measured separately. It is, therefore, suggested that speed of conflict resolution is a unique parameter.


Immediate reinfection with Omicron variant after clearance of a previous SARS-CoV-2 infection.
SARS-CoV-2 Omicron variant is spreading worldwide, causing unprecedented epidemic peaks due to its transmissibility and immune evasion. We searched in the archive of the Regional Microbiology Laboratory (Umbria, Italy) for immediate reinfection (i.e. infection occurring 25-60 days from primary infection) among 454,764 RT-PCR tests from 261,217 individuals. Lineage heterogeneity was assessed by S gene target failure phenomenon or whole genome sequencing. We found that BA.1 Omicron variant may cause immediate reinfection of patients just recovered from Delta infection. Immediate reinfection was not observed for any other combination of variants, including Delta over Alpha variant and BA.2 over BA.1 Omicron lineage.


Heterotopic bone formation in abdominal incisions.
1. Heterotopic bone formation in abdominal scars is not as rare as the paucity of case reports in the literature would indicate. 2. Females comprised 21 percent of our patients. 3. The average age was fifty-five years. 4. The probable cause of this bone formation is injury to the xiphoid process above or the pubis below, with liberation of bone-forming cells into the wound. 5. Heterotopic bone usually remains permanently in the wound, but it can be absorbed and disappear, as was noted in one of our patients. 6. The bone should only be excised if it causes enough discomfort to warrant its removal. Careful removal should avoid recurrence. 7. In operations for intra-abdominal malignant lesions, bone formation should not be mistaken for recurrent malignant disease in the abdominal wall.


Presence and distribution of persistent toxic substances in sediments and marine organisms of Potter Cove, Antarctica.
Levels of butyltin compounds, polychlorinated biphenyls, and heavy metals were analyzed in marine sediments and organisms (Notothenia coriiceps, Laternula elliptica, and Nacella concinna), each of which has a different feeding strategy, in Potter Cove, Antarctica. PCBs were lower than detection limits in all samples. Only butyltin compounds were detected in a restricted area near the scientific station. Chromium, copper, magnesium, lead (Pb), and zinc had similar behavior in the cove, probably because they are regulated by similar process and conditions. However, Pb levels in some sites of the cove seem to be related to human activities in the area. Cadmium levels were relatively low, with the highest values found close to the shoreline, which is probably influenced by seasonal streams draining waters from Potter Peninsula. Results showed that despite the fact that Jubany Station has been operating for > 50 years, surface sediment and biota from Potter Cove do not exhibit levels of pollutants representing environmental concern.


The characterization of SV40-transformed cell lines derived from mouse teratocarcinoma: growth properties and differentiated characteristics.
Mouse teratocarcinoma cells derived from embryoid bodies of 129SVsl mice were cultured in vitro to permit their differentiation. These cells were then infected with simiam virus 40 (SV40) and 31 cloned cell lines (SVTER) were derived from these cultures. All 31 SVTER cell lines contained the SV40 tumor (T) antigen and grew as permanent lines in culture. Mock-infected embryoid body cultures did not give rise to permanent cell lines. The morphology of each SVTER cell line was distinct and did not change during successive subclonings. The growth properties and tumorigenic potential of all 31 SVTER cell lines were investigated. None of these lines produced tumors in 129SVsl mice. Each cell line was tested for its ability to (1) grow in medium containing 1% serum, (2) plate on cell monolayer, and (3) form clones in methocel suspension. Only three of the SVTER cell lines were transformed with respect to all three of these criteria. Most of these cell lines were minimal transformants. The SVTER cell lines were tested for creatine phospholinase (CPK), an enzyme activity chracteristic of mouse brain and muscle tissue, and the protease, plasminogen activator (PA) which is found in embryoid bodies and several differentiated cell types. Some of the SVTER cell lines contained high levels of CPK, while others had high levels of PA and a third group of cells contained neither enzyme activity. No SVTER cell line was found with high levels of both these enzyme activities. This result suggests that mutually exclusive sets of genes are expressed in these cells as might be expected from the distinct tissue distribution of the two enzyme activities studied. These SVTER cell lines may be useful in reconstructing developmental pathways of differentiating teratomas in vitro.


Early donor management increases the retrieval rate of lungs for transplantation.
Lung transplantation activity is frustrated by donor lung availability. We sought to examine the effect of active donor management and hormone administration on pulmonary function and yield in cadaveric heart-beating potential lung donors. We studied 182 potential lung donors (arterial oxygen tension [PaO2]/fractional inspired oxygen [FIO2] ratio > or = 230). From this group, 60 patients (120 lungs) were allocated, within a randomized trial, to receive methylprednisolone (1 g), triiodothyronine (0.8 microg/kg bolus and 0.113 microg/kg/h infusion), both methylprednisolone and triiodothyronine, or placebo as soon as feasible after consent and initial assessment. Trial donors underwent protocol-guided optimization of ventilation and hemodynamics, lung water assessment, and bronchoscopy. Function was assessed by PaO2/FIO2 ratio, extravascular lung water index (EVLWI), and pulmonary vascular resistance (PVR). A nontrial group of 122 donors (244 lungs) received similar management without bronchoscopy, pulmonary artery flotation catheter monitoring, or lung water assessment. Within the trial, management commenced within a median of 2 hours (interquartile range, 0.5 to 3.5 hours) of consent and continued for an average of 6.9 +/- 1.2 hours. The PaO2/FIO2 ratio deteriorated (p = 0.028) from 397 +/- 78 (95% CL, 376 to 417) to 359 +/- 126 (95% CL, 328 to 390) and EVLWI from 9.7 +/- 4.5 mL/kg (95% CL, 8.6 to 10.9 mL/kg) to 10.8 +/- 5.2 mL/kg (95% CL, 9.4 to 12.2 mL/kg; p = 0.009). PVR remained unchanged (p = 0.28). At end management, 48 of 120 trial lungs (40%) were transplanted versus 66 of 244 nontrial lungs (27%; p = 0.016). Neither methylprednisolone and triiodothyronine nor T3 increased lung yield or affected PaO2/FIO2 or EVLWI; however, methylprednisolone attenuated the increase in EVLWI (p = 0.009). Early active management of lung donors increases yield. Steroid administration reduces progressive lung water accumulation.


Intermediates of copper(I)-catalyzed C-S cross coupling of thiophenol with aryl halide by in situ ESI-MS study.
Complexes [Cu(SPh)(2)](-), [Cu(SPh)I](-) and K[Cu(SPh)(2)(Ph)](+) were observed by in situ electrospray ionization mass spectrometry (ESI-MS) analysis of the copper(i)-catalyzed C-S coupling reaction under catalytic reaction conditions indicating that they are intermediates in the reaction. A catalytic cycle was proposed based on these observations.


Effects of intrusive forces upon the microvasculature of the dental pulp.
This in vivo study has demonstrated in rats that the nutritional blood flow of the pulp may be compromised after application of an intrusive orthodontic force. The results of this study and the findings of other investigators suggest that an in depth study analyzing the relationship between pulpal viability and orthodontic tooth movement may be indicated.


Disparities in Survival and Comorbidity Burden Between Asian and Native Hawaiian and Other Pacific Islander Patients With Cancer.
Improper aggregation of Native Hawaiian and other Pacific Islander individuals with Asian individuals can mask Native Hawaiian and other Pacific Islander patient outcomes. A comprehensive assessment of cancer disparities comparing Asian with Native Hawaiian and other Pacific Islander populations is lacking. To compare comorbidity burden and survival among East Asian, Native Hawaiian and other Pacific Islander, South Asian, and Southeast Asian individuals with non-Hispanic White individuals with cancer. This retrospective cohort study used a national hospital-based oncology database enriched with Native Hawaiian and other Pacific Islander and Asian populations. Asian, Native Hawaiian and other Pacific Islander, and White individuals diagnosed with the most common cancers who received treatment from January 1, 2004, to December 31, 2017, were included. Patients younger than 18 years, without pathologic confirmation of cancer, or with metastatic disease were excluded. Data were analyzed from January to May 2022. The primary end points were comorbidity burden by Charlson-Deyo Comorbidity Index and overall survival (OS). In total, 5 955 550 patients were assessed, including 60 047 East Asian, 11 512 Native Hawaiian and other Pacific Islander, 25 966 South Asian, 42 815 Southeast Asian, and 5 815 210 White patients. The median (IQR) age was 65 (56-74) years, median (IQR) follow-up was 58 (30-96) months, and 3 384 960 (57%) were women. Patients were predominantly from metropolitan areas (4 834 457 patients [84%]) and the Southern United States (1 987 506 patients [34%]), with above median education (3 576 460 patients [65%]), and without comorbidities (4 603 386 patients [77%]). Cancers included breast (1 895 351 patients [32%]), prostate (948 583 patients [16%]), kidney or bladder (689 187 patients [12%]), lung (665 622 patients [11%]), colorectal (659 165 patients [11%]), melanoma (459 904 patients [8%]), endometrial (307 401 patients [5%]), lymphoma (245 003 patients [4%]), and oral cavity (85 334 patients [1%]) malignant neoplasms. Native Hawaiian and other Pacific Islander patients had the highest comorbidity burden (adjusted odds ratio [aOR], 1.70; 95% CI, 1.47-1.94) compared with Asian and White groups. Asian patients had superior OS compared with White patients for most cancers; only Southeast Asian patients with lymphoma had inferior survival (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.16-1.37). In contrast, Native Hawaiian and other Pacific Islander patients demonstrated inferior OS compared with Asian and White patients for oral cavity cancer (aHR, 1.56; 95% CI, 1.14-2.13), lymphoma (aHR, 1.35; 95% CI, 1.11-1.63), endometrial cancer (aHR, 1.30; 95% CI, 1.12-1.50), prostate cancer (aHR, 1.29; 95% CI, 1.14-1.46), and breast cancer (aHR, 1.09; 95% CI, 1.00-1.18). No cancers among Native Hawaiian and other Pacific Islander patients had superior OS compared with White patients. In this cohort study, compared with White patients with the most common cancers, Asian patients had superior survival outcomes while Native Hawaiian and other Pacific Islander patients had inferior survival outcomes. Native Hawaiian and other Pacific Islander patients had significantly greater comorbidity burden compared with Asian and White patients, but this alone did not explain the poor survival outcomes. These results support the disaggregation of these groups in cancer studies.


General practitioners' continuation and acceptance of medication changes at sectorial transitions of geriatric patients - a qualitative interview study.
Follow-up in general practice on medication initiated during hospitalisation is often perceived to be inadequate, which leads to unintended drug interaction and over- or underdosage of medication. Little is known about General Practitioners (GPs') views on medication changes during the transition from hospital to primary care. We conducted a qualitative interview study to understand GPs' views on the medication changes made for their patients by hospital physicians in a geriatric ward and the GPs' actions after discharge. Qualitative semi-structured interviews comprising ten GPs from general practices in the Region of Southern Denmark, using a phenomenological approach. The GPs were selected strategically based on the principle of maximum variation. The analysis process was a cross-sectional analysis based on a phenomenological analysis. The GPs identified many reasons for the lack of medication continuation, including miscommunication between hospital doctors and GPs and delayed discharge letters. Several factors were involved, including patients not taking responsibility for their medication, no structure for follow-up visits to their GPs and for the renewal of their prescriptions. The main reason for the poor continuity of medication changes for geriatric patients at sector transition was neither the GPs' deliberate actions of removing the patients' medications, nor the patients' lack of compliance or of willingness to take the medication. It is largely due to procedural errors in the follow-up on the patient after discharge, due to the lack of a structured process and due to miscommunication between the primary sector and the hospital.


Nabiximols oromucosal spray in patients with multiple sclerosis-related bladder dysfunction: A prospective study.
Spasticity and urinary disturbances can profoundly impact the daily lives of persons with multiple sclerosis (pwMS). Cannabis has been associated with improvement in sphincteric disturbances. To our knowledge, few studies have evaluated the effect of nabiximols oromucosal spray (Sativex®) on urinary disturbances by instrumental methods. This longitudinal study was conducted to assess the effect of nabiximols oromucosal spray on urinary disturbances by clinical and urodynamic evaluation in pwMS. Neurological, spasticity, and quality of life (QoL) assessments were performed before (T0), and at one (T1) and six (T6) months after the start of nabiximols treatment. At these same time points, patients were assessed for urinary disturbances by the International Prostatic Symptoms Score (IPSS) and a urodynamic test evaluating maximum detrusor pressure (Pdet), bladder filling capacity (CCmax), uninhibited detrusor contractions (UDC), bladder volume at first desire (BVFD), post-void residual volume (PVR) and voluntary abdominal pressure (PA). Of 31 pwMS enrolled in the study, 25 reached T1 and 18 reached T6. Mean IPSS total score, its subscores, and IPSS QoL decreased significantly from T0 to T6 (p = 0.000), with no differences according to sex, age, MS type, disease duration and disability at baseline. Pdet improved significantly from T0 to T6 (p = 0.0171), and CCmax changed only marginally (p = 0.0494); results were similar in patient subgroups naïve to or previously exposed to urological treatment. All patients with overactive bladder showed improvement in their urodynamic assessment based on significant reduction of Pdet (p = 0.0138). In patients with mainly hypotonic bladder, mean Pdet decreased from T0 to T6 without reaching statistical significance; most urodynamic parameters showed a trend to improve. Mean numerical scale scores for MS spasticity, and for spasms, pain and tremors, decreased significantly from T0 to T6. The mean 'physical health composite' score of the MS Quality of Life-54 questionnaire increased significantly from T0 to T6 (p = 0.0126). Our data suggest that nabiximols has an appreciable effect on ameliorating subjective perception of urinary disturbances and appears to have a positive effect on objective urodynamic parameters, particularly in patients with hyperactive bladder.


Prospective evaluation of watchful waiting for early-stage lung cancer with ground-glass opacity: a single-arm confirmatory multicenter study: Japan Clinical Oncology Group study JCOG1906 (EVERGREEN study).
Among early-stage lung cancers that show ground-glass nodules on chest computed tomography, the lung cancer surgical study group of the Japan Clinical Oncology Group previously reported that nodules of ≤2 cm with a consolidation/tumor ratio of ≤0.25 were considered radiologically non-invasive cancers with a low risk of metastasis. However, there is no consensus based on high-quality evidence about the optimal timing of surgical intervention for radiologically non-invasive cancers. In June 2020, we launched a multi-institutional, single-arm confirmatory trial to evaluate the efficacy and safety of watchful waiting for patients with radiologically non-invasive lung cancer. It is planned that a total of 720 patients will be enrolled from 49 institutes over a 5-year period. The primary endpoint is 10-year overall survival (OS). The secondary endpoints are 5-year OS, operation-free survival, proportion of extensive lung resection, proportion of unresectable progression, lung cancer-specific survival and adverse events.


[Fermentation equipment of the USSR Academy of Sciences Institute of Microbiology for continuous cultivation of microorganisms].
A fermentation apparatus has been constructed in the Institute of Microbiology of the USSR Academy of Sciences. The apparatus permits to cultivate microorganisms both under periodic and continuous conditions with automatic regulation of pH, Eh, temperature, measurement of pO2, etc.


Expression of the CA1 determinant by carcinomas and by non-malignant epithelial cells in oral lesions.
The expression of the Ca antigen was investigated in 5 groups of oral lesions comprising 7 squamous cell carcinomas, 2 pre-invasive carcinomas, 7 lesions of types believed to predispose to carcinoma, 19 lesions of types that do not predispose to carcinoma and 5 biopsies of normal oral mucosa. Using an indirect immunoperoxidase method, the neoplastic epithelium reacted positively with the Ca1 antibody in only 4 out of 7 oral squamous cell carcinomas and the reaction varied between the specimens as to the intensity and number of positively stained cells. Several benign oral lesions specifically bound the Ca1 antibody in areas of epithelium showing infiltration with inflammatory cells. These lesions comprised 5 fibrous epulides, 1 pyogenic granuloma, 1 denture-induced hyperplasia and 1 non-diagnostic ulcer. We conclude that the Ca1 antibody is not sufficiently specific for the carcinoma to be of value in the diagnosis of malignant and premalignant lesions of the oral mucosa.


Protective effect of Dunaliella salina (Volvocales, Chlorophyta) against experimentally induced fibrosarcoma on wistar rats.
The beta-carotene-yielding microalga, Dunaliella salina (Dunal) Teod. maintained in De Walne's medium was harvested and lyophilized. Fibrosarcoma was induced in rats by 20-methylcholanthrene. 0.5 g and 1.0 g of lyophilized D. salina powder was administered to the rats orally through carboxy methyl cellulose. Cisplatin was administered along with vitamin E to compare the protective effect of D. salina against fibrosarcoma. Administration of D. salina decreased the levels of cholesterol and lactate dehydrogenase as well as the activities of catalase, superoxide dismutase, serum aspartate aminotransaminase, serum alanine aminotransferase, when compared to control. A significant reduction in the levels of hepatic and renal RNA and DNA was observed in the sarcoma rats when treated with D. salina powder. Histopathological studies of tumor tissues showed regenerative and regressive changes. beta-carotene globules isolated from the powder of Dunaliella salina confirmed the presence of 9-cis-beta-carotene and all-trans-beta-carotene.


Should optimal timing between two intrauterine transfusions be based on estimated daily decrease of hemoglobin or on measurement of fetal middle cerebral artery peak systolic velocity?
To best predict the recurrence of fetal anemia after intrauterine transfusion (IUT), the measurement of middle cerebral artery peak systolic velocity (PSV) and the estimation of hemoglobin (Hb) daily decrease are compared. A retrospective study including 38 patients who had at least two IUTs in a context of red blood cell alloimmunization was conducted. PSV values before first, second, and third IUTs were collected and expected Hb level was calculated according to various Hb daily decrease formulas as proposed in the literature. Comparison of PSV receiver operating characteristic curves with the various Hb levels did not find any significant difference between first and second IUTs. On the other hand, we found a significant difference between the second and third IUTs, with better prediction of fetal anemia through Hb decrease calculation, whatever the formula. Between the second and third IUTs, no formula was significantly better than the others. The timing of a second transfusion can be difficult to determine with certainty, but PSV can give an accurate assessment of when to resample the fetus with probably a higher recommended threshold for the diagnosis of fetal anemia. Subsequent to a second transfusion, the intertransfusion interval should be based on estimated Hb decrease rather than PSV thresholds, whatever the chosen formula proposed in the literature. Larger numbers are needed to definitely make this recommendation and it will be interesting to evaluate correlation between different antibodies.