Low-dose ARA-C fails to enhance differentiation of leukaemic cells.
Nine patients with acute myelogenous leukaemia were treated with low-dose ARA-C (10 mg/m2, q 12h) for a planned 21 d. Complete remission was attained in only one patient (11.1%). Definite cytoreductive effect was seen in four additional patients. There was one treatment-related death. Haematologic toxicity occurred in all nine patients with sever thrombocytopenia most prominent. Severe hepatotoxicity precluded further ARA-C treatment in one patient. Because of toxicity only two patients were able to complete their scheduled 3 week courses of low-dose ARA-C. No evidence of ARA-C induced differentiation of leukaemic cells was noted on follow-up bone marrow examination during or shortly after the treatment course. The utility and indication for low-dose ARA-C therapy of AML remains to be determined.


Viruses of hyperthermophilic Crenarchaea.
Since the discovery of the Archaea--the third domain of life--by Woese and colleagues in 1977, the subsequent developments in molecular and cell biology, and also genomics, have strongly reinforced the view that archaea and eukarya co-evolved, separately from bacteria, over a long time. However, when one examines the archaeal viruses, the picture appears complex. Most viruses that are known to infect members of the kingdom Euryarchaeota resemble bacterial viruses, whereas those associated with the kingdom Crenarchaeota show little resemblance to either bacterial or eukaryal viruses. This review summarizes our current knowledge of this group of exceptional and highly diverse archaeal viruses.


Eating disorder behaviors and attitudes in Japanese adolescent girls and boys in high schools.
To investigate eating disorder behaviors and attitudes in adolescents, we administered the eating disorder examination questionnaire (EDE-Q) to Japanese adolescent girls and boys. The EDE-Q global scores in Japanese girls and boys, respectively, were significantly lower than those in girls and boys in previous studies. Objective binge eating episodes and extreme dietary restriction were the common behaviors, whereas self-induced vomiting and the misuse of laxatives were uncommon. Differences in the EDE-Q data between Japanese adolescents and adolescents in previous studies from Western countries suggest that there may be certain cultural differences in eating disorder psychopathology in adolescents.


Wellbeing while waiting evaluating social prescribing in CAMHS: study protocol for a hybrid type II implementation-effectiveness study.
Social prescribing is a mechanism of connecting patients with non-medical forms of support within the community and has been shown to improve mental health and wellbeing in adult populations. In the last few years, it has been used in child and youth settings with promising results. Currently, pathways are being developed for social prescribing in Child and Adolescent Mental Health Services (CAMHS) to support children and young people on treatment waiting lists. The Wellbeing While Waiting study will evaluate whether social prescribing benefits the mental health and wellbeing of children and young people. This study utilises an observational, hybrid type II implementation-effectiveness design. Up to ten CAMHS who are developing social prescribing pathways as part of a programme run across England with support from the Social Prescribing Youth Network will participate. Outcomes for children and young people receiving social prescribing whilst on CAMHS waiting lists will be compared to a control group recruited prior to the pathway roll-out. Questionnaire data will be collected at baseline, 3 months and 6 months. Primary outcomes for children and young people are mental health symptoms (including anxiety, depression, stress, emotional and behavioural difficulties). Secondary outcomes include: loneliness, resilience, happiness, whether life is worthwhile, life satisfaction, and service use. An implementation strand using questionnaires and interviews will explore the acceptability, feasibility, and suitability of the pathway, potential mechanisms of action and their moderating effects on the outcomes of interest, as well as the perceived impact of social prescribing. Questionnaire data will be analysed mainly using difference-in-differences or controlled interrupted time series analysis. Interview data will be analysed using reflexive thematic analysis. The Wellbeing While Waiting study will provide the first rigorous evidence of the impact of social prescribing for children and young people on waiting lists for mental health treatment. Findings will help inform the prioritisation, commissioning, and running of social prescribing in other CAMHS. To maximise impact, findings will be available on the study website ( https://sbbresearch.org ) and disseminated via national and international networks. N/A.


Renewable energy in the United States: is there enough land?
A review of studies of biomass potential in the United States finds a wide variation in the estimates. A number of specific policy-relevant questions about the potential of biofuels in the United States are answered. A recently published global analysis of the potential conflict between land needed for bioenergy and land needed for food is extended to the situation in the United States. A renewable energy supply scenario, capable of meeting the 2001 US energy demand, indicates that there is enough land to support a renewable energy system but that the utilization of biomass would be limited by its land requirement.


Phase I dose-escalating study of panobinostat (LBH589) administered intravenously to Japanese patients with advanced solid tumors.
Panobinostat (LBH589) is a potent pan-histone deacetylase inhibitor. As a result of promising preclinical data, Phase I and II clinical trials of intravenous and oral panobinostat have been conducted in patients with a wide variety of hematologic and solid tumors. This is the first report of a phase I study to evaluate intravenous panobinostat given on days 1 and 8 of a 21-day cycle in patients with solid tumors. The primary objective was to characterize the safety and tolerability of panobinostat by evaluating the occurrence of dose-limiting toxicity (DLT) and determining the maximum tolerated dose (MTD) in Japanese patients with advanced solid tumors. Secondary objectives included characterizing the pharmacokinetics and assessing antitumor activity. Fourteen patients were assigned to three dose levels (Cohort 1: 10 mg/m(2) [three patients], Cohort 2: 15 mg/m(2) [three patients], Cohort 3: 20 mg/m(2) [eight patients]), according to a standard "3 + 3" design. One patient who received 20 mg/m(2) had a DLT (grade 3 elevation of γ-glutamyl transpeptidase for >7 days). Thrombocytopenia was observed in all patients (grade 3 or 4 in 8), the severity of which was dependent on the dose and platelet count at baseline. The thrombocytopenia rapidly resolved within 8 days. Plasma panobinostat levels increased dose dependently, without clinically significant drug accumulation. Stable disease for ≥4 months was observed in six patients; however, there were no complete or partial responses. It is feasible to conclude that 20 mg/m(2) was the MTD and recommend as the starting dose for phase II clinical trials.


[Fireworks injuries of the eye: an overview of current diagnostic and treatment options].
Fireworks can cause very different eye injuries. The injury patterns range from spontaneously healing conjunctival and corneal lesions up to a burst eyeball with very severe injuries in the posterior ocular section and traumatic enucleation. The precise initial diagnosis in an emergency situation can be a challenge for the ophthalmologist. Children and adolescents are often affected. The patient history with respect to the circumstances of the accident is particularly important to be able to estimate the extent of the injury and to initiate a conservative or, if necessary, emergency operative treatment. This article provides an overview of typical injury patterns and advice for the diagnostics, treatment and complication management.


Ultra high dose rate (35 Gy/sec) radiation does not spare the normal tissue in cardiac and splenic models of lymphopenia and gastrointestinal syndrome.
Recent reports have shown that very high dose rate radiation (35-100 Gy/second) referred to as FLASH tends to spare the normal tissues while retaining the therapeutic effect on tumor. We undertook a series of experiments to assess if ultra-high dose rate of 35 Gy/second can spare the immune system in models of radiation induced lymphopenia. We compared the tumoricidal potency of ultra-high dose rate and conventional dose rate radiation using a classical clonogenic assay in murine pancreatic cancer cell lines. We also assessed the lymphocyte sparing potential in cardiac and splenic irradiation models of lymphopenia and assessed the severity of radiation-induced gastrointestinal toxicity triggered by the two dose rate regimes in vivo. Ultra-high dose rate irradiation more potently induces clonogenic cell death than conventional dose rate irradiation with a dose enhancement factor at 10% survival (DEF10) of 1.310 and 1.365 for KPC and Panc02 cell lines, respectively. Ultra-high dose rate was equally potent in depleting CD3, CD4, CD8, and CD19 lymphocyte populations in both cardiac and splenic irradiation models of lymphopenia. Radiation-induced gastrointestinal toxicity was more pronounced and mouse survival (7 days vs. 15 days, p = 0.0001) was inferior in the ultra-high dose rate arm compared to conventional dose rate arm. These results suggest that, contrary to published data in other models of radiation-induced acute and chronic toxicity, dose rates of 35 Gy/s do not protect mice from the detrimental side effects of irradiation in our models of cardiac and splenic radiation-induced lymphopenia or gastrointestinal mucosal injury.


Characteristics, work environments, and rates of burnout and job dissatisfaction among registered nurses in primary care.
Although more people than ever are seeking primary care, the ratio of primary care providers to the population continues to rapidly decline. As such, registered nurses (RNs) are taking on increasingly central roles in primary care delivery. Yet little is known about their characteristics, their work environments, and the extent to which they experience poor job outcomes such as nurse burnout. The purpose of this study was to examine the characteristics of the primary care RN workforce and analyze the association of the nurse work environment with job outcomes in primary care. Cross-sectional analysis of survey data representing N = 463 RNs who worked in 398 primary care practices, including primary care offices, community clinics, retail/urgent care clinics, and nurse-managed clinics. Survey questions included measures of the nurse work environment and levels of burnout, job dissatisfaction, and intent to leave. Approximately one-third of primary care RNs were burnt out and dissatisfied with their jobs, with the highest risk of these outcomes among RNs in community clinics. Community clinic RNs were also significantly more likely to be Black or Hispanic/Latino, hold a Bachelor of Science in Nursing, and speak English as a second language (all p < .01). Across all settings, better nurse work environments were significantly associated with lower levels of burnout and job dissatisfaction (both p < .01). Primary care practices must be equipped to support their RN workforce. Adequate nursing resources are especially needed in community clinics, as patients receiving primary care in these settings frequently face structural inequities.


Effectiveness and moderators of cancer patient-caregiver dyad interventions in improving psychological distress: A systematic review and meta-analysis.
As patients and family caregivers are increasingly viewed as a dyadic whole, growing studies have emerged that identify ways to improve the two parties' emotional distress. However, the specific effectiveness, quality, and optimal intervention details of these studies are unclear. Our objective is to synthesize the effectiveness of existing dyadic interventions for improving the psychological distress of cancer patient-caregiver dyads and identify potential moderators that influence intervention effectiveness. PubMed, Cochrane Library, Web of Science, CINHAL, Embase, and Clinical Trials were searched to identify all randomized controlled trials from inception until June 2021. Two reviewers performed the process independently. The Cochrane Risk of Bias tool was used for quality assessment. We calculated effect sizes (Hedges' adjusted g) by standard mean difference. Potential moderators influencing the intervention effects were explored. We included 28 articles, of which 12 were available for meta-analysis. In total, 4784 participants were included, who were primarily middle-aged (M = 58 years old), with the highest proportion reporting a diagnosis of "mixed cancer" (30%). Patients' anxiety (g = -0.31; 95% CI: -0.51 to -0.12; P = 0.001; I 2 = 17%) and cancer-related distress (g = -0.32; 95% CI: -0.46 to -0.18; P < 0.0001; I 2 = 0%) were statistically significantly improved from baseline to post-intervention. Interventionist, delivery type, duration, and frequency were potential moderators for psychosocial interventions on negative emotions. Face-to-face, relatively shorter interventions led by psychologists in moderator analysis seem to have better performance. Cancer dyad-based interventions were efficacious in improving the emotional distress of both parties in the dyad, but the effect was more apparent in patients than in family caregivers. However, the long-term effects were modest for both groups.


In elite athletes with meniscal injuries, always repair the lateral, think about the medial! A systematic review.
This study aimed to evaluate and compare the time required to return to sports (RTS) after surgery, the rate of revision surgery and the time required for RTS after revision surgery in elite athletes undergoing meniscal repair or partial meniscectomy, particularly analysing the difference between medial and lateral menisci. It was hypothesised that both procedures would entail similar, high rates of RTS, with the lateral meniscus exhibiting higher potential healing postprocedure compared to the medial meniscus. A systematic review was conducted based on the PRISMA guidelines. Quality assessment of the systematic review was performed using the AMSTAR-2 checklist. The following search terms were browsed in the title, abstract and keyword fields: 'meniscus' or 'meniscal' AND 'tear,' 'injury' or 'lesion' AND 'professional,' 'elite' or 'high-level' AND 'athletes,' 'sports,' 'sportsman,' 'soccer,' 'basketball,' 'football' or 'handball'. The resulting measures extracted from the studies were the rate of RTS, level of RTS, complications, revision surgery and subsequent RTS, Tegner, International Knee Documentation Committee (IKDC) and Visual Analogue Scale (VAS). In this study, the cohort consisted of 421 patients [415 (98.6%) men and 6 (1.4%) women] with a mean age of 23.0 ± 3.0 years. All patients were elite athletes in wrestling, baseball, soccer, rugby or handball. While 327 (77.7%) patients received partial meniscectomy at a mean age of 23.3 ± 2.6 years, 94 (22.3%) patients received meniscal repair at a mean age of 22.1 ± 4.0 years. After partial meniscectomy, 277 patients (84.7%) returned to their competitive sports activity and 256 (78.3%) returned to their pre-injury activity levels. A total of 12 (3.7%) patients required revision surgery because of persistent pain [5 (1.5%) patients], chondrolysis [2 (0.7%) patients] or both chondrolysis and lateral instability [5 (1.5%) patients]. Ten (83.3%) of the twelve patients had involvement of the lateral meniscus, whereas the location of injury was not specified in the remaining two patients. After revision surgery, all patients (100%) resumed sports activity. However, after meniscal repair, 80 (85.1%) athletes returned to their competitive sports activity and 71 (75.5%) returned to their pre-injury activity levels. A total of 16 (17.0%) patients required partial meniscectomy in cases of persistent pain or suture failure. Of these, 4 (25%) patients involved lateral and medial menisci each and 8 (50%) patients were not specified. After revision surgery, more than 80.0% of the patients (13) resumed sports activity. In elite athletes with isolated meniscal injury, partial meniscectomy and meniscal suture exhibited similar rates of RTS and return to pre-injury levels. Nonetheless, athletes required more time for RTS after meniscal repair and exhibited an increased rate of revision surgery associated with a reduced rate of RTS after the subsequent surgery. For lateral meniscus tears, meniscectomy was associated with a high rate of revision surgery and risk of chondrolysis, whereas partial medial meniscectomy allowed for rapid RTS but with the potential risk of developing knee osteoarthritis over the years. The findings of this systematic review suggested a suture on the lateral meniscus in elite athletes because of the high healing potential after the procedure, the reduced risk of developing chondrolysis and the high risk of revision surgery after partial meniscectomy. Furthermore, it is important to evaluate several factors while dealing with the medial meniscus. If rapid RTS activity is needed, a hyperselective meniscectomy is recommended; otherwise, a meniscal suture is recommended to avoid accelerated osteoarthritis. Level IV. PROSPERO-CRD42022351979 ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=351979 ).


Oculomotor and vestibular findings in autosomal recessive spastic ataxia of Charlevoix-Saguenay.
Electronystagmographic recordings were made of oculomotor and vestibular function in 11 patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay. All had horizontal gaze nystagmus, marked impairment of smooth ocular pursuit and optokinetic nystagmus, and defective fixation suppression of caloric nystagmus. Many had saccadic dysmetria, but saccade velocity was probably unaffected. Abnormalities pointing to brainstem disturbance were sparse. The findings are thought to indicate mainly diffuse cerebellar disease, with particular involvement of vermis and vestibulo-cerebellum.


Correlation Between Immune-Related Adverse Events and Prognosis in Hepatocellular Carcinoma Patients Treated With Immune Checkpoint Inhibitors.
Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) were associated with clinical benefit in cancer patients of melanoma, a lung cancer. In the present study, we investigated the correlation between irAE and ICI efficacy in hepatocellular carcinoma (HCC) patients. We divided the HCC patients who received the anti-PD-1 antibody into two groups as irAE group and non-irAE group according to the National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.03. The treatment efficacy of ICIs was evaluated with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Of the 65 HCC patients who received the anti-PD-1 antibody (monotherapy or combined with targeted medicine), median PFS in the irAE group was superior to that in the non-irAE group (302 days vs. 148 days, p = 0.004). Median OS in the irAE group was also better than that in the non-irAE group (374 days vs. 279 days, p = 0.038). Although the statistical difference for DCR in the irAE group and non-irAE group was not reached, the DCR of the irAE displayed a trend better than that of the non-irAE group (41.20% vs. 20.80%, p = 0.118). Multivariate analysis also demonstrated that the non-irAE group (HR = 6.410, 95% CI: 1.404 to 29.275) was associated independently with the poor prognosis. Development of irAEs was associated with clinical benefit for HCC patients who were treated with immune checkpoint inhibitors; irAE, particularly low-grade irAE, was a predictable marker for better ICI treatment efficiency in HCC patients.


Indices to quantify changes in intracranial and cerebral perfusion pressure by assessing agreement between hourly and semi-continuous recordings.
Little published data exists on whether nurse-recorded end-hour values of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are representative of continuous monitoring during the hour. There is also no standard method of quantifying the observed perturbations in cerebral hemodynamics. This study compared the level of agreement between end-hour values and computer downloaded observations of ICP and CPP at 15-min intervals. We also developed the intracranial hypertension index and the cerebral hypoperfusion index to quantify perturbations in cerebral hemodynamics. Each of these indices relates the number of abnormal observations to the total number of observations taken. Prospective, non-interventional study. The bias and precision between the two methods for ICP and CPP were -0.002+/-2.6 mmHg and -1.1+/-6.2 mmHg, respectively. A strong correlation existed between the hourly mean calculated from the 15-min and the end-hour values for both ICP ( r(2)=0.95, p<0.0001) and CPP ( r(2)=0.78, p<0.001). The intracranial hypertension index was 40% from the 15-min measurements and 41% from the hourly observations ( p= NS). The cerebral hypoperfusion indices were 13.4% and 13.1% with the 15-min and end-hour values, respectively ( p= NS). The end-hour values of ICP and CPP are as accurate as more frequent measurements during the hour and are adequate for purposes of epidemiological research and medico-legal audit. The intracranial hypertension and cerebral hypoperfusion indices may be useful in describing cerebral hemodynamics for future interventional studies and for assessing quality in the delivery of neuro-critical care.


Sex differences in the impact of day/night distribution of ST-segment elevation myocardial infarction onset on in-hospital outcomes: findings from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project.
Circadian system plays an important role in cardiovascular health. Experimental studies have also identified sex differences in circadian system. We aim to explore the impact of sex on the association between symptom-onset pattern of STEMI and in-hospital adverse outcomes in Chinese population. Data were used from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project. 18271 STEMI patients undergoing primary percutaneous coronary intervention entered the study, including 14785 (80.9%) men and 3486 (19.1%) women. The outcomes included all-cause mortality and a composite of major adverse cardiovascular and cerebrovascular events (MACCE) during hospitalization. Most participants experienced STEMI onset during 06:00 h to noon, and there was no difference in onset pattern between men and women (p = 0.582). Logistic regression showed that, after adjustment for cardiovascular risk factors, symptom onset time was significantly associated with in-hospital mortality in men, but not in women or the total population. The odds ratios (ORs) for male patients were 1.86 (95% CI 1.05 to 3.27) for midnight to 06:00 h, 1.58 (95% CI 0.95 to 2.64) for 06:00 h to noon, and 0.80 (95% CI 0.49 to 1.73) for 18:00 h to midnight as compared with STEMI presenting during noon to 18:00 h. But symptom onset time was not associated with MACCE in both sexes or the entire cohort. These findings show that STEMI onset time was independently associated with in-hospital mortality in male Chinese patients, indicating that sex should be taken into account in studying impact of circadian system on myocardial infarction.


Effects of chronic hyperinsulinaemia on hepatic enzymes involved in lipogenesis and carbohydrate metabolism in the young rat.
Chronic (6 days) hyperinsulinaemia in young rats produced lower blood glucose concentrations and augmented body- and liver-weight gain. The insulin-treated rats had increased hepatic activities of citrate-cleavage enzyme, 'malic' enzyme and high-substrate (6.6 mM-phosphoenolpyruvate) pyruvate kinase, and decreased glucose 6-phosphatase. There were no changes in activities of phosphoenolpyruvate carboxykinase, phosphofructokinase, low-substrate (1.3 mM-phosphoenolpyruvate) pyruvate kinase, glucokinase and hexokinase.


The neural and genetic basis of executive function: attention, cognitive flexibility, and response inhibition.
Executive function is a collection of cognitive processes essential for higher order mental function. Processes involved in executive function include, but are not limited to, working memory, attention, cognitive flexibility, and impulse control. These complex behaviors are largely mediated by prefrontal cortical function but are modulated by dopaminergic, noradrenergic, serotonergic, and cholinergic input. The ability of these neurotransmitter systems to modulate executive function allows for adaptation in cognitive behavior in response to changes in the environment. Because of the important role these neurotransmitter systems play in regulating executive function, changes in these systems can also have a grave impact on executive function. In addition, polymorphisms in genes associated with these neurotransmitters are associated with phenotypic differences in executive function. Understanding how these naturally occurring polymorphisms contribute to different executive function phenotypes will advance basic knowledge of cognition and potentially further understanding and treatment of mental illness that involve changes in executive function. In this review, we will examine the influence of dopamine, norepinephrine, serotonin, and acetylcholine on the following measures of executive function: attention, cognitive flexibility, and impulse control. We will also review the effects of polymorphisms in genes associated with these neurotransmitter systems on these measures of executive function.


Effect of porin loss on the activity of tigecycline against Klebsiella pneumoniae producing extended-spectrum beta-lactamases or plasmid-mediated AmpC-type beta-lactamases.
Tigecycline showed excellent in vitro activity against 50 clinical isolates of Klebsiella pneumoniae producing extended-spectrum beta-lactamases, plasmid-mediated AmpC-type beta-lactamases, or both. This activity was not affected by porin loss. Porin loss, however, did affect the activity of imipenem against strains that expressed both types of enzymes.


Evaluation of estrogen receptor expression and its relationship with clinicopathologic findings in gastric cancer.
The presence of estrogen receptor alpha has been reported in the cell and tissue levels in gastric cancer; however, its impact on patients' survival remains unclear. The aim of this study was to investigate the expression of estrogen receptor in gastric carcinoma as well as its relationship with the clinicopathologic findings of the patients. The study was performed on 100 endoscopic biopsies of gastric adenocarcinoma for estrogen receptor expression using an immunohistochemical method, and their relationship with the clinicopathologic findings of the patients, such as age, gender, tumor site, size, grade, depth of tumor invasion (T), and lymphatic status (N), were analyzed using independent sample t-test and Pearson Chi-square test. A P < 0.05 was considered significant in all analyses. Using an immunohistochemical method on endoscopic biopsies of 74 males and 26 females with the mean age of 63 years, estrogen receptor was found to be positive in 41% of patients. No significant difference was found between estrogen receptor expression and other clinicopathologic findings (P = 0.75). There was a significant difference between estrogen receptor (+) and estrogen receptor (-) groups in nodal involvement (P = 0.001). The estrogen receptor (+) patients had more number of lymph nodes involved. This study showed that lymph node involvement has a significant relationship with estrogen receptor expression. However, no significant relationship was found between estrogen receptor expression and other clinicopathologic findings such as age, gender, tumor site in stomach, tumor size, tumor grade, and T-stage.


Progesterone receptor measurement by isoelectric focusing: a potential microassay.
Sixty-two selected breast cancers were used to compare the conventional dextran-coated charcoal (DCC) assay with a new method of separating progesterone receptor by isoelectric focusing in flat beds of agarose gel. Ninety assays were performed. Isoelectric focusing indicated correctly the presence of receptor in 92% and the absence of receptor in 86% of assays, when compared with the DCC assay. The relationship between the results of the two methods was linear. Isoelectric focusing underestimated receptor to a variable extent, finding relatively less receptor at higher absolute levels of binding than at lower levels. The lower limit of sensitivity of isoelectric focusing was 30 fmol/ml cytosol. The protein concentrations of cytosols prepared from 46 needle biopsy samples (mean weight 25 mg) ranged from 0.5 to 30 g/l (median 4 g/l, 10th percentile 0.75 g/l). Isoelectric focusing is a satisfactory method of progesterone receptor measurement and can be applied to samples too small for conventional techniques.


Vincristine (NSC-67574), cytosine arabinoside (NSC-63878), 6 thioguanine (NSC-752) and daunorubicin (NSC-82151) (VAT-D): a pilot study of combination chemotherapy for remission induction in acute myeloid leukemia in adults.
Fifteen newly diagnosed unselected adult patients with acute nonlymphocytic leukemia were treated in a pilot study of the combination of vincristine, cytosine arabinoside, 6-thioguanine, and daunorubicin (VAT-D) for remission induction therapy. Eleven of fifteen (75%) achieved a remission bone marrow. Median duration of remission was seven months in all responders (11 patients). The 11 patients achieving initial remission reached a median survival of 14 months. Twelve of seventeen attempts at reinduction of remission with VAT-D were successful. The total amount of daunorubicin required for induction was less than that required in the majority of reported acute leukemia treatment regimens utilizing daunorubicin.


Tranexamic acid administration for arthroscopic rotator cuff repair: A prospective, double-blind, randomized controlled trial.
The purpose of this study was to compare the efficacy of tranexamic acid versus placebo after arthroscopic rotator cuff repair. This prospective, double-blind, and randomized study involved 66 patients who consecutively underwent arthroscopic rotator cuff repair from 2020 to 2021 at our hospital. Thirty-three shoulders each were randomly assigned to the tranexamic acid and control groups. In the former group, 1000 mg of tranexamic acid (20 mL) was administered intravenously 10 min before surgery and the same volume of normal saline (20 mL) was administered intravenously in the control group. We evaluated visual clarity; visual analog scale pain scores at rest, during activity, and at night; the circumference and diameter of the shoulder joint in the groups before and after the surgery at 1, 2, and 3 days, and 1 week; estimated perioperative blood loss; and operative time. Visual clarity was rated using a numeric rating scale from grade 1 (poor) to grade 3 (clear) every 15 min throughout the surgery. We compared and analyzed the results between the groups. Statistical significance was set at a p-value of <0.05. Visual clarity was found to be significantly better in the tranexamic acid group, with a greater percentage of grade 3 visual clarity (75.6 ± 11.2% vs 68.1 ± 13.4%, p = 0.045). The visual analog scale scores at rest and at night in the control group were significantly lower than those in the tranexamic acid group for 1 week postoperatively (13.8 ± 14.8 vs 5 ± 9.3, p = 0.008, 36.1 ± 23.3 vs 19.3 ± 24, p = 0.012). The circumference and diameter of the shoulder joint, estimated perioperative blood loss, and operative time were not significantly different between the two groups. Intravenous administration of tranexamic acid is an alternative way to improve visual clarity in arthroscopic rotator cuff repair; however, there are no other significant differences compared to the administration of placebo.


Nexus formation in the myometrium during parturition and induced by estrogen.
The occurence of nexuses (gap junctions) in mouse uterine smooth muscle was found to depend on the hormonal state. As revealed by freeze-fracture electron microscopy, nexuses are virtually absent in virginal and pregnant mice. Abundant, large-sized nexuses were observed in the myometrium during parturition. Estrogen application to virginal mice also induced an increase in number and size of nexuses. Our observations indicate that a new formation of nexuses occurs in differentiated cells. New nexuses may be formed by the confluence of nexus subunits preexisting in the cell membrane or by newly biosynthesized components.


Measuring the construct of executive control in schizophrenia: defining and validating translational animal paradigms for discovery research.
Executive control is an aspect of cognitive function known to be impaired in schizophrenia. Previous meetings of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) group have more precisely defined executive control in terms of two constructs: "rule generation and selection", and "dynamic adjustments of control". Next, human cognitive tasks that may effectively measure performance with regard to these constructs were identified to be developed into practical and reliable measures for use in treatment development. The aim of this round of CNTRICS meetings was to define animal paradigms that have sufficient promise to warrant further investigation for their utility in measuring these constructs. Accordingly, "reversal learning" and the "attentional set-shifting task" were nominated to assess the construct of rule generation and selection, and the "stop signal task" for the construct of dynamic adjustments of control. These tasks are described in more detail here, with a particular focus on their utility for drug discovery efforts. Presently, each assay has strengths and weaknesses with regard to this point and increased emphasis on improving practical aspects of testing, understanding predictive validity, and defining biomarkers of performance represent important objectives in attaining confidence in translational validity here.


Relationship between hair cortisol concentrations and depressive symptoms in patients with coronary artery disease.
Concentrations of cortisol in hair, a novel marker of longer-term cortisol status, were compared in depressed versus nondepressed patients with coronary artery disease (CAD). 20 mg hair samples of 3 cm length were collected from 121 patients attending a cardiac rehabilitation program, 34 of whom suffered from depressive symptoms. Controlling for age, gender, coronary artery bypass grafting, history of depression, and time since most recent acute coronary syndrome, cortisol concentrations (P = 0.162) did not predict severity of depression. Younger age (P = 0.003) was a significant predictor of depressive symptoms. Perceived stress was not associated with long-term cortisol concentrations (P = 0.161). Cortisol concentrations in hair do not predict depressive symptoms in CAD patients attending cardiac rehabilitation.


A report of the number of adolescents screened as warranting further investigation for depression and social anxiety in a pre-operative cohort with idiopathic scoliosis.
Adolescent Idiopathic Scoliosis (AIS) is a common form of scoliosis, causing rotational deformity of the torso in a teenage population. In AIS this happens at a time of particular psychological development and vulnerability and a link between AIS and mental health problems has been observed. Over a 6 month period, all patients with AIS aged 10-18 referred to a single spinal deformity centre in the UK were screened for symptoms suggestive of a potential diagnosis of depression and social anxiety. Of the 33 patients surveyed, 6 (18%) had scores worthy of further assessment for a potential diagnosis of depression and 19 (59%) worthy of further assessment for a potential diagnosis of social anxiety. This small study supports the notion that there is an association between AIS and mental health issues. These initial findings support the practice of routine mental health screening in AIS.


A review of mercury exposure among artisanal small-scale gold miners in developing countries.
Extraction of gold using mercury has been a way out of poverty for millions of people in developing countries. Artisanal small-scale gold mining (ASGM) has expanded during the last decades and is often carried out under primitive conditions. Thus, workers in this industry may be exposed to high levels of mercury and suffer from toxic effects from mercury exposure. The objective of this review was to provide an outline of the studies available on elemental mercury exposure among artisanal small-scale gold miners. Searching the PubMed and Embase databases, 26 studies with a total of 3,005 exposed subjects and 442 controls across 14 different developing countries were found. Urine mercury levels were used as biomarkers of exposure. In general, the urine mercury levels were elevated and a considerable proportion of workers had urine mercury levels above existing guidelines. Exposed subjects were stratified into residents, miners, millers, smelters, and refiners, who by work task content were expected to be increasingly exposed to mercury. This group order did show a clear trend of increasing mercury levels. Mercury levels differed substantially between studies. Possible explanations include dissimilarities in gold extraction methods, use of protective devices, and selection of participants. This review provides evidence that artisanal gold miners and residents of the mining sites are exposed to mercury vapour to an extent where acute and long-term toxic effects of mercury are likely. Interventions aimed at reducing exposure and emission of mercury from ASGM are needed.


Relationship between antifungal activity and hydrophobicity of kojic acid derivatives.
Twenty three kojic acid derivatives were tested in the agar diffusion test against twenty five dermatophytic fungi. The inhibitory effects at equal doses (10 mg/L) were correlated with the 1-octanol-water partition coefficients of the compounds. An improvement in antifungal activity can be achieved by increasing the hydrophobicity of the compounds.


Carotid artery: percutaneous transbrachial selective arteriography with a 4-F catheter.
Bilateral selective common carotid artery catheterization was attempted in 72 patients by means of percutaneous placement of a 4-F catheter from a right brachial artery puncture site in the antecubital fossa. The success rate was high (95.8%) and the complication rate low (6.9%), and there were no instances of brachial artery spasm or thrombosis. The experience, while small, suggests that selective common carotid arteriography can be done safely and efficaciously from the right brachial artery approach.


Assessment of Scientific Reasoning: the Effects of Task Context, Data, and Design on Student Reasoning in Control of Variables.
Scientific reasoning is an important component under the cognitive strand of the 21st century skills and is highly emphasized in the new science education standards. This study focuses on the assessment of student reasoning in control of variables (COV), which is a core sub-skill of scientific reasoning. The main research question is to investigate the extent to which the existence of experimental data in questions impacts student reasoning and performance. This study also explores the effects of task contexts on student reasoning as well as students' abilities to distinguish between testability and causal influences of variables in COV experiments. Data were collected with students from both USA and China. Students received randomly one of two test versions, one with experimental data and one without. The results show that students from both populations (1) perform better when experimental data are not provided, (2) perform better in physics contexts than in real-life contexts, and (3) students have a tendency to equate non-influential variables to non-testable variables. In addition, based on the analysis of both quantitative and qualitative data, a possible progression of developmental levels of student reasoning in control of variables is proposed, which can be used to inform future development of assessment and instruction.


A review of DDT resistance as it pertains to the 91-C and 91-R strains in Drosophila melanogaster.
While insecticide resistance presents a challenge for those intent on controlling insect populations, these challenges have also generated a set of tools that can be used to ask fundamental biological questions about that resistance. Numerous species of insects have evolved resistance to multiple classes of insecticides. Each one of these species and their respective resistant populations represent a potential tool for understanding the molecular basis of the evolution of resistance. However, in-laboratory maintenance of resistant insect populations (and their comparative susceptible populations) suitable for asking the needed set of questions around the molecular consequences of long-term pesticide exposure requires a significant, in places prohibitive, level of resources. Drosophila melanogaster (hereafter referred to as Drosophila) is a model insect system with populations easily selected with pesticides and readily maintainable over decades. Even within Drosophila, however, few populations exist where long-term pesticide selection has occurred along with contrasting non-selected population. As such, the Drosophila 91-C and 91-R populations, which exhibit insecticide resistance to DDT (91-R), compared to a non-selection population (91-C), represent a unique resource for the study of high level DDT resistance. Moreover, with the availability of "omics" technologies over the past several decades, this paired population has emerged as a useful tool for understanding both the molecular basis of pesticide resistance and the molecular consequences of long-term pesticide exposure. In this review, we summarize the studies with these aforementioned populations over the past several decades, addressing what has been learned from these efforts.


The Methylated DNA Immunoprecipitation [MeDIP] to Investigate the Epigenetic Remodeling in Cell Fate Determination and Cancer Development.
Epigenetic mechanisms such as DNA methylation, posttranslational modifications of histone proteins, remodeling of nucleosomes, and the expression of noncoding RNAs contribute to the regulation of gene expression for the cell fate determination and tissue development. The disruption of these epigenetic mechanisms, in conjunction with genetic alterations, is a decisive element for cancer development and progression. The cancer phenotype is characterized by global DNA hypomethylation and gene-specific hypermethylation. The methylated DNA immunoprecipitation [MeDIP] is a useful approach currently used to clarify the functional consequences of DNA methylation on cell fate determination and cancer development.


Method and Application of Reservoir Unit Division in Continental Faulted Lacustrine Basin: An Example from the L70 Fault Block in Raoyang Sag.
The continental faulted lacustrine basin is an important type of continental oil and gas basin with typical compound oil and gas accumulation characteristics. The traditional petroleum geological theory usually makes a general analysis of multiple reservoirs. It uses the structural model to understand the reservoir and has a vague understanding of the reservoir. The actual exploration is inconsistent with the traditional theory, which restricts exploration and development. In this case, taking the lower submember of Sha 1 of Shahejie Formation of L70 fault block in Raoyang sag as an example, the concept of reservoir unit is put forward, and the reservoir is redivided using the "four diagrams and four steps" method, the oil-water distribution is clarified, the type of reservoir unit is defined, and multiple potential reservoir units are proposed. It enriches and perfects the traditional petroleum geological theory, provides a new research method and idea for petroleum exploration and development, and ushers in new opportunities for the developed old oil fields.


General, robust, and stereocomplementary preparation of beta-ketoester enol tosylates as cross-coupling partners utilizing TsCl-N-methylimidazole agents.
We have developed a general, robust, and cost-effective method for the (E)- or (Z)-stereocomplementary enol tosylation of beta-ketoesters using TsCl- N-methylimidazole (NMI)-Et3N or LiOH. TsCl coupled with NMI formed a highly reactive N-sulfonylammonium intermediate. Stereocongested secondary alcohols were smoothly sulfonylated using Ts(Ms)Cl-NMI-Et3N. beta-Ketoesters underwent (E)-selective tosylation using TsCl-NMI-Et3N and (Z)-selective tosylation using TsCl-NMI-LiOH (total of 23 examples; 60%-99% yield). Stereoretentive Negishi and Sonogashira couplings using enol tosylates proceeded successfully to give trisubstituted alpha,beta-unsaturated esters.


Carer-reported measures for a dementia registry: A systematic scoping review and a qualitative study.
Informal carers play a critical role in supporting people with dementia. We conducted a scoping review and a qualitative study to inform the identification and development of carer-reported measures for a dementia clinical quality registry. Phase 1-Scoping review: Searches to identify carer-reported health and well-being measures were conducted in three databases (MEDLINE, PsycINFO and Embase). Data were extracted to record how the measures were administered, the domains of quality-of-life addressed and whether they had been used in a registry context. Phase 2-Qualitative study: Four focus groups were conducted with carers to examine the acceptability of selected measures and to identify outcomes that were important but missing from these measures. Phase 1: Ninety-nine carer measures were identified with the top four being the Zarit Burden Interview (n = 39), the Short-Form12/36 (n = 14), the Brief Coping Orientation to Problems Experienced scale and the Sense of Coherence scale (both n = 9). Modes of administration included face-to-face (n = 50), postal (n = 11), telephone (n = 8) and online (n = 5). No measure had been used in a registry context. Phase 2: Carers preferred brief measures that included both outcome and experience questions, reflected changes in carers' circumstances and included open-ended questions. Carer-reported measures for a dementia clinical quality registry need to include both outcome and experience questions to capture carers' perceptions of the process and outcomes of care and services. Existing carer-reported measures have not been used in a dementia registry context and adaption and further research are required.


Aqueous-based spinning of fibers from self-assembling structural proteins.
There has been long-standing interest in generating fibers from structural proteins and a great deal of work has been done in attempting to mimic dragline spider silk. Dragline silk balances stiffness, strength, extensibility, and high energy to break. Mimicking these properties through aqueous-based spinning of recombinant silk protein is a significant challenge; however, an approach has been developed that facilitates the formation of fibers approaching the mechanical properties seen with natural dragline silk. Due to the multitude of solution, spinning and post-spinning variables one has to consider, the method entails a multivariate approach to protein solution processing and fiber spinning. Optimization to maximize mechanical integrity of the fibers is performed by correlating the solution and spinning variables to mechanical properties and using this information for subsequent fiber spinning studies. Here, the method is described in detail and emphasizes the lessons learned during the iterative variable analysis process, which can be used as a basis for aqueous-based fiber spinning of other structural proteins.


End of Life: What Is the Anesthesiologist's Role?
Anesthesiologists receive extensive training in the area of perioperative care and the specialized skills required to maintain life during surgery and complex procedures. Integrated into almost every facet of contemporary medicine, they interact with patients at multiple stages of their health care journeys. While traditionally thought of as the doctors best equipped to save lives, they may also be some of the best doctors to help navigate the chapters at the end of life. Successfully navigating end-of-life care, particularly in the COVID-19 era, is a complicated task. Competing ethical principles of autonomy and nonmaleficence may often be encountered as sophisticated medical technologies offer the promise of extending life longer than ever before seen. From encouraging patients to actively engage in advance care planning, normalizing the conversations around the end of life, employing our skills to relieve pain and suffering associated with dying, and using our empathy and communication skills to also care for the families of dying patients, there are many ways for the anesthesiologist to elevate the care provided at the end of life. The aim of this article is to review the existing literature on the role of the anesthesiologist in end-of-life care, as well as to encourage future development of our specialty in this area.


Solvated helical backbones: x-ray diffraction study of Boc-Ala-Leu-Aib-Ala-Leu-Aib-OMe.H2O.
A second example of insertion of a water molecule into the helical backbone of an apolar peptide is presented here and compared to a similar occurrence in a longer peptide with the same type of sequence of residues, i.e., Boc-Aib-(Ala-Leu-Aib)3-OMe. The backbone of the title compound assumes an approximate 3(10)-helical form with three 4----1 hydrogen bonds. In the place of a fourth 4----1 hydrogen bond, a water molecule is inserted between O(1) and N(4), and acts as a bridge by forming hydrogen bonds N(4) ... W(1) (2.95 A) and W(1) ... O(1) (2.81 A). The water molecule participates in a third hydrogen bond with a neighboring peptide molecule, W(1) ... O(4) (2.91 A). The insertion of the water molecule causes the apolar peptide to mimic an amphiphilic helix. Crystals grown from ethyl acetate/petroleum ether (reported here) or from methanol/water solution are in space group P2(1)2(1)2(1) with a = 12.024(4) A, b = 15.714(6) A, c = 21.411(7) A, Z = 4 and dcalc = 1.124 g/cm3 for C32H58N6O9.H2O. The overall agreement factor R is 6.3% for 2707 reflections observed with intensities greater than 3 sigma(F) and the resolution is 0.90 A.


Synergistic interaction between baclofen administration into the median raphe nucleus and inconsequential visual stimuli on investigatory behavior of rats.
Noncontingent administration of amphetamine into the ventral striatum or systemic nicotine increases responses rewarded by inconsequential visual stimuli. When these drugs are contingently administered, rats learn to self-administer them. We recently found that rats self-administer the GABA(B) receptor agonist baclofen into the median (MR) or dorsal (DR) raphe nuclei. We examined whether noncontingent administration of baclofen into the MR or DR increases rats' investigatory behavior rewarded by a flash of light. Contingent presentations of a flash of light slightly increased lever presses. Whereas noncontingent administration of baclofen into the MR or DR did not reliably increase lever presses in the absence of visual stimulus reward, the same manipulation markedly increased lever presses rewarded by the visual stimulus. Heightened locomotor activity induced by intraperitoneal injections of amphetamine (3 mg/kg) failed to concur with increased lever pressing for the visual stimulus. These results indicate that the observed enhancement of visual stimulus seeking is distinct from an enhancement of general locomotor activity. Visual stimulus seeking decreased when baclofen was co-administered with the GABA(B) receptor antagonist, SCH 50911, confirming the involvement of local GABA(B) receptors. Seeking for visual stimulus also abated when baclofen administration was preceded by intraperitoneal injections of the dopamine antagonist, SCH 23390 (0.025 mg/kg), suggesting enhanced visual stimulus seeking depends on intact dopamine signals. Baclofen administration into the MR or DR increased investigatory behavior induced by visual stimuli. Stimulation of GABA(B) receptors in the MR and DR appears to disinhibit the motivational process involving stimulus-approach responses.


The perfect microsite: How to maximize Posidonia oceanica seedling settlement success for restoration purposes using ecological knowledge.
The use of sexual propagules to restore seagrass meadows has raised increasing attention in the last years as seed-based strategies avoid impacts on donor beds while preserving genetic diversity in restored populations. However, the availability of suitable microsites for seedling establishment at transplantation locations is crucial in order to achieve positive outcome of restoration actions. In this study we develop ad-hoc holders that act as optimal microsites for Posidonia oceanica seedling establishment. Holders are intended to be transferred in the field for restoration purposes after few months of indoor seedling culture. Seedling ability to self-anchor to rocky substrates via adhesive root hairs was exploited. We tested rocky holders with different designs in order to maximize seedling survival and settlement. The effect of the holder design on seedling anchorage performances was evaluated. Holders were provided with different topographical complexity and substrate slope. Topographical complexity significantly influenced settlement success, as seedlings did not attach to flat holders, while anchorage reached 100% on holders provided with complexity at seed and the root scales. Substrate slope did not affect the percentage of anchored seedlings, conversely it influenced root growth pattern and thus anchorage stability. This study shows how ecological knowledge of species' life history strategies and associated critical traits provides valuable hints to develop alternative approaches to seagrass restoration tailored to the biology of the system under study.


Explanations for attractiveness-related positive biases in an evolutionary perspective of life history theory.
The mating-related evolutionary explanation that Maestripieri et al. offer does not apply to (1) infants' positive biases toward attractive individuals and (2) adults' positive biases toward attractive infants and children. They are best understood when integrated into an evolutionary life history framework. I argue that the life history of positive biases toward attractive individuals is driven by fundamental trade-offs made throughout development.


Fatal salmonellosis in systemic lupus erythematosus.
We report the case of a 74-year-old woman with long-standing systemic lupus erythematosus (SLE) who developed Salmonella septicaemia and an aortic mycotic aneurysm which proved fatal. She had received only low dose prednisolone (average 5-10 mg) as treatment for her disease, which appeared to be inactive at the time of her presentation with septicaemia. This is the first case report of this particular manifestation of salmonellosis in SLE and the patient died despite standard antibiotic treatment. This case emphasizes the need for continued vigilance for signs of Salmonella infection when managing patients with SLE.


[Success factors and obstacles in the implementation of the "Lübeck Worlds of Movement Model" in inpatient care facilities-results of a scientific evaluation].
The Prevention Act has greatly promoted the implementation of interventions focusing on the physical activity of nursing home residents. However the goal-compliant implementation and long-term sustainability of such offers is often associated with major challenges.Over a period of 2.5 years, the program "Lübeck Worlds of Movement Model" was evaluated during its implementation in nursing homes in the city of Lübeck. The main objective was to discover promoting or inhibiting factors of the implementation process. Alongside other data collection, 52 partially structured, problem-oriented interviews were conducted with participating professionals (e.g., employees of the nursing homes, trainers). They were analyzed and structured in a topic-based manner.A number of promoting and inhibiting factors were identified. The structure of the program supports the participants' and trainers' motivation to stick to the program. However, it was not well received nor permanently adopted in all areas of the nursing homes. The lack of involvement of nursing staff and of anchoring the program in the organizational structure and culture of the facilities were two of the most important inhibiting factors. Furthermore the model is suitable only for a limited number of residents. Further adaptations and developments have to be tackled to meet the target group's needs and achieve the successful implementation and long-term sustainability of the program.


Preclinical safety evaluation of monoclonal antibodies.
Monoclonal antibodies (mAbs) can be potent and specific therapeutics with long plasma half-lives and therefore long exposure times, which are now being clinically used to treat chronic disorders. Their recombinant design means some of their behaviours in the clinic can be determined at the design stage. However, their specific nature means a flexible approach often is required for preclinical studies and the use of novel approaches including parallel reagents and specific transgenic mice are being used. The key aspects at this level to consider are the effects on safety pharmacology and long-term immune status in the preclinical species used in order to predict to people the likely result of chronic clinical usage.


Leiomyomas in both uterine remnants in a woman with the Mayer-Rokitansky-Küster-Hauser syndrome.
To describe a case of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome associated with bilateral myomas in uterine remnants. Case report. University hospital. A 35-year-old woman with MRKH syndrome and pelvic pain, in whom leiomyomas were diagnosed by imaging techniques. Diagnostic laparoscopy followed by excision of leiomyomas and uterine remnants by laparotomy. Resolution of symptoms and histologic confirmation of the clinic diagnosis. After a 6-month follow-up period, the patient was asymptomatic. The histologic examination confirmed MRKH syndrome associated with multiple myomas in both rudimentary uteri. This is an unusual case of MRKH syndrome associated with bilateral leiomyomas. The excision of the tumors with the adjacent uterine remnants is indicated when they are symptomatic.


Corynebacterium-induced cystitis with mucosal incrustations.
Alkaline-incrusted cystitis is a rare condition that was first described more than 70 years ago. Since then few cases have been reported. To our knowledge, we report the second such case in the literature in which Corynebacterium D2 was considered as the causative factor of incrusted cystitis.


Synthesis of Pharmacological Relevant 1,2,3-Triazole and Its Analogues-A Review.
In this review, authors focus mostly on the various synthetic strategies developed so far for 1,2,3- triazole scaffold and its derivatives via different approaches such as metal-free, metal assisted or bimetallic. A brief overview of applications of the very important 1,2,3-triazole scaffold along with pharmacological activity is also discussed. Synthetic strategies are updated until June 2020.


Does exogenous nitric oxide influence tympanosclerosis? An experimental study.
We aimed to elucidate the effects of exogenous nitric oxide application via myrigotomized rat tympanic membranes on tympanosclerosis. Forty male rats were included in the study. After myringotomy, nitric oxide was given to the left tympanic cavities and saline was given to the right as the control group. The procedure was repeated 3 times with weekly intervals. Three months after the first procedure, otomicroscopic examination was made and the rats were sacrificed for histologic examination. Neither otomicroscopic examination, nor histologic examination of middle ears and tympanic membranes revealed any significant difference between the right and left sides. Tympanic membrane thicknesses were also similar on both sides without showing any significant difference. Data from this study indicate that exogenous nitric oxide application did not change the occurence of tympanosclerosis in the rat model. Other cytokine interactions are needed to start the reaction sequence leading to tympanosclerosis.


[Mechanical thrombectomy: Acute complications and delayed sequelae].
Due to the positive evidence for mechanical thrombectomy (mTE), it will be increasingly used in future. Profound knowledge of potential complications, prevention and management of complications is necessary to safely implement mTE into clinical practice. Description of specific complications of mTE and their clinical relevance, measures for prevention and management. Summary of the current knowledge on long-term side effects of mTE. Analysis of current trial results and selected case series to address specific topics. Summary of own practical clinical experience. Vascular injury (1-5%) and emboli (5-9%) are the most relevant intraprocedural complications but the clinical outcome is variable. Measures for prevention and management are described in detail. Vasospasms frequently occur (20-26%) but rarely need specific treatment and do not affect the clinical course. In the case of restrictive indications the frequency of symptomatic hemorrhage is similar to that for medicinal treatment (up to 8%). Contrast medium enhancement in the area of the infarction on post-treatment imaging should not be mistaken for hemorrhages. Focal subarachnoid contrast medium enhancement or hemorrhage occurs in up to 24% of cases and is predominantly benign. In follow-up imaging stenoses or occlusions can be detected in 4-10% of the treated vessels, most of which are asymptomatic. They are considered to be caused by microtrauma to the vascular wall. Clinically relevant complications of mTE are rare. Preventive measures and effective management of complications may even increase safety. Stenoses occasionally occur as a long-term side effect but are asymptomatic in the majority of cases.


Microplastic accumulation via trophic transfer: Can a predatory crab counter the adverse effects of microplastics by body defence?
Microplastics are considered detrimental to aquatic organisms due to their potential accumulation along food chains. Thus, it is puzzling why some of them appear unaffected by microplastics. Here, we assessed the contribution of water filtration and food consumption to microplastic accumulation in a predatory marine crab (Charybdis japonica) and examined the associated impacts of microplastics (particle size: 5 μm) following ingestion for one week. Results showed that water filtration and food consumption contributed similarly to the accumulation of microplastics, which were distributed among organs in this order: hepatopancreas > guts > gills > muscles. Yet, biomagnification (i.e. accumulation through consumption of microplastic-contaminated mussels) did not occur possibly due to egestion of microplastics. The crabs upregulated detoxification capacity (EROD) and antioxidant defence (GST) in response to the microplastics accumulated in their tissues. However, these defence mechanisms collapsed when the microplastic concentration in hepatopancreas exceeded ~3 mg g-1, leading to severe hepatic injury (elevated AST and ALT) and impaired neural activity (reduced AChE). Our results suggest that marine organisms have an innate capacity to counter the acute effects of microplastics, but there is a limit beyond which the defence mechanisms fail and hence physiological functions are impaired. As microplastic pollution will deteriorate in the future, the fitness and survival of marine organisms may be undermined by microplastics, affecting the stability and functioning of marine ecosystems.


Translation, Adaptation, and Validation of the Malay Version of the Barriers to Access to Care Questionnaire for Assessing the Barriers to Seeking Mental Health Care Among the Health Workforce in the East Coast Region of Peninsular Malaysia.
Background Mental health problems among the health workforce are a significant concern worldwide, including in Malaysia. Unfortunately, some health workforce may perceive various barriers or challenges that prevent them from seeking help. Identifying and addressing these barriers is crucial for enhancing mental health services and support. The Barriers to Access to Care Evaluation (BACE-3) questionnaire is a valuable tool that can be used for assessing these barriers among health workers. However, a validated Malay version is needed. Therefore, this study aims to translate, adapt, and validate the original version of Barriers to Access to Care Evaluation (BACE-3) into the Malay version (MBACE). Methods A rigorous process of translation and adaptation was followed to develop the Malay version of the BACE-3 questionnaire (MBACE). A cross-sectional study was conducted to assess the psychometric properties of the questionnaire, with purposive sampling employed to recruit 188 participants from various job categories, including doctors, nurses, pharmacists, and non-clinical staff, such as health assistants and clerks. The analysis was conducted using the R software version 4.2.2 (R Foundation, Vienna, Austria). Construct validity was determined using confirmatory factor analysis (CFA). To assess the convergent validity, internal consistency, and reliability of the instrument, measures such as the average variance extracted (AVE), composite reliability (CR), and Cronbach's alpha values were calculated. Results During the CFA process, two items with a factor loading less than 0.5 (items 15 and 16) were removed to improve the convergent validity and model fit. The CFA results revealed that the 2-factor model MBACE had good construct validity (root mean square error of approximation (RMSEA) = 0.053; comparative fit index (CFI) = 0.939; Tucker-Lewis fit index (TLI) = 0.934). The internal consistency was supported by Cronbach's alpha values ranging from 0.92 to 0.94 for the stigma factor and non-stigma factor. The average variance extracted (AVE) and composite reliability (CR) values further supported the questionnaire's reliability and convergent validity. Conclusion The translated and adapted 28-item MBACE questionnaire is a valid and reliable tool for assessing the barrier to seeking professional mental health care among the Malaysian health workforce. This instrument has the potential to aid in the development of targeted interventions to promote mental health help-seeking behavior and enhance the well-being of the Malaysian health workforce.


Reduction of cholecystokinin-8S-neurons in the paraventricular hypothalamic nucleus of neonatally overfed weanling rats.
Cholecystokinin (CCK) is suggested to be involved, e.g. in the central nervous modulation of food intake, possibly by acting within specific hypothalamic nuclei. Perinatal overnutrition predisposes to permanent obesity and hyperphagia, while underlying mechanisms are unclear. By reducing the litter size from the 3rd to 21st day of life, early overnutrition was induced in newborn rats. At weaning, clear overweight (P < 0.001), hyperglycaemia (P < 0.05), hyperinsulinaemia (P < 0.001), and insulin resistance (P < 0.001) occured. These early signs of obesity were associated with a significantly decreased number of CCK-positive neurons in the paraventricular hypothalamic nucleus (P < 0.002). In conclusion, due to neonatal overfeeding malformation of CCKergic neurons at the end of the critical hypothalamic differentiation period occurs. Long-term consequences on CCK-related neuroendocrine regulations could be suggested, including those affecting food intake and body weight gain.


Preliminary crystallographic data on a ferredoxin from Desulfovibrio desulfuricans (Norway strain).
The ferredoxin (Fd I) (Mr2 X 6000, one (4 Fe-4 S) cluster per subunit) from the sulphate-reducing bacteria Desulfovibrio desulfuricans Norway 4 has been crystallized. The space group is P4(2)32 with a = 71.8 A. The two monomers of the molecule are probably related by a dyad axis.


Characterization and preliminary anticonvulsant assessment of some 1,3,4-thiadiazole derivatives.
The aim of this study was to perform the anticonvulsant screening test to select some 1,3,4-thiadiazole derivatives that could offer a distinct protection against maximal electroshock (MES)-induced seizures in mice. The screening test was performed for 13 tested compounds administered intraperitoneally (ip) in a constant dose of 300 mg/kg at various pretreatment times (i.e., 15, 30, 60 and 120 min) before the MES test. Additionally, the active compounds in the screening test were subsequently subjected to the MES test that allowed determination of their median effective doses (ED50 values). Only 2 out of 13 tested 1,3,4-thiadiazole derivatives i.e., 5-butyl-; and 5-heptyl-substituted in the heterocyclic ring 1,3,4-thiadiazoles produced a distinct protection against MES-induced tonic seizures in mice. Time-course and dose-response effects revealed that 5-butyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole produced its maximum anticonvulsant action at 15 min after its ip administration to mice. In contrast, 5-heptyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole exerted the maximum anticonvulsant action at 60 min after its ip administration to mice. The ED50 values for 5-butyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole ranged between 247 and >500 mg/kg, whereas those for 5-heptyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole ranged between 233 and >500 mg/kg. 5-Butyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole and 5-heptyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole could become potentially favorable antiepileptic drugs, if the results from this study were to be extrapolated into clinical settings.


Integrating the Left Atrium Diameter to Improve the Predictive Ability of the Age, Creatinine, and Ejection Fraction Score for Atrial Fibrillation Recurrence After Cryoballoon Ablation.
Several clinical trials have assessed predictors for atrial fibrillation recurrence following cryoballoon catheter ablation. With these predictors, a practical and new scoring system can be developed to evaluate atrial fibrillation recurrence. The present study aimed to analyze the predictive value of the age, creatinine, and ejection fraction-left atrium score for potential recurrence of atrial fibrillation following cryoballoon catheter ablation in patients with symptomatic paroxysmal or persistent atrial fibrillation. We retrospectively analyzed records of patients undergoing cryoballoon cath-eter ablation. atrial fibrillation recurrence was defined as an emerging atrial fibrillation episode around 12-month follow-up (with the exclusion of a 3-month blanking period). Univariate and multivariate analyses were performed to assess predictors of atrial fibrillation recurrence. In addition, receiver operating characteristic analysis was harnessed to evaluate the performance of the age, creatinine, and ejection fraction, left atrium score in determining the risk of atrial fibrillation recurrence. The study population comprised 106 subjects (age 52 ± 13 years, 63.2% women) with paroxysmal (84.9%, n = 90) or persistent (15.1%, n = 16) atrial fibrillation. age, creatinine, and ejection fraction, left atrium score was significantly higher in subjects with atrial fibrillation recurrence in comparison to those with the maintenance of sinus rhythm. However, on multivariate logistic regression analysis, only the age, creatinine, and ejection fraction, left atrium score (OR = 12.93, 95% CI: 2.22-75.21, P =.004) served as an independent predictor of atrial fibrillation recurrence following cryoballoon catheter ablation. Age, creatinine, and ejection fraction, left atrium score had an independent association with the risk of atrial fibrillation recurrence in subjects with atrial fibrillation undergoing cryoballoon catheter ablation. Therefore, this score might potentially serve as a useful tool for risk stratification of patients with atrial fibrillation.


Is the expansion of the subway network alone capable of improving local air quality? A study case in São Paulo, Brazil.
One of the policies adopted to reduce vehicular emissions is subway network expansion. This work fitted interrupted regression models to investigate the effects of the inauguration of subway stations on the mean, trend, and seasonality of the NO, NO2, NOx, and PM10 local concentrations. The regions investigated in the city of São Paulo (Brazil) were Pinheiros, Butantã, and St. Amaro. In Pinheiros, after the inauguration of the subway station, there were downward trends for all pollutants. However, these trends were not significantly different from the trends observed before. In Butantã, only regarding NO, there was a significant reduction and seasonal change after the subway station's inauguration. In St. Amaro, no trend in the PM10 concentration was noted. The absence of other transportation and land use policies in an integrative way to the subway network expansion may be responsible for the low air quality improvement. This study highlights that the expansion of the subway network must be integrated with other policies to improve local air quality.


ViLoN-a multi-layer network approach to data integration demonstrated for patient stratification.
With more and more data being collected, modern network representations exploit the complementary nature of different data sources as well as similarities across patients. We here introduce the Variation of information fused Layers of Networks algorithm (ViLoN), a novel network-based approach for the integration of multiple molecular profiles. As a key innovation, it directly incorporates prior functional knowledge (KEGG, GO). In the constructed network of patients, patients are represented by networks of pathways, comprising genes that are linked by common functions and joint regulation in the disease. Patient stratification remains a key challenge both in the clinic and for research on disease mechanisms and treatments. We thus validated ViLoN for patient stratification on multiple data type combinations (gene expression, methylation, copy number), showing substantial improvements and consistently competitive performance for all. Notably, the incorporation of prior functional knowledge was critical for good results in the smaller cohorts (rectum adenocarcinoma: 90, esophageal carcinoma: 180), where alternative methods failed.


Equine and canine Anaplasma phagocytophilum strains isolated on the island of Sardinia (Italy) are phylogenetically related to pathogenic strains from the United States.
The presence of Anaplasma phagocytophilum, a tick-transmitted zoonotic pathogen, was investigated in Sardinia using a molecular approach. Phylogenetic analysis revealed that Sardinian strains are genetically distinct from the two lineages previously described in Europe and are closely related to strains isolated in different areas of the United States.


Physiology of Sporolactobacillus strains isolated from different habitats and the indication of in vitro antagonism against Bacillus species.
In an ecological study only low numbers of Sporolactobacillus were found in habitats such as the faeces of herbivores, the rumen of cattle and the final waste water of an abattoir. Their presence in the final waste water of an abattoir indicates their possible association with food, and, more specifically, with meat. Differences were found in some physiological characteristics. One isolate (L2404) differed from the authentic Sporolactobacillus ATCC 15538 by its inability to ferment inulin, its growth in presence of 6.5% NaCl and in 0.2% tellurite, by the isomer(s) of lactic acid produced and the mol% G + G in the DNA. One Sporolactobacillus isolate (L2407) showed antagonism against Bacillus cereus, Bacillus cereus var, mycoides, Bacillus megaterium and Bacillus subtilis.


Analysis of Autophagic Vesicles in Mitotic Cells.
The detection of autophagic vesicles in interphase cells is well characterized with markers such as LC3, SQSTM1 (also known as p62) and LAMP2, which are commonly used in immunofluorescence and biochemistry assays to evaluate the status of autophagy in adherent cells. During mitosis, cells undergo important morphological changes which alter the position of the central plane, therefore the imaging of dividing cells has to be specifically designed. Here, we describe a method to label and image autophagic vesicles in mitotic cells to systematically analyze their number, morphology and distribution.


A radiofrequency coil to facilitate task-based fMRI of awake marmosets.
The small common marmoset (Callithrix jacchus) is an ideal nonhuman primate for awake fMRI in ultra-high field small animal MRI scanners. However, it can often be challenging in task-based fMRI experiments to provide a robust stimulus within the MRI environment while using hardware (an RF coil and restraint system) that is compatible with awake imaging. Here we present an RF coil and restraint system that permits unimpeded access to an awake marmoset's head subsequent to immobilization, thereby permitting the setup of peripheral devices and stimuli proximal to the head. As an example application, an fMRI experiment probing whole-brain activation in response to marmoset vocalizations was conducted-this paradigm showed significant bilateral activation in the inferior colliculus, medial lateral geniculate nucleus, and auditory cortex. The coil performance was evaluated and compared to a previously published restraint system with integrated RF coil. The image and temporal SNR were improved by up to 58 % and 27 %, respectively, in the peripheral cortex and by 30 % and 3 % in the centre of the brain. The restraint-system topology limited head motion to less than 100 µm of translation and 0.30° of rotation when measured over a 15-minute acquisition. The proposed hardware solution provides a versatile approach to awake-marmoset imaging and, as demonstrated, can facilitate task-based fMRI.


Neurocysticercosis in free roaming pigs--a slaughterhouse survey.
To investigate the prevalence of neurocysticercosis among free ranging pigs and to study the type of pathomorphological lesions in affected brains, a total of 200 brains were collected from pigs slaughtered at a local abattoir, between August, 2005 to March, 2006. Gross and histopathological examination revealed 3% (6/200) occurrence of neurocysticercosis in pigs. Taenia solium cysticercosis is an under-rated zoonosis and is a leading cause of epilepsy due to neurocysticercosis in human population of India. The prevailing situation warrants immediate implementation of effective control measures for this dreaded disease.


Tissue-Specific Distribution of iNKT Cells Impacts Their Cytokine Response.
Three subsets of invariant natural killer T (iNKT) cells have been identified, NKT1, NKT2, and NKT17, which produce distinct cytokines when stimulated, but little is known about their localization. Here, we have defined the anatomic localization and systemic distribution of these subsets and measured their cytokine production. Thymic NKT2 cells that produced interleukin-4 (IL-4) at steady state were located in the medulla and conditioned medullary thymocytes. NKT2 cells were abundant in the mesenteric lymph node (LN) of BALB/c mice and produced IL-4 in the T cell zone that conditioned other lymphocytes. Intravenous injection of α-galactosylceramide activated NKT1 cells with vascular access, but not LN or thymic NKT cells, resulting in systemic interferon-γ and IL-4 production, while oral α-galactosylceramide activated NKT2 cells in the mesenteric LN, resulting in local IL-4 release. These findings indicate that the localization of iNKT cells governs their cytokine response both at steady state and upon activation.


Bone marrow cells expressing clara cell secretory protein increase epithelial repair after ablation of pulmonary clara cells.
We have previously reported a subpopulation of bone marrow cells (BMC) that express Clara cell secretory protein (CCSP), generally felt to be specific to lung Clara cells. Ablation of lung Clara cells has been reported using a transgenic mouse that expresses thymidine kinase under control of the CCSP promoter. Treatment with ganciclovir results in permanent elimination of CCSP(+) cells, failure of airway regeneration, and death. To determine if transtracheal delivery of wild-type bone marrow CCSP(+) cells is beneficial after ablation of lung CCSP(+) cells, transgenic mice were treated with ganciclovir followed by transtracheal administration of CCSP(+) or CCSP(-) BMC. Compared with mice administered CCSP(-) cells, mice treated with CCSP(+) cells had more donor cells lining the airway epithelium, where they expressed epithelial markers including CCSP. Although donor CCSP(+) cells did not substantially repopulate the airway, their administration resulted in increased host ciliated cells, better preservation of airway epithelium, reduction of inflammatory cells, and an increase in animal survival time. Administration of CCSP(+) BMC is beneficial after permanent ablation of lung Clara cells by increasing bronchial epithelial repair. Therefore, CCSP(+) BMC could be important for treatment of lung diseases where airways re-epithelialization is compromised.


Tyrosine phosphorylation and bacterial virulence.
Protein phosphorylation on tyrosine has emerged as a key device in the control of numerous cellular functions in bacteria. In this article, we review the structure and function of bacterial tyrosine kinases and phosphatases. Phosphorylation is catalyzed by autophosphorylating adenosine triphosphate-dependent enzymes (bacterial tyrosine (BY) kinases) that are characterized by the presence of Walker motifs. The reverse reaction is catalyzed by three classes of enzymes: the eukaryotic-like phosphatases (PTPs) and dual-specific phosphatases; the low molecular weight protein-tyrosine phosphatases (LMW-PTPs); and the polymerase-histidinol phosphatases (PHP). Many BY kinases and tyrosine phosphatases can utilize host cell proteins as substrates, thereby contributing to bacterial pathogenicity. Bacterial tyrosine phosphorylation/dephosphorylation is also involved in biofilm formation and community development. The Porphyromonas gingivalis tyrosine phosphatase Ltp1 is involved in a restraint pathway that regulates heterotypic community development with Streptococcus gordonii. Ltp1 is upregulated by contact with S. gordonii and Ltp1 activity controls adhesin expression and levels of the interspecies signal AI-2.


A mobile health intervention to encourage physical activity in children: a randomised controlled trial.
Despite immense benefits of physical activity on health and developmental outcomes, few children achieve recommended daily levels of physical activity. Given more than half of families with children own a dog, we investigated the effect of a mobile health (mHealth) intervention to encourage dog-facilitated physical activity through increased family dog walking and children's active play with their dog. The PLAYCE PAWS study was a three-armed randomised pilot trial conducted in Perth, Western Australia. Children aged 5-10 years with a family dog were randomised to 4 weeks of either 1) SMS-only intervention, 2) 'SMS + pedometer' intervention or 3) 'usual care' control. The mHealth intervention involved SMS messages to parents; the 'SMS + pedometer' group also received a dog pedometer and personalised dog steps diary. Parent-reported measures were collected at baseline, 1- and 3-months post intervention. The primary outcome was weekly frequency of family dog walking and dog play; secondary outcomes were child attachment to the dog and feasibility of the intervention. A total of 150 children were randomised in staggered blocks to SMS-only (n = 50), 'SMS + pedometer' (n = 50) or usual care (n = 50). No differences were observed in family dog walking and dog play at 1-month. SMS-only children (OR 2.6, 95% CI 1.17, 5.83, P = 0.019) and all intervention children (OR 1.97, 95% CI 1.01, 3.86, P = 0.048) were more likely to increase total dog-facilitated physical activity (sum of family dog walking and dog play responses) at 3-months. The positive associations with total dog-facilitated physical activity disappeared (all P > 0.05) after adjusting for socio-demographic factors. The PLAYCE PAWS mHealth intervention did not significantly affect dog-facilitated physical activity in children. Given high levels of dog ownership in the community, SMS prompts could be a low-cost intervention to encourage more physical activity in children. Further research is needed to understand how increased interaction with the family dog impacts on children's overall physical activity and other health and development outcomes. ANZCTR, ACTRN12620000288921 , retrospectively registered on 4/3/2020.


Evaluation of suspected right ventricular pathology in the athlete.
Rigorous training remodels the heart of elite endurance athletes to produce the phenotype of the "athlete's heart." This remodeling, which advantages cardiac performance, creates challenges in the diagnosis of cardiac disorders within this population. This is particularly so for right ventricular pathologies because of the limited number of studies documenting the impact of training on right ventricular remodeling. Although arrhythmogenic right ventricular cardiomyopathy is the focus of this review, several other pathologies that may mimic arrhythmogenic right ventricular cardiomyopathy, including right ventricular outflow tract tachycardia, Wolff-Parkinson-White syndrome, Brugada syndrome, pulmonary embolism, cardiac sarcoidosis, myocarditis, and right ventricular infarction, are also included. In particular, the electrocardiographic findings for each condition are highlighted because this is the most informative and easily accessible diagnostic clinical tool.


Otolaryngologic findings in prepubertal obese children with sleep-disordered breathing.
To evaluate otolaryngologic findings in obese prepubertal children with sleep-disordered breathing. We prospectively evaluated 29 obese children referred by pediatric endocrinologist, complaining of snoring and without a history of nasal surgery or removal of the palatine tonsils and/or adenoids. Patients underwent ear, nose and throat (ENT) examination, endoscopy, measurements of weight, height, calculation of body mass index (BMI), assessment of BMI z-score and polysomnography, from which were divided into two groups: those with obstructive sleep apnea syndrome (nine children) and those with primary snoring (20 children). Then we proceeded to the statistical analysis of the data collected. The groups did not differ in age, gender, weight, height, BMI and BMI z-score. Among the findings of the ENT examination, the adenoid size was the only one that differed between the groups (p = 0.01). The evaluation of the adenoid size is an important in obese children with symptoms of sleep-disordered breathing and is related to the presence of obstructive sleep apnea syndrome.


Comparison of the prevalence, antibiotic resistance patterns, and biofilm formation ability of methicillin-resistant Staphylococcus pseudintermedius in healthy dogs and dogs with skin infections.
Staphylococcus pseudintermedius (S. pseudintermedius), found on dogs' skin and mucous membranes, can act as an opportunistic pathogen causing skin, ear, and other tissue infections. Due to the possibility of zoonotic transmission of them, it is necessary to investigate the prevalence of S. pseudintermedius, especially the antimicrobial-resistant strains, in pets. In this study, the prevalence, antimicrobial resistance patterns, and biofilm formation ability of methicillin-resistant S. pseudintermedius (MRSP) were investigated and compared in 50 healthy dogs and 50 dogs with skin infections. The prevalence of S. pseudintermedius was not significantly different between healthy dogs (40%) and dogs with skin infections (50%). No significant difference was found in the prevalence of MRSP between healthy dogs (12%) and dogs with skin infections (18%). A total of 81.8% of S. pseudintermedius isolates were biofilm producers. The frequencies of antibiotic resistance (except for gentamicin), multidrug resistance (MDR), and biofilm formation ability were not significantly different between S. pseudintermedius isolates of healthy dogs and dogs with skin infections. The frequencies of resistance to penicillin and tetracycline, MDR, and biofilm production abilities were significantly higher among MRSP than methicillin-susceptible S. pseudintermedius (MSSP). The frequency of oxacillin resistance was significantly higher among weak or moderate biofilm producers than non-biofilm producers. The frequency of resistance to erythromycin was significantly higher among moderate biofilm producers than non-biofilm producers or weak biofilm producers. High frequencies of biofilm-producer S. pseudintermedius isolates and their resistance to antibiotics can affect the success of treatment of infections caused by these strains.


Expression of cyclin E in placentas with hydropic change and gestational trophoblastic diseases: implications for the malignant transformation of trophoblasts.
Although much is known about the morphologic, cytogenetic, and clinical characters of gestational trophoblastic diseases, little information has appeared concerning the parameters related to their persistence or neoplastic transformation. Cell cycle alterations in tumor tissue were examined in this study in light of obvious changes in the clinical behavior of malignant cells. There is an increasing body of evidence suggesting that the abnormal expression of cyclins is considered one of the most important events in malignant transformation of various human cancers. Among these cell cycle regulators, the role of cyclin E in the neoplastic transformation of trophoblast populations has been poorly defined. Using formalin fixed, paraffin embedded trophoblastic tissues, the authors investigated the expression of cyclin E by immunohistochemistry in placentas with hydropic change and gestational trophoblastic diseases. The specimens examined included tissue from 29 patients with complete hydatidiform mole, 18 patients with partial hydatidiform mole, and 6 patients with choriocarcinoma after term pregnancy or abortion. The authors also studied four cases of hydropic abortion. The cyclin E indexes (CEI) were as follows: 25.7% +/- 6.2% for hydropic change, 35.3% +/- 12.7% for triploid partial moles, 42.2% +/- 13.1% for diploid/tetraploid complete moles, and 63.6% +/- 9.5% for choriocarcinomas. There was a significant difference in CEI between placentas with hydropic change and partial mole (P = 0.04) and placentas with hydropic change and complete mole (P = 0.003). Choriocarcinomas had significantly higher cyclin E expression compared with placentas, partial moles, and complete moles, respectively. A significant correlation between the expression of cyclin E and S-phase fraction was observed in gestational trophoblastic diseases (rank correlation coefficient = 0.45, P < 0. 05). The relation between cyclin E expression and proliferation was abrogated in placentas with hydropic change, suggesting that cyclin E up-regulation represents a genuine aberration. The results of this study were consistent with the concept that cyclin E overaccumulation may play an important role in the uncontrolled proliferation and neoplastic transformation of trophoblasts.


Oral Corticosteroid Treatment Patterns of Patients in the United States with Persistent Asthma.
Patients with poor asthma control may receive oral corticosteroid (OCS) therapy despite the risk for adverse effects. We assessed OCS use frequency and treatment patterns in patients with persistent asthma in the United States (US). We used the IBM MarketScan Commercial Claims and Encounters, Medicare Supplemental, and Medicaid Multistate Claims research databases to identify patients from January 1, 2012, to December 31, 2017, who were ≥12 years old, met the 2-year Healthcare Effectiveness Data and Information Set criteria for persistent asthma, and were continuously enrolled ≥6 months before (baseline) and ≥24 months after (follow-up) the persistent asthma index date. Patients were classified as high OCS use (defined as ≥450 mg of OCS prescribed within a 90-day period during follow-up), low use (use OCS but not meeting high use criteria), or no OCS use. We identified 435,675 patients, of whom 65% used OCS and 19% were classified as high OCS users at some point during follow-up. The annual prevalence of high OCS use ranged from 5.3% in 2013 to 7.6% in 2017. During the entire follow-up, high and low OCS users filled an average of 2.2 and 0.8 OCS prescriptions and received an average daily dosage of 2.2 and 0.3 mg, respectively. Once the patients became high OCS users, the average daily OCS dosage was relatively stable (5.1-7.1 mg) over 3 years. Patients with persistent asthma in the US have substantial exposure to OCS. OCS therapy should be considered carefully to avoid associated adverse effects.


Macroreentry as a mechanism of atrial-induced ventricular ectopic beats: a laboratory curiosity?
During electrophysiologic study in a patient, programmed stimulation of the atrium induced fixed coupled ventricular premature beats on the basis of intraventricular macroreentry. This type of macroreentry, which was reproducible, appears to have been merely a "laboratory curiosity" and never played a clinical role in this patient with chronic recurrent ventricular tachycardia.


Intranasal and Serum Gentamicin Concentration: Comparison of Three Topical Administration Protocols in Dogs.
Antimicrobials' topical administration efficacy has not been assessed in dogs with upper respiratory tract disease. The aim was to compare the concentration of gentamicin in nasal lavage fluid (NALF) and in serum after three topical protocols. This was a prospective crossover study of ten healthy dogs. Gentamicin was nebulized for a duration of 1 week, twice a day, for 10 min in the first protocol (10-min protocol) and for 3 min in the second protocol (3-min protocol), while the third protocol consisted of the administration of 0.25 mL of gentamicin in each nostril (drop protocol). Median concentrations of gentamicin in NALF were 9.39 µg/mL (8.12-19.97 interquartile range), 4.96 µg/mL (4.60-6.43) and 137.00 µg/mL (110.5-162.00) in the 10-min protocol, 3-min protocol and drop protocol, respectively. The result for the drop protocol was significantly higher than those of both nebulization protocols in NALF (p = 0.039). In serum, the gentamicin concentration was 0.98 µg/mL (0.65-1.53) and 0.25 µg/mL (0.25-0.44) in the 10-min and 3-min protocols, respectively. Gentamicin was not detected in the serum of seven out of ten dogs in the drop protocol, and gentamicin was significantly higher in the 10-min protocol compared to the drop protocol (p = 0.001). This study found that the 10-min, 3-min and drop protocols achieved superior concentrations in NALF compared to the minimum inhibitory concentration for gentamicin-sensitive bacteria, while remaining below the toxic values in blood.


Mental Health Symptoms Associated with Sexualized Drug Use (Chemsex) among Men Who Have Sex with Men: A Systematic Review.
Sexualized drug use (SDU), also known as chemsex, refers to the use of psychoactive substances for sexual purposes among men who have sex with men (MSM), which has been associated with mental health symptoms. The objective of this review is to systematically review the available evidence on mental health outcomes in MSM who use sexualized drugs. To prepare this systematic review, search strategies were developed and applied to the Web of Science, Science Direct, PubMed, and Scopus databases. A total of 117 articles were found, of which 12 were selected for the final review. Those MSM who practiced SDU were more likely to experience from depression, anxiety, or a substance dependence, although these results were not found in all the studies analyzed. Among those who practiced the administration of intravenous drugs (referred to as slamsex), the mental health symptoms were more severe. This systematic review contributes to a fuller understanding of the mental health symptoms present in MSM who consume drugs for sexual purposes. Greater uniformity in data collection instruments is required, as well as the need to conduct a more in-depth assessment of the psychosocial adjustment of people who practice chemsex.


Adsorption of organophosphorus malathion pesticide from aqueous solutions using nano-polypropylene-titanium dioxide composite: Equilibrium, kinetics and Optimization studies.
The purpose of this study was to investigate the applicability of the adsorption process of a persistent organophosphorus pesticide (malathion) from aqueous solutions by using titanium dioxide- polypropylene nanocomposite (Nano-PP/TiO2). The structure of Nano-PP/TiO2 was specified by field emission scanning electron microscopes (FE-SEM), fourier-transform infrared spectroscopy (FTIR), brunauer-emmett-teller (BET), and transmission electron microscope (TEM) technologies. Response surface methodology (RSM) was applied to optimize the adsorption of malathion onto Nano-PP/TiO2 and investigates the effects of various experimental parameters including contact time (5-60 min), adsorbent dose (0.5-4 g/l) and initial malathion concentration (5-20000 mg/l). Extraction and analysis of malathion were performed by dispersive liquid-liquid microextraction (DLLME) coupled with a gas chromatography, coupled with flame ionization detector (GC/FID). The isotherms obtained for Nano-PP/TiO2 revealed that it was a mesoporous material with a total pore volume of 2.06 cm3/g, average pore diameters of 2.48 nm and a surface area of 51.52 m2/g. The obtained results showed that the Langmuir type 2 was the best-fitted model for delegating the equilibrium data of isotherm studies with adsorption capacity of 7.43 mg/g, and pseudo-second-order type 1 for kinetic model. The optimized conditions to achieve the maximum removal (96%) were at a malathion concentration of 7.13 mg/L, contact time of 52 min and adsorbent dose of 0.5 g/L. Due to its efficient and appropriate function in adsorbing malathion from aqueous solutions, it was revealed that Nano-PP/TiO2 can be used as an effective adsorbent as well as in further studies.