A comparative study of voice complaints and risk factors for voice complaints in female student teachers and practicing teachers early in their career.
A cross-sectional questionnaire survey was performed to compare female student teachers (454 subjects; 1st to 4th year of training) and practicing teachers (82 female teachers; 1st to 4th year of teaching career) of primary education early in their career, with regard to risk factors perceived to be a negative influence on the voice, and the relative risk of the given risk factors for voice complaints. This enables the observation of whether there is a sudden increase or difference in the perceived risk factors after starting a professional teaching career. Additionally, the existence of a history of voice problems during training was questioned among the teachers. Teachers with voice complaints compared to teachers without voice complaints reported a history of voice complaints during their training (P =0.013). Teachers compared to student teachers reported more voice complaints at the moment and/or during the past year (P =0.002). The following data were obtained from student teachers and teachers reporting voice complaints. Only around a third of the subjects of both groups sought voice care (P =0.286-0.893). Risk factors were estimated in relation to voice complaints. Student teachers reported less frequently than teachers that stress (P =0.014), work pressure (P =0.003) and the composition of the class (P =0.013) have a negative influence on their voice. Student teachers reported less frequently than teachers that the number of people they communicate with (P <0.001) and the deterioration of their general physical condition (P =0.010) have a negative influence on their voice. Student teachers reported more frequently than teachers that environmental irritants (P <0.001) and humidity (P =0.020) of the classroom have a negative influence on their voice. Student teachers more than teachers were of the opinion that the attention paid to the voice during their training was sufficient (P <0.001). To test whether professional status (student teacher versus teacher) is an effect modifier for the risk factors, odds ratios (OR) were compared between the group of teachers and of student teachers (total group with and without voice complaints) to search for interactions between the risk factors and professional status. There is a significant difference in the pattern of risk factors for student teachers and teachers (P =0.010). There is an indication that vocal loading factors and environmental factors are more influential in student teachers and that there is a tendency for psycho-emotional factors to be more influential for teachers early in their career.


Mutant allele quantification reveals a genetic basis for TP53 mutation-driven castration resistance in prostate cancer cells.
The concept that human cancer is in essence a genetic disease driven by gene mutations has been well established, yet its utilization in functional studies of cancer genes has not been fully explored. Here, we describe a simple genetics-based approach that can quickly and sensitively reveal the effect of the alteration of a gene of interest on the fate of its host cells within a heterogeneous population, essentially monitoring the genetic selection that is associated with and powers the tumorigenesis. Using this approach, we discovered that loss-of-function of TP53 can promote the development of resistance of castration in prostate cancer cells via both transiently potentiating androgen-independent cell growth and facilitating the occurrence of genome instability. The study thus reveals a novel genetic basis underlying the development of castration resistance in prostate cancer cells and provides a facile genetic approach for studying a cancer gene of interest in versatile experimental conditions.


Pathophysiologic Response to Burns in the Elderly.
Over the last decades advancements have improved survival and outcomes of severely burned patients except one population, elderly. The Lethal Dose 50 (LD50) burn size in elderly has remained the same over the past three decades, and so has morbidity and mortality, despite the increased demand for elderly burn care. The objective of this study is to gain insights on why elderly burn patients have had such a poor outcome when compared to adult burn patients. The significance of this project is that to this date, burn care providers recognize the extreme poor outcome of elderly, but the reason remains unclear. In this prospective translational trial, we have determined clinical, metabolic, inflammatory, immune, and skin healing aspects. We found that elderly have a profound increased mortality, more premorbid conditions, and stay at the hospital for longer, p < 0.05. Interestingly, we could not find a higher incidence of infection or sepsis in elderly, p > 0.05, but a significant increased incidence of multi organ failure, p < 0.05. These clinical outcomes were associated with a delayed hypermetabolic response, increased hyperglycemic and hyperlipidemic responses, inversed inflammatory response, immune-compromisation and substantial delay in wound healing predominantly due to alteration in characteristics of progenitor cells, p < 0.05. In summary, elderly have substantially different responses to burns when compared to adults associated with increased morbidity and mortality. This study indicates that these responses are complex and not linear, requiring a multi-modal approach to improve the outcome of severely burned elderly.


Left atrial volume index predicts adverse events in asymptomatic moderate or severe aortic stenosis.
In aortic stenosis (AS), chronic pressure overload on left ventricle (LV) leads to LV hypertrophy, impaired relaxation, increased chamber stiffness, fibrosis and left atrial (LA) dilatation. An enlarged LA may be a marker of longstanding diastolic dysfunction (DD) and more advanced disease in AS. We aimed to assess the impact of LA volume index (LAVI) on events in patients with moderate or severe AS. A total of 324 patients (mean age 69 ± 13 years, 61% men) were included. LA volume was measured by biplane Simpson's method using apical four- and two-chamber views and indexed to body surface area. An increased LAVI was defined as > 34 ml/m2 . The mean EF was 64 ± 8%, LAVI 35 ± 14 ml/m2 and flow rate 244 ± 70 ml/s. The number of total events was 275 (85%): 243 (75%) aortic valve replacement and 32 (10%) deaths. Mean follow-up 23.7 ± 23.8 months (median 15.2 months). An increased LAVI (45% [n = 145]) was associated with adverse events (HR 1.86; 95% CI 1.24-2.82, p = 0.003) independent of age, smoking, diabetes, atrial fibrillation, LV ejection fraction, LV mass, aortic valve area, and low flow rate (<200 ml/s). In the same multivariate model, when increased LAVI was replaced by E/e' ratio ≥14 cm, no association was found between E/e' ratio ≥14 cm and adverse events (HR 1.18; 95% CI .78-1.78, p = 0.430). LAVI was an independent predictor of adverse events in patients with moderate or severe AS and preserved ejection fraction. Including LAVI in the risk assessment of AS patients may further improve risk stratification.


TEMPORARY REMOVAL: Orthodontic treatment for a patient with a unilateral cleft lip and palate and congenitally missing maxillary lateral incisors and left second premolar.
The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.


Patients' Adherence in the Maintenance Therapy of Children and Adolescents with Acute Lymphoblastic Leukemia.
Acute lymphoblastic leukemia (ALL) is the most common form of paediatric cancer. Maintenance therapy as last treatment phase includes oral chemotherapy with methotrexate (MTX) and mercaptopurine (6-MP), self- or parent-administered at home, given for about 1 ½ years, and qualified as decisive for an optimum therapy outcome. The aim of our study was to analyze factors influencing the adherence of patients with ALL undergoing maintenance therapy and their families. A multi-method study was undertaken between 11/2011 and 10/2014 with patients surveyed by the Hannover Medical School outpatient clinic, including a questionnaire survey and qualitative interviews with parents as well as blood samples of the patients. 33 questionnaires, 27 interviews and blood samples of 26 patients could be analyzed. Only one third of the blood samples showed concentrations of the 6-MP active metabolite within the therapeutic reference range. Parents named the clinical doctor as their main advisor on medication intake. 36% (12/33) of the participants stated that medication intake has not always occurred the way medication was prescribed. Drug formulation and drug intake information could be identified as determinants of adherence. Parents' problems to obtain information are partly caused by different study results concerning the correct timing of the drug intake and drug interactions with milk products. Parents' information on drug therapy should be more consistent and the pharmaceutical formulations have to be adapted to patients' needs to improve adherence and thereby the chance of long-term remission.


Management of acute asthma: a survey of hospital practice and comparison between thoracic and general physicians in Birmingham and Manchester.
The assessment and treatment of 140 randomly selected patients with acute asthma admitted to hospitals in Birmingham and Manchester in 1978 were studied. A detailed history of attack severity was recorded in just over half the case notes on admission (55%) and objective evidence of severity was recorded in a smaller number (measurement of airflow obstruction in 31% and arterial blood gases in 42%). Twenty-one (31%) thoracic patients and 33 (45%) general medical patients received aerosolized bronchodilators from metered-dose inhalers alone and 31% of all patients were given no inhaled bronchodilator drugs. Although the asthma was considered severe enough to require admission to hospital 37% were not given a course of corticosteroid therapy. Response to treatment was monitored by serial peak flow measurements in only 51% overall. Discharge therapy included a bronchodilator inhaler and oral corticosteroids in less than half (43%) of patients. There was no major difference in severity of asthma in patients admitted under the care of 'thoracic' or 'general' physicians but significant differences were found in their assessment and treatment. 'Thoracic' physicians more often measured severity and the response to treatment objectively. They prescribed inhaled (rather than intravenous) bronchodilator drugs more frequently and were more likely to discharge patients with a bronchodilator inhaler, oral corticosteroids, prophylactic therapy and an outpatient follow-up appointment.


Online Circuit Training Increases Adherence to Physical Activity: A Randomized Controlled Trial of Men with Obesity.
This study aimed to examine adherence to the weekly physical activity guidelines (≥150 min of aerobic activities at moderate-to-vigorous intensity and two or more sessions of strength training (yes or no)) and health outcomes during the COVID-19 pandemic for men living with obesity, 46 wk after being offered an online muscle-strengthening circuit program for 12 wk. Sixty men (age ≥19 yr) living with obesity (body fat percentage ≥25%) were randomly assigned to the intervention group ( n = 30) or the control condition ( n = 30) for 12 wk. The intervention group was offered an online circuit training, three sessions per week, whereas the control group received a website helping them to reach the physical activity guidelines. Adherence to the weekly physical activity guidelines was evaluated 46 wk after enrolling in the program using a heart rate tracker (Fitbit Charge 3) and an exercise log. Health outcomes (e.g., anthropometrics, body composition) were measured at baseline and after 12, 24, and 46 wk. The intervention group had higher adherence to physical activity guidelines at 46 wk (36.8%) than the control group (5.3%; P = 0.02). However, no difference in health outcomes was observed between participants in the intervention group compared with the control group after 12, 24, and 46 wk. Increasing adherence to exercise in men living with obesity is challenging. The proposed program increased adherence to the physical activity guidelines after about a year for men living with obesity; however, more studies are needed to understand how to improve health outcomes when following an online delivery exercise program in this population.


Ecm22 and Upc2 regulate yeast mating through control of expression of the mating genes PRM1 and PRM4.
Budding yeast mating is an excellent model for receptor-activated cell differentiation. Here we identify the related transcription factors Ecm22 and Upc2 as novel regulators of mating. Cells lacking both ECM22 and UPC2 display strong mating defects whereas deletion of either gene has no effect. Ecm22 and Upc2 positively regulate basal expression of PRM1 and PRM4. These genes are strongly induced in response to mating pheromone, which is also largely dependent on ECM22 and UPC2. We further show that deletion of PRM4 like PRM1 results in markedly reduced mating efficiency. Expression of PRM1 but not of PRM4 is also regulated by Ste12, a key transcription factor for mating. STE12 deletion lowers basal PRM1 expression, whereas STE12 overexpression strongly increases PRM1 levels. This regulation of PRM1 transcription is mediated through three Ste12-binding sites in the PRM1 promoter. Simultaneous deletion of ECM22 and UPC2 as well as mutation of the three Ste12-binding sites in the PRM1 promoter completely abolishes basal and pheromone-induced PRM1 expression, indicating that Ste12 and Ecm22/Upc2 control PRM1 transcription through distinct pathways. In summary, we propose a novel mechanism for budding yeast mating. We suggest that Ecm22 and Upc2 regulate mating through the induction of the mating genes PRM1 and PRM4.


Corrigendum: Interleaved Learning in Elementary School Mathematics: Effects on the Flexible and Adaptive Use of Subtraction Strategies.
[This corrects the article DOI: 10.3389/fpsyg.2019.00086.].


The hidden magnitude of polypharmacy: using defined daily doses and maximum licensed daily doses to measure antipsychotic load.
Background Antipsychotic polypharmacy ("polypharmacy") is the concurrent prescribing of more than one antipsychotic. It is widely practised, as reported in the literature, and is known to increase the risk of adverse outcomes for patients. Objective To quantify the prevalence and magnitude of polypharmacy in patients with schizophrenia or schizoaffective disorder and identify potential factors contributing to this practice. Setting Armadale Mental Health Service (a public inpatient and outpatient psychiatric facility in Perth, Western Australia). Method A retrospective, cross-sectional study was conducted, evaluating the medical records of adult (18-64 years old) patients fulfilling the established inclusion criteria in the period between August and December 2016. Data collected included the number and doses of antipsychotic(s) prescribed and documented rationale for polypharmacy. Defined daily doses and proportions of maximum licensed daily doses were calculated for all regularly prescribed antipsychotics and were evaluated as measures of antipsychotic load. Main Outcome Measure The percentage prevalence of antipsychotic polypharmacy; defined daily antipsychotic doses and proportions of maximum licensed daily doses. Results Seventy-seven patients were assessed, with a polypharmacy prevalence of 39.0%. Total defined daily doses ranged from 0.9 to 5.9 and maximum licensed daily doses from 0.4 to 2.3. Documented rationales for polypharmacy included poor symptom control, patient's preference, hesitancy to amend other prescribers' management plans, off-label antipsychotic indications and medication cross-titration. Conclusion Antipsychotic polypharmacy occurred in more than one-third of patients. Individual antipsychotics were typically prescribed at doses within the licensed range, however, the total proportion of combined maximum licensed doses and combined daily defined doses often exceeded 100%. Due to suboptimal documentation, prescribing rationale was unclear in the majority of cases. The magnitude of polypharmacy aims to foster a greater appreciation of the prescribed antipsychotic load, increasing clinician self-awareness of prescribing practices and facilitating future opportunities to optimise prescribing.


NADPH-dependent reductases of the dog lens.
The presence of several NADPH-dependent reductases has been observed in the dog lens. Applying the purification procedures of gel filtration, affinity chromatography and chromatofocusing to dog lens homogenates resulted in the purification of aldose reductase. This enzyme appeared similar to dog kidney aldose reductase in molecular weight, isoelectric point, kinetic properties, and susceptibility to inhibition by aldose reductase inhibitors. Evidence for the presence of trace amounts of aldehyde reductase in the dog lens was also observed, although this enzyme is not present in sufficient quantities for isolation and characterization. The presence of a labile third enzyme that is immunologically distinct from either aldose reductase or aldehyde reductase was also detected. This enzyme utilizes only glyceraldehyde as substrate and is not inhibited by aldose reductase inhibitors.


Clinical inertia is the enemy of therapeutic success in the management of diabetes and its complications: a narrative literature review.
Diabetes mellitus is a chronic disease characterized by high social, economic and health burden, mostly due to the high incidence and morbidity of diabetes complications. Numerous studies have shown that optimizing metabolic control may reduce the risk of micro and macrovascular complications related to the disease, and the algorithms suggest that an appropriate and timely step of care intensification should be proposed after 3 months from the failure to achieve metabolic goals. Nonetheless, many population studies show that glycemic control in diabetic patients is often inadequate. The phenomenon of clinical inertia in diabetology, defined as the failure to start a therapy or its intensification/de-intensification when appropriate, has been studied for almost 20 years, and it is not limited to diabetes care, but also affects other specialties. In the present manuscript, we have documented the issue of inertia in its complexity, assessing its dimensions, its epidemiological weight, and its burden over the effectiveness of care. Our main goal is the identification of the causes of clinical inertia in diabetology, and the quantification of its social and health-related consequences through the adoption of appropriate indicators, in an effort to advance possible solutions and proposals to fight and possibly overcome clinical inertia, thus improving health outcomes and quality of care.


Development, optimization, validation and application of faster gas chromatography - flame ionization detector method for the analysis of total petroleum hydrocarbons in contaminated soils.
This paper presents an important new approach to improving the timeliness of Total Petroleum Hydrocarbon (TPH) analysis in the soil by Gas Chromatography - Flame Ionization Detector (GC-FID) using the CCME Canada-Wide Standard reference method. The Canada-Wide Standard (CWS) method is used for the analysis of petroleum hydrocarbon compounds across Canada. However, inter-laboratory application of this method for the analysis of TPH in the soil has often shown considerable variability in the results. This could be due, in part, to the different gas chromatography (GC) conditions, other steps involved in the method, as well as the soil properties. In addition, there are differences in the interpretation of the GC results, which impacts the determination of the effectiveness of remediation at hydrocarbon-contaminated sites. In this work, multivariate experimental design approach was used to develop and validate the analytical method for a faster quantitative analysis of TPH in (contaminated) soil. A fractional factorial design (fFD) was used to screen six factors to identify the most significant factors impacting the analysis. These factors included: injection volume (μL), injection temperature (°C), oven program (°C/min), detector temperature (°C), carrier gas flow rate (mL/min) and solvent ratio (v/v hexane/dichloromethane). The most important factors (carrier gas flow rate and oven program) were then optimized using a central composite response surface design. Robustness testing and validation of model compares favourably with the experimental results with percentage difference of 2.78% for the analysis time. This research successfully reduced the method's standard analytical time from 20 to 8min with all the carbon fractions eluting. The method was successfully applied for fast TPH analysis of Bunker C oil contaminated soil. A reduced analytical time would offer many benefits including an improved laboratory reporting times, and overall improved clean up efficiency. The method was successfully applied for the analysis of TPH of Bunker C oil in contaminated soil.


PARP-1 modifies the effectiveness of p53-mediated DNA damage response.
The tumour suppressor protein p53 plays a key role in the cell's decision to arrest the cell cycle or undergo apoptosis following a genotoxic insult. p53 is stabilized and activated after DNA damage, however the cascade of events signalling from DNA lesions to p53 stabilization and activation is still controversial. Poly (ADP-ribosylation) of different nuclear acceptors by PARP-1 is an early event when a single strand DNA lesion is produced. We present here evidences that interplay between PARP-1 and p53 is dependent on the type of damage induced to DNA. Primary mouse embryonic fibroblasts derived from parp-1 -/- mice exhibited decreased p53 accumulation and activation following gamma-irradiation compared to parp-1 proficient cells. On the other hand, treatment with the single alkylating agent 2'-methyl-2'-nitrose-urea (MNU), resulted in the rapid and sustained accumulation and activation of p53 in parp-1-deficient cells, while very little accumulation was observed in parp-1 +/+ cells. After IR, the turnover of the p53 inhibitory protein MDM-2 is perturbed and the level of phosphorylation of p53 at serine-15 is blunted in parp-1 -/- cells. PARP-1 is determinant in the cytotoxic response to alkylating agents but only partially contributes to radiation-induced cell killing, as determined by colony forming assay. Altogether, these results suggest that PARP-1 participates in the p53 response following irradiation, resides upstream of p53 and indirectly modulates the level of phosphorylation of key substrates in this pathway while treatment with MNU results in an enhanced p53-mediated response in parp-1-null cells.


Astrocytes and retrograde degeneration of nigrostriatal dopaminergic neurons in Parkinson's disease: removing axonal debris.
The dopaminergic nigrostriatal neurons (DA cells) in healthy people present a slow degeneration with aging, which produces cellular debris throughout life. About 2%-5% of people present rapid cell degeneration of more than 50% of DA cells, which produces Parkinson's disease (PD). Neuroinflammation accelerates the cell degeneration and may be critical for the transition between the slow physiological and the rapid pathological degeneration of DA cells, particularly when it activates microglial cells of the medial forebrain bundle near dopaminergic axons. As synaptic debris produced by DA cell degeneration may trigger the parkinsonian neuroinflammation, this study investigated the removal of axonal debris produced by retrograde degeneration of DA cells, paying particular attention to the relative roles of astrocytes and microglia. Rats and mice were injected in the lateral ventricles with 6-hydroxydopamine, inducing a degeneration of dopaminergic synapses in the striatum which was not accompanied by non-selective tissue damage, microgliosis or neuroinflammation. The possible retrograde degeneration of dopaminergic axons, and the production and metabolization of DA-cell debris were studied with immunohistochemical methods and analyzed in confocal and electron microscopy images. The selective degeneration of dopaminergic synapses in the striatum was followed by a retrograde degeneration of dopaminergic axons whose debris was found within spheroids of the medial forebrain bundle. These spheroids retained mitochondria and most (e.g., tyrosine hydroxylase, the dopamine transporter protein, and amyloid precursor protein) but not all (e.g., α-synuclein) proteins of the degenerating dopaminergic axons. Spheroids showed initial (autophagosomes) but not late (lysosomes) components of autophagy (incomplete autophagy). These spheroids were penetrated by astrocytic processes of the medial forebrain bundle, which provided the lysosomes needed to continue the degradation of dopaminergic debris. Finally, dopaminergic proteins were observed in the cell somata of astrocytes. No microgliosis or microglial phagocytosis of debris was observed in the medial forebrain bundle during the retrograde degeneration of dopaminergic axons. The present data suggest a physiological role of astrocytic phagocytosis of axonal debris for the medial forebrain bundle astrocytes, which may prevent the activation of microglia and the spread of retrograde axonal degeneration in PD.


PE-STOP: A versatile tool for installing nonsense substitutions amenable for precise reversion.
The rapid advances in genome editing technologies have revolutionized the study of gene functions in cell or animal models. The recent generation of double-stranded DNA cleavage-independent base editors has been suitably adapted for interrogation of protein-coding genes on the basis of introducing premature stop codons or disabling the start codons. However, such versions of stop/start codon-oriented genetic tools still present limitations on their versatility, base-level precision, and target specificity. Here, we exploit a newly developed prime editor (PE) that differs from base editors by its adoption of a reverse transcriptase activity, which enables incorporation of various types of precise edits templated by a specialized prime editing guide RNA. Based on such a versatile platform, we established a prime editing-empowered method (PE-STOP) for installation of nonsense substitutions, providing a complementary approach to the present gene-targeting tools. PE-STOP is bioinformatically predicted to feature substantially expanded coverage in the genome space. In practice, PE-STOP introduces stop codons with good efficiencies in human embryonic kidney 293T and N2a cells (with medians of 29% [ten sites] and 25% [four sites] editing efficiencies, respectively), while exhibiting minimal off-target effects and high on-target precision. Furthermore, given the fact that PE installs prime editing guide RNA-templated mutations, we introduce a unique strategy for precise genetic rescue of PE-STOP-dependent nonsense mutation via the same PE platform. Altogether, the present work demonstrates a versatile and specific tool for gene inactivation and for functional interrogation of nonsense mutations.


Varicella pneumonia in an immunocompetent child: A case report.
Varicella-zoster virus (VZV) is a type of herpes virus that causes varicella (primary infection) and herpes zoster/shingles (due to reactivation of latent infection). Usually a benign and a self-limited illness, the illness sometimes can result in severe complications in both immunocompetent and immunocompromised persons. Varicella Pneumonia as a complication of herpes zoster is a rare event, with reports primarily concerning immunocompromised individuals. Here we report a 14-year-old female who developed a secondary bacterial infection of the skin lesions and varicella pneumonia associated with VZV infection. The patient presented with multiple painful vesicles that later turned into pustular lesions over the right cheek with erosions and hemorrhagic crusting. Swelling involving the right half of both upper and lower lips was present. She developed a fever, cough, and shortness of breath after two days of the presence of vesico-pustular lesions. A diagnosis of Pneumonia was made based on symptoms of fever and cough and findings on chest x-ray. This case highlights, though rare, varicella pneumonia has a high rate of respiratory failure, but early diagnosis with prompt administration of antiviral medications can improve outcomes.


The basic reproductive ratio of the 2022 outbreak of the monkey pox virus disease for the United Kingdom, Canada, Brazil, the United Arab Emirates, and Nigeria.
A recent outbreak of the monkey pox virus disease (MPVD) started to spread over the world before the second half of the 2022 year. This outbreak of the monkey pox virus disease is known as the 2022 outbreak of the monkey pox virus disease. The monkey pox virus disease is a type of the pox disease similar to the human one. This disease is an endemic in some African countries; however, a new spreading of this disease started to appear in other countries, such as the Spain, brazil, Greece, the United Kingdom, and Portugal, Australia, and the USA. As of the end of September 2022, the MPVD spread over than 107 countries over the world. This study focuses on the employing of the simplest model of the diseases forecasting which is SIRD model for the finding of the basic reproductive ratio of the monkey pox virus disease in multiple countries over the world where the disease spreads. The model takes into accounts the number of the susceptible people, the number of the infectious people, the number of the recovered people, and the number of the deceased people. Based on the results of the SIRD model coefficients, we find that the basic reproductive ratio values of the recent spreading of the monkey pox virus disease are 1.3274 for the United Kingdom where the first case of the disease was recorded, 1.0714 for the United Arab Emirates, 1.0866 for Nigeria, 1.5589 for Brazil, and 1.3610 for Canada. We find that the average value of the basic reproductive ratio of the 2022 outbreak of the monkey pox virus disease is about 1.2809. This important result of our calculations predicts that the 2022 outbreak of the monkey pox virus disease is turned into pandemic over the world. The things which confirm this result, based on our calculations, are the values of the basic reproductive ratio of the 2022 outbreak of the disease in the considered countries from multiple continents where all the values of the basic reproductive ratio are bigger than one. From this point, the counties over the world must apply multiple procedures for limiting the spreading of the monkey pox virus disease.


Rapid decline in MyHC I(β) mRNA expression in rat soleus during hindlimb unloading is associated with AMPK dephosphorylation.
Inactivation of a skeletal muscle results in slow to fast myosin heavy chain (MyHC) shift. AMP-activated protein kinase (AMPK) can be implicated in the regulation of genes encoding the slow MyHC isoform. Here we report that AMPK dephosphorylation after 24 h of mechanical unloading can contribute to histone deacetylase (HDAC) nuclear translocation; activation of AMPK prevents HDAC4 nuclear accumulation after 24 h of unloading and AMPK dephosphorylation inhibits slow MyHC expression following 24 h of unloading. Our data indicate that AMPK dephosphorylation during the first 24 h of mechanical unloading has a significant impact on the expression of MyHC isoforms in rat soleus causing a decrease in MyHC I(β) pre-mRNA and mRNA expression as well as MyHC IIa mRNA expression. One of the key events that occurs during skeletal muscle inactivation is a change in myosin phenotype, i.e. increased expression of fast isoforms and decreased expression of the slow isoform of myosin heavy chain (MyHC). It is known that calcineurin/nuclear factor of activated T-cells and AMP-activated protein kinase (AMPK) can regulate the expression of genes encoding MyHC slow isoform. Earlier, we found a significant decrease in phosphorylated AMPK in rat soleus after 24 h of hindlimb unloading (HU). We hypothesized that a decrease in AMPK phosphorylation and subsequent histone deacetylase (HDAC) nuclear translocation can be one of the triggering events leading to a reduced expression of slow MyHC. To test this hypothesis, Wistar rats were treated with AMPK activator (AICAR) for 6 days before HU as well as during 24 h of HU. We discovered that AICAR treatment prevented a decrease in pre-mRNA and mRNA expression of MyHC I as well as MyHC IIa mRNA expression. Twenty-four hours of hindlimb suspension resulted in HDAC4 accumulation in the nuclei of rat soleus but AICAR pretreatment prevented this accumulation. The results of the study indicate that AMPK dephosphorylation after 24 h of HU had a significant impact on the MyHC I and MyHC IIa mRNA expression in rat soleus. AMPK dephosphorylation also contributed to HDAC4 translocation to the nuclei of soleus muscle fibres, suggesting an important role of HDAC4 as an epigenetic regulator in the process of myosin phenotype transformation.


DNA linearization through confinement in nanofluidic channels.
Stretching DNA has emerged as a vital process for studying the physical and biological properties of these molecules. Over the past decade, there has been increasing research interest in utilizing nanoscale fluidic channels to confine and stretch single DNA molecules. Nanofabricated systems for linearizing DNA have revealed new and important insights into the conformation changes of DNA molecules. They also have emerged as innovative techniques for efficiently separating DNA molecules based on size and for physically mapping genetic information along the genome. This review describes physical theories of DNA linearization, current DNA stretching techniques based on nanofabricated channels, and breakthroughs resulting from the use of nanofluidic channels for DNA linearization.


Studies on the bovine brain pyruvate dehydrogenase complex using the antibodies against kidney enzyme complex.
Pyruvate dehydrogenase complex (PDHC) was purified from bovine kidney with a specific activity of 12-16 mumol of NADH or acetyl-CoA formed/min/mg protein. The four peptides comprising its three catalytic components were separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Rabbit antibodies against this highly purified PDHC (anti-PDHC) exhibited similar binding affinity to the phospho-PDHC as it did to the PDHC antigen. To test whether there exist brain isozymes of PDHC differing from kidney enzyme, which has been extensively characterized, the PDHCs in bovine brain and kidney were compared using this anti-PDHC. The PDHC activities in the brain and kidney mitochondrial extracts were inhibited to the same degree by varying amounts of anti-PDHC. Brain PDHC was precipitated with the anti-PDHC and resolved by SDS-PAGE. The four brain PDHC peptides isolated immunochemically with anti-PDHC had the same sizes as the kidney PDHC peptides. These PDHC peptides from kidney and brain were further compared by their peptide fragment patterns, which were generated by partial proteolysis with Staphylococcus aureus V8 protease or by CNBr and resolved by SDS-PAGE. The peptide patterns generated with the former method indicated that the alpha and beta peptides of the pyruvate dehydrogenase (E1) component and the peptide of dihydrolipoyl transacetylase (E2) component of kidney PDHC were very similar to the corresponding peptides immunologically isolated from brain. The peptide patterns generated with CNBr further confirmed that the beta E1 and E2 peptides of kidney PDHC were similar to the corresponding peptides from brain.


Synthesis of novel hybrid hetero-steroids: Molecular docking study augmented anti-proliferative properties against cancerous cells.
Hetero-steroids, hybrid anticancer agents, have received much interest in view of their numerous and promising biological activities. In this study, a novel class of hetero-steroids were synthesized, analytical and spectral data proved the validity of the novel synthesized steroid derivatives. The cytotoxicity of the synthesized compounds 2, 5, 6, 7, 10, 11, 12, 14, 15, 17 were evaluated using human hepatocellular carcinoma cell lines (HepG2 and Huh-7) and non-small cell lung cancer (A549) cell lines. The synthesized compounds reported a remarkable gradual decrease in the cell viability of the three tested cancer cell lines. It was observed that compounds 2 and 12 had the lowest IC50s and the highest cytotoxic effects against all tested cell lines. As attempt to explain the cytotoxic activity achieved by the tested compounds in the in vitro study, molecular simulation was done to reveal the activity of the tested compounds against four different proteins (CDK2, CYP19, JAK2, and BCL2) which are highly implicated in cancer regulation and progression. We found that compound 2, and 12 were the best docked compounds against all tested receptors, which was indicated by lowest binding energy compared to reference ligand. Interestingly enough, our molecular study was in agreement with the cytotoxic activity. As future prospective, we are recommending further study on compounds 2, and 12 against the four different proteins to prove their mode of action.


Airborne Food Allergen and Aeroallergen Levels in Health Care Settings: An Unaccounted for but Potentially Relevant Source of Exposure?
Exposure to airborne allergens of biological origin is associated with the development and exacerbation of allergic asthma and rhinitis. Assessment of allergen exposure in health care facilities may improve monitoring of hygiene and surveillance of specific allergens that can cause symptoms in sensitized persons. Objective: To assess concentrations of airborne food and aeroallergens in various health care settings in Portugal. Dust was vacuumed from primary health care centers in Lisbon and from the emergency department, day hospital, internal medicine ward, operating room, and outpatient clinic of a university central hospital in Porto. Samples were sieved, weighed, and extracted, and concentrations of Nbos d 5, Cor a 9, Gal d 2, Ara h 3, Ara h 6, Der p 1, Fel d 1, Can f 1, Bla g 2, Alt a 1, and Phl p 5 were determined using a multiplex array for allergens (MARIA). All airborne food and aeroallergens were found in at least 1 sampled area, except for Alt a 1. Levels of Der p 1 and Fel d 1 ranged from 13.0 μg/g to 971.0 μg/g and from 7.0 μg/g to 4618.8 μg/g, respectively. Higher levels of food allergens were found in the emergency department (Nbos d 5, 16 034.0 μg/g; and Cor a 9, 10 649.5 μg/g). Except for the operating room, exposure levels for dust mite and cat and dog dander in health care facilities were above the values associated with sensitization and allergic asthma or rhinitis symptoms in sensitized persons.


Detection of the oil-producing microalga Botryococcus braunii in natural freshwater environments by targeting the hydrocarbon biosynthesis gene SSL-3.
The green microalga Botryococcus braunii produces hydrocarbon oils at 25-75% of its dry weight and is a promising source of biofuel feedstock. Few studies have examined this species' ecology in natural habitats, and few wild genetic resources have been collected due to difficulties caused by its low abundance in nature. This study aimed to develop a real-time PCR assay for specific detection and quantification of this alga in natural environments and to quantify spatiotemporal variations of wild B. braunii populations in a tropical pond. We designed PCR primers toward the hydrocarbon biosynthesis gene SSL-3 and examined amplification specificity and PCR efficiency with 70 wild strains newly isolated from various environments. The results demonstrated that this PCR assay specifically amplified B. braunii DNA, especially that of B-race strains, and can be widely used to detect wild B. braunii strains in temperate and tropical habitats. Field-testing in a tropical pond suggested a diurnal change in the abundance of B. braunii in surface water and found B. braunii not only in surface water, but also at 1-1.5 m deep and in bottom sediments. This method can contribute to efficient genetic resource exploitations and may also help elucidate the unknown ecology of B. braunii.


Special observation and older persons with dementia/delirium: a disappointing literature review.
In gerontological practice, special observation is a known nursing activity across different settings. The group that possibly are most effected by this intervention are older persons with dementia and/or delirium. The research literature about special observations in the mental health field is small, more disappointingly there appears to be little published literature about special observations in regard to older persons with dementia and/or delirium. The aims of this study are to (i) establish the state of current published research on special observations in regard to older persons with dementia and/or delirium and (ii) make recommendations for research and practice. A literature review. Most literature pertains to adult mental health practice and services. Themes were generated and discussed in relation to gerontological practice. This review has established there is variance in the usage of the terms 'special observation' and 'constant observation'. It concludes that there is no published research on special or constant observations in relation to older people with dementia/delirium or the purpose of this activity. There is therefore a clear need to establish a research base in the topic. Given the limited evidence, practitioners and managers need to be cautious when writing and implementing policies about special observation. However, until gerontological research is improved, research from mental health nursing will need to be drawn on with caution and the purpose of special observation determined locally. To be of therapeutic value and to be cost effective, special observation should be seen as a skilled nursing intervention and not a passive 'watching' or 'sitter' activity.


Corrigendum to "Optimization of cacao beans fermentation by native species and electromagnetic fields" [Heliyon 9(4) April 2023 e15065].
[This corrects the article DOI: 10.1016/j.heliyon.2023.e15065.].


Uptake of exogenous fluorescent Di-I by intact junctional epithelium of adult rats allows retrograde labeling of trigeminal sensory neurons.
Junctional epithelium (JE) is the special attachment tissue between gingiva and teeth, and it is well innervated by sensory nerve fibers. We have found that the fluorescent carbocyanine dye, Di-I, can penetrate quickly into intact JE and spread into connective tissue. Di-I containing neurons in trigeminal ganglion were found at 3-7 days and were mostly gone by 3 weeks. We conclude that substances such as Di-I can penetrate through permeable epithelia such as intact JE where they are picked up by sensory nerve fibers and carried to nerve cell bodies.


Homocysteine-lowering therapy and carotid intima-media thickness in renal transplant recipients.
The aim of this study was to document, in hyperhomocysteinemic renal transplant recipients, the effect of vitamin supplementation on carotid intima-media thickness (cIMT). Fifty-six hyperhomocysteinemic stable renal transplant recipients were randomly assigned to either vitamin supplementation (group A) or placebo treatment (group B). All patients underwent high-resolution B mode ultrasound to measure IMT of common carotid arteries before and after 6 months of vitamin supplementation. In group A, cIMT significantly decreased after treatment, whereas no significant changes were observed in group B. In conclusion, our results demonstrate a beneficial effect of the treatment of hyperhomocysteinemia by vitamin supplementation on an early sign of atherosclerosis in a group of renal transplant recipients.


An immunochromatographic assay utilizing magnetic nanoparticles to detect major peanut allergen Ara h 1 in processed foods.
This study describes an immunomagnetic nanoparticle (IMNP)-based lateral flow assay (LFA) for detecting the major peanut allergen Ara h 1. We developed a clearly specific method in identifying peanut from ten other seeds and nuts, and a good visual limit of detection (vLOD) of 0.01 μg/mL Ara h 1 in PBS. PBS that contains 1 M NaCl and 2% Tween 20 was determined to be the optimal extraction buffer for isolating Ara h 1 from cookie, milk and chocolate with vLOD values of 0.5 μg/g, 0.5 μg/mL, and 1 μg/g, respectively. Forty two processed foods were simultaneously analyzed using this method and an AOAC-approved ELISA kit. The specificity and sensitivity of this assay were thus determined to be 100 and 95%, respectively. This new IMNP-based LFA has potential as a rapid tool for screening processed foods for Ara h 1 residues.


Inhibitory effect of resveratrol on swimming motility and adhesion ability against Salmonella enterica serovar Typhimurium infection.
Salmonella enterica serovar Typhimurium (S. typhimurium) is a common Gram-negative foodborne pathogen that threatens public health and hinders the development of livestock industry. Resveratrol, an important component in grape fruits and seeds, has been shown to possess multiple biological activities, but its potential effects on S. typhimurium-mediated virulence have been rarely reported. In this study, we investigated the effect of resveratrol on S. typhimurium flagella -mediated virulence. The results showed that resveratrol significantly reduced the transcription of flagella genes and swimming motility of S. typhimurium, and also inhibited the transcription of T3SS-related virulence genes with varying degrees inhibiting bacterial growth. Simultaneously, resveratrol significantly reduced the adhesion of S. typhimurium to HeLa cells. Unfortunately, resveratrol does not improve the survival rate of S. typhimurium-infected mice, but it reduces the bacterial load in the liver and spleen of infected mice, and it also has a certain degree of anti-inflammatory activity. In summary, these results indicated that resveratrol has the potential to be developed as an alternative drug or antibacterial agent to prevent Salmonella infection.


Effect of a pre-emptive 2-hour session of high-flow nasal oxygen on postoperative oxygenation after major gynaecologic surgery: a randomised clinical trial.
We aimed at determining whether a 2-h session of high-flow nasal oxygen (HFNO) immediately after extubation improves oxygen exchange after major gynaecological surgery in the Trendelenburg position in adult female patients. In this single-centre, open-label, randomised trial, patients who underwent major gynaecological surgery were randomised to HFNO or conventional oxygen treatment with a Venturi mask. The primary outcome was the Pao2/FiO2 ratio after 2 h of treatment. Secondary outcomes included lung ultrasound score, diaphragm thickening fraction, dyspnoea, ventilatory frequency, Paco2, the percentage of patients with impaired gas exchange (Pao2/FiO2 ≤40 kPa) after 2 h of treatment, and postoperative pulmonary complications at 30 days. A total of 83 patients were included (42 in the HFNO group and 41 in the conventional treatment group). After 2 h of treatment, median (inter-quartile range) Pao2/FiO2 was 52.9 (47.9-65.2) kPa in the HFNO group and 45.7 (36.4 -55.9) kPa in the conventional treatment group (mean difference 8.7 kPa [95% CI: 3.4 to 13.9], P=0.003). The lung ultrasound score was lower in the HFNO group than in the conventional treatment group (9 [6-10] vs 12 [10-14], P<0.001), mostly because of the difference of the score in dorsal areas (7 [6-8] vs 10 [9-10], P<0.001). The percentage of patients with impaired gas exchange was lower in the HFNO group than in the conventional treatment group (5% vs 37%, P<0.001). All other secondary outcomes were not different between groups. In patients who underwent major gynaecological surgery, a pre-emptive 2-h session of HFNO after extubation improved postoperative oxygen exchange and reduced atelectasis compared with a conventional oxygen treatment strategy. NCT04566419.


The role of HLA DQ2 and DQ8 in dissecting celiac-like disease in common variable immunodeficiency.
Gastrointestinal manifestations are frequent in patients with common variable immunodeficiency (CVID), and some of the patients present with celiac-like features. Diagnosing celiac disease (CD) in CVID however is challenging, as autoantibody detection and histopathology of the small intestine cannot reliably discriminate between classic CD and a celiac-like disease in these individuals. For the development of classic gluten-sensitive CD a certain HLA haplotype involving the loci DQA1* and DQB1* and encoding two different HLA DQ heterodimers is the prerequisite. We aimed to determine the frequency of these haplotypes in CVID patients with suspected CD. Furthermore, we report on autoimmune manifestations and the lymphocyte phenotype in these patients. By retrospective analysis data on gastrointestinal symptoms, diet, concurrent autoimmune diseases, and routine laboratory values were collected. CVID patients were classified according to their B-cell phenotype. Expression of HLA-DQA1* and HLA-DQB1* alleles were determined by genetic analysis. Twenty out of 250 CVID patients presented with a clinical phenotype resembling celiac disease. Four (20%) out of these CVID patients carried the CD-associated HLA DQ2.5 or DQ8 heterodimer, while HLA DQ2.5 was present in 100% of a CD control cohort. Gluten-free diet (GFD) resulted in a clinical and histological response in two out of four patients with HLA high-risk alleles for CD. The response could not be assessed in the remaining two patients, as these patients did not adhere sufficiently long to GFD. The percentage of autoimmune manifestations other than CD was high (50%) in CVID patients presenting with a CD-like enteropathy, and most of these patients had an expansion of B-cells with low expression of CD21 (CD21low B-cells). In CVID patients with suspected celiac disease typing of the HLA loci DQA1 and DQB1 can help to identify those that have a genetic susceptibility for CD. In CVID patients with a celiac-like phenotype but negative for CD-associated HLA-DQ markers, an autoimmune enteropathy (AIE) as part of an extended autoimmune dysregulation needs to be considered. This has important implications for further diagnostics and therapy of these patients.


Toxic oil syndrome and eosinophilia-myalgia syndrome: May 8-10, 1991, World Health Organization meeting report.
In May 1991, researchers and clinicians from throughout the world met at a workshop sponsored by the Regional Office for Europe of the World Health Organization in collaboration with the Fondo de Investigación Sanitaria, Spain, and the U.S. Food and Drug Administration, National Institutes of Health, National Institutes of Mental Health, and Centers for Disease Control and Prevention to share information about two very similar diseases--toxic oil syndrome and eosinophilia-myalgia syndrome. In this paper the interpretation of conference proceedings is presented, current knowledge of the two disorders is summarized, and some possible areas for future research are mentioned. Toxic oil syndrome and eosinophilia-myalgia syndrome have many similarities. Both are related to consumer products that were presumed to be safe but have been found to have numerous trace contaminants, many of which remain to be identified, including the etiologic agents of both disorders. Both illnesses affect patients clinically by causing intense, incapacitating myalgias and a marked peripheral eosinophilia. Other rheumatologic manifestations are common in both, including arthralgias, sicca syndrome, scleroderma-like skin changes, carpal tunnel syndrome, and joint contractures. No clinical or laboratory feature has been found to be pathognomonic of either disease, and accurate diagnosis rests on the clinical judgment of the attending physician. Deaths have occurred in both diseases, and the cumulative mortality for each is approximately 2.5% for the first 2 years. Long-term complications include pulmonary hypertension, peripheral neuropathies, and joint contractures. Although treatment with corticosteroids has resulted in significant symptomatic relief in persons with either disorder, it does not alter the clinical course or long-term outcome. Research into the etiologic agents, preferred treatments, and ways to avoid similar problems in the future is needed.


Methodology and study population of the second Swiss national community survey of functioning after spinal cord injury.
Descriptive study of the second community survey of the Swiss Spinal Cord Injury Cohort Study (Survey 2017) conducted between 03/2017 and 03/2018. To describe the methodology, recruitment results, characteristics of participants and non-participants, and non-response of the Survey 2017. Community. Description of the sampling strategy and sampling frame. Recruitment results and characteristics of participants and non-participants of the two Survey 2017 questionnaire modules were analyzed using descriptive statistics. Determinants of survey participation were examined using multivariable logistic regression, and the impact of non-response bias on survey results was evaluated using inverse-probability weighting. Out of 3959 persons who met the eligibility criteria, 1530 responded to module 1 (response rate 38.6%) and 1294 to module 2 (response rate 32.7%) of the Survey 2017. Of the 4493 invited persons, 1549 had participated in the first SwiSCI community survey conducted in 2012/2013. Of these, 1332 were invited to the Survey 2017 and 761 participated in module 1 (response rate 58.9%) and 685 in module 2 (response rate 53.1%). The majority of module 1 participants were male (71.2%, 95% CI: 68.9, 73.5), with a median age of 57 (IQR: 46.0, 67.0) years and incomplete paraplegia (41.9%, 95% CI: 39.3, 44.5). Survey non-response was higher in the oldest age group, among females, and those with tetraplegia. The design of the Survey 2017 was successful in recruiting a substantial proportion of the SCI source population in Switzerland. To counteract survey non-response, survey weights may be applied to subsequent analyses. none.


Molecular pathways in peritoneal fibrosis.
Peritoneal dialysis (PD) is a renal replacement therapy for patients with end-stage renal disease that is equivalent to hemodialysis with respect to adequacy, mortality, and other outcome parameters, yet providing superior quality-of-life measures and cost savings. However, long-term usage of the patient's peritoneal membrane as a dialyzer filter is unphysiological and leads to peritoneal fibrosis, which is a major factor of patient morbidity and PD technique failure, resulting in a transfer to hemodialysis or death. Peritoneal fibrosis pathophysiology involves chronic inflammation and the fibrotic process itself. Frequently, inflammation precedes membrane fibrosis development, although a bidirectional relationship of one inducing the other exists. This review aims at highlighting the histopathological definition of peritoneal fibrosis, outlining the interplay of fibrosis, angiogenesis and epithelial-to-mesenchymal transition (EMT), delineating important fibrogenic pathways involving Smad-dependent and Smad-independent transforming growth factor-β (TGF-β) as well as connective tissue growth factor (CTGF) signaling, and summarizing historic and recent studies of inflammatory pathways involving NOD-like receptor protein 3 (NLRP3)/interleukin (IL)-1β, IL-6, IL-17, and other cytokines.


Plasma fibronectin concentrations in healthy newborns and in children.
Plasma fibronectin (FN) concentrations were measured by an immunonephelometric method in cord blood from 76 healthy newborns (45 full term and 31 preterm), in 181 healthy children, from 1 month-15 years old, divided by age into seven groups and in 81 control adults. FN levels in newborns were 35% of those of adults. There was no difference between plasma FN in term and preterm (gestational age greater than 30 weeks) infants. Preterm newborns below the gestational age of 30 weeks showed particularly low FN levels. No clear correlation was seen with birth weight. In the child population, a strong increase in FN values was noted in the first 6 months of life, rising to 65% of the normal adult values. No further increase occurred until puberty.


Ambulatory gastric lavages provide better yields of Mycobacterium tuberculosis than induced sputum in children with intrathoracic tuberculosis.
To compare mycobacterial yield by induced sputum (IS) and gastric lavage (GL), performed on an ambulatory basis in children with probable intrathoracic tuberculosis. Diagnostic accuracy study. Two tertiary care hospitals in Delhi, India. Children aged 6 months to 15 years with newly diagnosed intrathoracic tuberculosis. GL and IS were performed in children on 2 consecutive days on ambulatory basis. Samples were examined by Ziehl-Neelsen staining and cultured on an automated BACTEC-MGIT 960 system. Mycobacterial yields (smear and culture) for the 2 sample types (IS and GL) were compared. Four hundred three children (56.6% girls), median age 111 months (interquartile range: 68, 144) were enrolled. Overall yield for acid-fast bacilli and/or Mycobacterium tuberculosis (MTB) by either IS and/or GL was 152 (37.7%). Acid-fast bacilli positivity from IS and GL were 5.7% (23) and 10.4% (42), respectively. Confirmed MTB on culture from IS and GL were 17.9% (72) and 32.5% (127), respectively (P < 0.001). IS and GL identified 17 (4.2%) and 73 (18.1%) additional cases respectively when the other method failed to identify MTB. The combined yields (acid-fast bacilli positivity/MTB) with GL and IS on day 1 (115, 28.5%) were less than that obtained from 2 consecutive GL (135, 33.5%), but better than 2 consecutive IS samples (79, 19.6%; P < 0.001). It is feasible to collect induced sputum and gastric lavage on an ambulatory basis. The yield of MTB obtained by GL is superior to that obtained by IS.


Inhalation injury in burns.
(1) Inhalation injury usually occurs in persons with large flame burns indoors, frequently followed by respiratory failure and death. (2) fiberoptic bronchoscopy accurately verifies the diagnosis. (3) Assessment of pulmonary capillary integrity plus bronchoscopy can predict early respiratory failure. (4) Surfactant deficiency may promote late respiratory failure. (5) Corticosteroids probably are beneficial.


Does Training and Coursework in Domestic Violence Affect Students' Perceptions of Behaviors as Domestic Violence?
Some argue that training and/or coursework in domestic violence (DV) could impact the beliefs criminal justice (CJ) majors have about DV and, in turn, affect their future job performance in cases involving victims of DV. This study examined the association of previous education and training in DV on the beliefs college students hold about what behaviors qualify as DV. Further, it examined the association between CJ versus non-CJ majors on beliefs about DV behaviors. Results indicated prior education on DV, but not training outside of coursework, was associated with differences in students' beliefs about acts of sexual aggression qualifying as DV. Education and training on DV were not significantly related to differences in beliefs about acts of physical or verbal/emotional aggression being DV. Moreover, CJ majors are less likely to believe that verbal/emotional aggression was an act of DV, compared to non-CJ majors. Implications of these findings for policy and educational efforts impacting CJ majors are discussed.


Indian summer heat wave of 2015: a biometeorological analysis using half hourly automatic weather station data with special reference to Andhra Pradesh.
Heat wave is a hazardous weather-related extreme event that affects living beings. The 2015 summer heat wave affected many regions in India and caused the death of 2248 people across the country. An attempt has been made to quantify the intensity and duration of heat wave that resulted in high mortality across the country. Half hourly Physiologically Equivalent Temperature (PET), based on a complete heat budget of human body, was estimated using automatic weather station (AWS) data of four locations in Andhra Pradesh state, where the maximum number of deaths was reported. The heat wave characterization using PET revealed that extreme heat load conditions (PET >41) existed in all the four locations throughout May during 2012-2015, with varying intensity. The intensity and duration of heat waves characterized by "area under the curve" method showed good results for Srikakulam and Undi locations. Variations in PET during each half an hour were estimated. Such studies will help in fixing thresholds for defining heat waves, designing early warning systems, etc.


Fludarabine may overcome resistance to rituximab in IgM-related neuropathy.
Rituximab, a monoclonal antibody directed against CD20, became widely used for the treatment of immunoglobulin M (IgM)-related neuropathy. However, response rate by rituximab monotherapy is no more than 30%. Previous studies revealed that fludarabine acts synergistically with rituximab in vitro and that fludarabine also ameliorates IgM-related neuropathy in a subset of patients. Here we present two cases of IgM-related neuropathy in the background of Waldenström macroglobulinaemia, including one with rituximab resistance. They showed marginal to high titres of both anti-myelin associated glycoprotein and anti-sulphate-3-glucuronyl paragloboside antibodies, and their symptoms were featured by prominent motor deterioration. The combination therapy with rituximab and fludarabine stabilised or improved neuropathic symptoms with tolerable adverse events. Fludarabine may have a potential to overcome rituximab resistance. In conclusion, combination therapy with rituximab and fludarabine should be considered for IgM-related neuropathy, especially when efficacy of rituximab monotherapy is insufficient.


Simultaneous adsorptive removal of three fluoroquinolones using humic acid modified hydrogel beads.
This study elaborates the simultaneous removal of three different fluoroquinolones (FQs), i.e., Norfloxacin (NOR), Lomefloxacin (LOM), and Enrofloxacin (ENR) from water using hydrogel beads of humic acid coated biochar (HA-BC) and chitosan. In our previous study, this adsorbent has already achieved tremendous results for the removal of a single FQ, i.e., ciprofloxacin. Now, initial concentrations of all FQs were set 100 mg/L each, and the maximum adsorbed amounts were 38.08 mg/g (NOR), 25.03 mg/g (LOM), and 29.72 mg/g (ENR). Adsorption attained equilibrium after 24 h, which obeyed the pseudo-second-order kinetic model. The mutation of humic acid-biochar/chitosan hydrogel beads (HBCB) with alcoholic solvents, i.e., methanol and ethanol to replace water decreased its sorption capacities from 38.08 mg/g (NOR) to 34.91 mg/g and 32.19 mg/g, respectively. Similarly, from 25.03 mg/g (LOM) to 22.81 mg/g and 19.91 mg/g, and 29.72 mg/g (ENR) to 26.52 mg/g and 24.64 mg/g. Adsorption isotherm data for all FQs were up to both Langmuir and Freundlich, but it suited more to that of Langmuir adsorption isotherm model. Sorption capacities, for all FQs, had a minor decline due to addition of NaCl, NaNO3, and Na2SO4. However, there was a huge decline when Na3PO4 was added into the adsorption system. Adsorbent was desorbed and regenerated for consecutive removal, and it showed good adsorption in the 4th cycle, i.e., 47 mg/g net adsorption. These results prove that HBCB is not only effective for adsorption removal of ciprofloxacin but also for other FQs too.


Chronic chyluria: a clinical study of 3 patients.
Studies of patients with chyluria or chylothorax have demonstrated significant disruptions of protein, blood and fat metabolism that may result in iron deficiency anemia, hypoproteinemia, hypolipidemia and malnutrition. To document the sequential development of these complications we performed serial clinical and biochemical studies for 2 to 12 years in 3 patients with presumed filarial chyluria whose sole treatment had been diethylcarbamazine. Despite the chronic loss of chyle in the urine these 3 patients did not have significant complications during the period of observation. The weight and blood pressure remained stable. No persistent anemia, hypoproteinemia or hypolipidemia was noted. Except for 1 patient in whom a transient decrease of the creatinine clearance developed during pregnancy, no permanent renal function impairment occurred. These observations suggest that chronic chyluria may not always result in serious alterations of the physical status or body functions of these patients requiring surgical repair, and supports the hypothesis that untreated chyluria could be a relatively benign process in our milieu.


Testosterone administration affects 1H-MRS metabolite spectra in transgender men.
Recently, a variety of studies using different neuroimaging techniques attempted to identify the existence of a brain endophenotype in people with gender dysphoria (GD). However, despite mounting neuroimaging work, brain gender differences and effects of gender-affirming hormone therapy (GAHT) at the metabolite level remain understudied. Thirty-one transgender men (TM) before and after testosterone administration (7.7 months ± 3.5 months), relative to 30 cisgender men (CM) and 35 cisgender women (CW) underwent magnetic resonance spectroscopy (1H-MRS) at two time points. Two brain regions were assessed, i.e. the lateral parietal cortex and the amygdala/anterior hippocampus. Associated metabolites that were measured include N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), glutamate and glutamine (Glx), myo-inositol (mI), glycine (Gly) and their respective ratios. A critical time by group interaction revealed an effect of GAHT in the lateral parietal cortex of TM. MI+Gly/Cr ratios decreased upon initiation of GAHT. In addition, NAA/Cr and Cho/Cr ratios were lower in CW when compared to CM in the lateral parietal cortex. Glx levels and Glx/Cr ratios in TM differed from those in CW in the amygdala/anterior hippocampus. Interestingly, pubertal age of onset of gender dysphoria (i.e. GD) in TM differentially affected testosterone-mediated effects on Cr concentration and NAA/Cr ratios when compared to childhood and adult GD onset in the amygdala/anterior hippocampus. This 1H-MRS study demonstrated that testosterone administration shifts mI+Gly/Cr ratios in the parietal cortex. In the amygdala/anterior hippocampus, modulation of metabolite concentrations by age of onset of GD is suggestive for a possible developmental trend.


Kisspeptin has an independent and direct effect on the pituitary gland in the mare.
To more clearly understand the equine gonadotrope response to kisspeptin and gonadotropin releasing hormone (GnRH), peripheral LH and FSH were quantified in diestrous mares after treatment with either equine kisspeptide (eKp-10, 0.5 mg iv), GnRH (25 μg iv), or a combination thereof every 4 h for 3 days. The following observations were made: 1) a diminished LH and FSH response to eKp-10 and GnRH was observed by Day 3, but was not different by treatment, 2) a decrease in basal LH concentration was observed from Day 1 to Day 3 for the eKp-10, but not the GnRH treated mares, 3) there was no change in basal FSH with either treatment. Additionally, pre-treatment with GnRH antagonist (antide 1.0 mg iv) eliminated any measurable change in LH after eKp-10 (1.0 mg iv) treatment. Both GnRH and kisspeptin are Gαq/11 coupled receptors, therefore quantifying the rise in intracellular calcium following treatment with cognate ligand allows simultaneous assessment of receptor activation. Direct stimulation of equine primary pituitary cells with GnRH and/or eKp-10 demonstrates three distinct populations of pituitary cells: one population responded to both eKp-10 and GnRH, a second, independent population, responded to only eKp-10, and a third population responded only to GnRH. These populations were confirmed using co-immunofluorescence of hemipituitaries from mares in diestrus. Although the rise in peripheral LH concentration elicited by eKp-10 is dependent on GnRH, this work suggests that kisspeptin also has a specific and direct effect on the equine gonadotrope, independent of GnRH.


[Bone and metabolism].
Bone is now considered as a particular endocrine organ. Its endocrine function is not yet fully understood and has been the subject of several conferences at the European Society of Endocrinology Congress 2018. Bone regulates phosphate metabolism by secreting fibroblast growth factor 23; it also regulates glucose metabolism via osteocalcin and energy metabolism, thanks to lipocalin 2, a new hormone acting on the brain. In addition, the incidence of diabetes continues to grow, and its impact on bone has been demonstrated, with an increased risk of fractures regardless the type of diabetes. The mechanism of bone fragility in this disease is not fully known but it involves a decrease in bone turnover and bone demineralization. Recent findings on the role of bone on glucose and mineral metabolism could open therapeutic perspectives, especially for the treatment of diabetes or obesity.


Catechol-O-methyltransferase Val158Met polymorphism and risk of autism spectrum disorders.
Autism spectrum disorders (ASD) are a family of childhood-onset neurodevelopmental disorders with complex genetic mechanisms underlying their aetiology. The aim of this case-control study was to evaluate the effect of the catechol-O-methyltransferase (COMT) gene Val158Met polymorphism on ASD risk in a Chinese Han population. The COMT gene Val158Met polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in children (≤ 18 years old) with ASD and healthy control subjects. The frequency of the Val158/Val158 genotype in children with ASD (22/186; 11.8%) was significantly lower than in controls (38/186; 20.4%). When stratifying by select-item scores on the Autism Diagnostic Interview-Revised protocol, it was found that children with 'current overactivity' and 'ever overactivity' had a significantly lower frequency of the Val158/Val158 genotype than those without. There were no significant associations between the COMT gene Val158Met polymorphism and ASD subtypes. The COMT gene Val158Met polymorphism may be a biomarker for phenotypic variation in ASD, but these preliminary findings remain tentative, pending replication in larger, independent samples.


Stroke and acute myocardial infarction in the thrombolytic era: clinical correlates and long-term prognosis.
Thirteen (1.8%) of 708 patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I, II and III trials developed a stroke. Four strokes were hemorrhagic and nine were nonhemorrhagic. Of five prespecified risk factors for intracranial hemorrhage (age greater than 65 years, history of hypertension, history of prior cerebrovascular disease, aspirin use and acute hypertension), two patients had two risk factors and one patient had one risk factor. However, 80% of patients without intracranial hemorrhage had at least one risk factor and 31% had two risk factors. No patient with a prior stroke or transient ischemic attack (all greater than 6 months previously) had an intracranial hemorrhage. Of three prespecified risk factors for nonhemorrhagic stroke (atrial fibrillation, prior cerebrovascular disease and large anterior wall infarction), only the occurrence of a large anterior myocardial infarction (with ejection fraction less than 45%) was a predictor (p = 0.0015). The in-hospital death rate was 25% for patients with hemorrhagic stroke versus 11% for patients with a non-hemorrhagic stroke and 6% for those patients without a stroke. Furthermore, the hospital stay was greater than 50% longer in patients who had a stroke than in those who did not. Thus, intracranial hemorrhage remains an unpredictable risk in patients treated with thrombolytic therapy and cerebral infarction is related to anterior myocardial infarction and poor left ventricular function. Both types of stroke are associated with substantial morbidity and mortality.


Assessment of splanchnic perfusion by gastric tonometry in patients with acute hypovolemic burn shock.
To compare the changes in pHi and intramucosal-arterial CO(2)-gap with invasive haemodynamic and global perfusion measurements during hypovolemic burn shock and to evaluate the sensitivity of these parameters as an early predictor of mortality in patients with extensive burns. Prospective, controlled, clinical study. An eight-bed intensive burn care unit in a university-affiliated hospital. Fifty severely burned patients with TBSA burned >25% BSA. During the first 48h after burn, gastric intramucosal CO(2) was measured every 8h using automated air tonometry. pHi and intramucosal-arterial CO(2)-gap were calculated. Simultaneously invasive haemodynamic data were registered by the transpulmonary thermodilution technique, using the mean of triplicate injections. The intramucosal-arterial CO(2)-gradient and pHi were compared with haemodynamic and global perfusion data by regression analysis. Mean pHi and CO(2)-gap values at 8 and 24h after injury were compared between survivors and non-survivors to evaluate the prognostic significance of this parameter. Regression analyses revealed no or a negligible correlation between intramucosal and haemodynamic or perfusion data, even during the critical low flow-high resistance phase of resuscitation. Mean pHi and PCO(2)-gap at 8 and 24h did not differ significantly between survivors and non-survivors. Gastric tonometry is a poor indicator of splanchnic perfusion in patients with burn shock, even when all precautions are taken to prevent methodological errors. The intramucosal-arterial PCO(2)-gap and pHi do not distinguish survivors from non-survivors. Therefore, gastric tonometry does not seem to improve the ability to anticipate and avert regional anaerobic metabolism during burn shock and its routine use in these patients cannot be recommended.


Exposing Anopheles mosquitoes to antimalarials blocks Plasmodium parasite transmission.
Bites of Anopheles mosquitoes transmit Plasmodium falciparum parasites that cause malaria, which kills hundreds of thousands of people every year. Since the turn of this century, efforts to prevent the transmission of these parasites via the mass distribution of insecticide-treated bed nets have been extremely successful, and have led to an unprecedented reduction in deaths from malaria1. However, resistance to insecticides has become widespread in Anopheles populations2-4, which has led to the threat of a global resurgence of malaria and makes the generation of effective tools for controlling this disease an urgent public health priority. Here we show that the development of P. falciparum can be rapidly and completely blocked when female Anopheles gambiae mosquitoes take up low concentrations of specific antimalarials from treated surfaces-conditions that simulate contact with a bed net. Mosquito exposure to atovaquone before, or shortly after, P. falciparum infection causes full parasite arrest in the midgut, and prevents transmission of infection. Similar transmission-blocking effects are achieved using other cytochrome b inhibitors, which demonstrates that parasite mitochondrial function is a suitable target for killing parasites. Incorporating these effects into a model of malaria transmission dynamics predicts that impregnating mosquito nets with Plasmodium inhibitors would substantially mitigate the global health effects of insecticide resistance. This study identifies a powerful strategy for blocking Plasmodium transmission by female Anopheles mosquitoes, which has promising implications for efforts to eradicate malaria.


On phenotyping with isoniazid: the use of urinary acetylation ratio and the uniqueness of antimodes. Study of two Amerindian populations.
Various conventions have been used to express the activity of polymorphic hepatic N-acetyltransferase of isoniazid. Among them, two of the most common are the "percentage of acetylisoniazid" and the "inactivation index." A third alternative convention is proposed, the "molar acetylation ratio," which showed the most clear-cut bimodal distribution when applied to the results obtained for Cuna and Teribe Amerindians living in Panama. Through this method a unique antimode was assigned to each Amerindian group and the same frequency of slow acetylators (24% to 29%) was found, unlike the results obtained by conventional approaches and antimodes derived from white populations.


Coexisiting type 1 diabetes and celiac disease is associated with lower Hba1c when compared to type 1 diabetes alone: data from the Australasian Diabetes Data Network (ADDN) registry.
To compare HbA1c and clinical outcomes in adolescents and young adults with type 1 diabetes (T1D), with or without celiac disease (CD). Longitudinal data were extracted from ADDN, a prospective clinical diabetes registry. Inclusion criteria were T1D (with or without CD), ≥ 1 HbA1c measurement, age 16-25 years and diabetes duration ≥ 1 year at last measurement. Multivariable Generalised Estimated Equation models were used for longitudinal analysis of variables associated with HbA1c. Across all measurements, those with coexisting T1D and CD had lower HbA1c when compared to those with T1D alone (8.5 ± 1.5% (69.4 ± 16.8 mmol/mol) vs. 8.7 ± 1.8% (71.4 ± 19.8 mmol/mol); p < 0.001); lower HbA1c was associated with shorter diabetes duration (B = - 0.06; 95% CI - 0.07 to - 0.05; p < 0.001), male sex (B = - 0.24; - 0.36 to - 0.11; p < 0.001), insulin pump therapy use (B = - 0.46; - 0.58 to - 0.34; p < 0.001), coexistence of T1D and CD (B = - 0.28; - 0.48 to - 0.07; p = 0.01), blood pressure (B = - 0.16; - 0.23 to - 0.09; p < 0.001) and body mass index (B = -- 0.03; - 0.02 to - 0.04; p = 0.01) in the normal range. At last measurement, 11.7% of the total population had a HbA1c < 7.0% (53.0 mmol/mol). Across all measurements, coexisting T1D and CD is associated with lower HbA1c when compared to T1D alone. However, HbA1c is above target in both groups.


Human mesenchymal stem cells successfully improve skin-substitute wound healing.
Large or deteriorated skin defects are sometimes life threatening. There is increasing evidence that adult stem cells are useful for tissue regeneration. Human mesenchymal stem cells (hMSCs) are self-renewing and are potent in differentiating into multiple cells and tissues. To investigate the effects of hMSCs in cutaneous wound healing. Wound healing was studied in an hMSC-populated porcine skin substitute, using a nude rat model to minimize immune reactions. Full-thickness skin and soft tissue defects of 1.5 x 1.5 cm in size, including the panniculus carnosus, were excised and covered with hMSCs and basic fibroblast growth factor (bFGF)-soaked skin substitutes and an evaluation was made of wound size, histology and protein expression at 3, 7 and 42 days after injury. The wound size was significantly smaller in the hMSC-treated groups (P < 0.01) and any dose of bFGF (1, 10, 100 microg) enhanced the healing (P < 0.01). The re-epithelialization markers integrin alpha3 and skin-derived antileucoproteinase were remarkably increased with the presence of bFGF in a dose-dependent manner, while the mesenchymal cell surface markers CD29 and CD44 were downregulated in a time-dependent manner. Human pancytokeratin, which does not cross-react with rat antigens, was observed by Western blotting at 38 kDa and 42 kDa from the hMSC-treated tissues on day 7. The expression levels were elevated by 10 microg bFGF (P < 0.01). The immunohistochemical expression of human pancytokeratin was only observed in the hMSC-treated groups. These data suggest that hMSCs together with bFGF in a skin defect model accelerate cutaneous wound healing as the hMSCs transdifferentiate into the epithelium.


The role of the ninth and tenth type III domains of human fibronectin in cell adhesion.
Fibronectins (FN) contain sites, in addition to the cell recognition site RGD in the tenth type III domain (FIII10), that are required for adhesive activity. The role of FIII10 and the adjacent FIII9 was analysed in functional cell adhesion assays recombinant FIII domains in which the domain boundaries were strictly conserved. FIII9 had no adhesive activity. FIII10, and FIII9 plus FIII10 had less activity than FN, whereas the activity of FIII9-10 was similar to FN. We conclude that FIII9 acts synergistically with FIII10 in cell adhesion, and that this synergy is dependent upon the structural integrity of the FIII9-10 pair of domains.


Febrile infection-related epilepsy syndrome (FIRES): does duration of anesthesia affect outcome?
We conducted a retrospective multicenter study on children who had been included in eight studies published between November 2001 and July 2010 to explore the correlations between burst-suppression coma (BSC) with outcome in febrile infection-related epilepsy syndrome (FIRES). The 77 enrolled patients presented with prolonged refractory status epilepticus. BSC was induced in 46 patients. Cognitive levels at follow-up were significantly associated with duration of a BSC (p=0.005). The outcome of FIRES is poor. Treatment by inducing a prolonged BSC was associated with a worse cognitive outcome.


Immune-mediated pathogenesis of Borna disease.
Borna disease is an endemic progressive encephalomyelitis of horses and sheep prevalent in central Europe. A wide variety of animal species, ranging from chickens to primates can be infected experimentally with the causative virus, which is only poorly characterized. Furthermore, BD virus-specific antibodies have been detected in sera and cerebrospinal fluids of psychiatric patients. Our studies on the pathogenesis of BD have shown that-at least in rats-the disease is not caused by the infecting virus itself, but by a virus-induced immunopathological reaction. Thus, after intracerebral infection immunoincompetent rats do not get the disease despite persistent virus replication in cells of the central nervous system. However, after adoptive transfer of immune cells from diseased rats, immunoincompetent rats exhibit full-blown BD. Recently, we have been successful in establishing a virus-specific T cell line of the helper/inducer phenotype (CD4+). This T cell was shown to play an important role in the pathogenesis of BD, suggesting that the disease is caused by a delayed type hypersensitivity reaction.


The value of serum Sema4D level in predicting the prognosis of patients with acute ST-segment elevation myocardial infarction and with high thrombus burden.
Acute ST-segment elevation myocardial infarction (STEMI) is a serious cardiovascular disease. High thrombus burden is an independent risk factor for poor prognosis of acute myocardial infarction. However, there is no study on the correlation between soluble semaphorin 4D (sSema4D) level and high thrombus burden in patients with STEMI. This study aimed to investigate the relationship between sSema4D level and the thrombus burden of STEMI and further explore its effect on the main predictive value of the occurrence of major adverse cardiovascular events (MACE). From October 2020 to June 2021, 100 patients with STEMI diagnosed in our hospital's cardiology department were selected. According to the thrombolysis in myocardial infarction(TIMI)score, STEMI patients were divided into high thrombus burden groups (55 cases) and non-high thrombus burden groups (45 cases) 0.74 patients with stable coronary heart disease (CHD) were selected as stable CHD group, and 75 patients with negative coronary angiography (CAG) were selected as control group. Serum sSema4D levels were measured in 4 groups. The correlation between serum sSema4D and high-sensitivity C-reactive protein (hs-CRP) in patients with STEMI was analyzed. The relationship of serum sSema4D levels between the high and non-high thrombus burden group was evaluated. The effect of sSema4D levels on the occurrence of MACE was explored in one year after percutaneous coronary intervention. Serum sSema4D level was positively correlated with hs-CRP level in STEMI patients (P < 0.05) with a correlation coefficient of 0.493. The sSema4D level was significantly higher in the high versus non-high thrombus burden group (22.54(20.82,24.17), P < 0.05). Moreover, MACE occurred in 19 cases in high thrombus burden group and 3 cases in non-high thrombus burden group. The results of Cox regression analysis showed that sSema4D was an independent predictor of MACE (OR = 1.497,95% CI: 1.213-1.847, P < 0.001). The sSema4D level is associated with coronary thrombus burden and is an independent risk factor for MACE.


The relationship of fatty acid composition and surface activity of lung extracts.
Male weanling rats were fed fat-free diets supplemented with 4% (w/w) safflower oil (control) or 4% tripalmitin (essential fatty acid (EFA) deficient) for 14 weeks. Whereas the amount of lecithin in lung lavage material remained unchanged, lung lavage lecithin from EFA-deficient rats contained significantly less palmitic acid (61.4 +/- 2.0% vs. 77.4 +/- 5.8%, P less than 0.01) than that from controls. Surface tension vs. area hysteresis loops were obtained for total lipid extracts (TLE) of lung lavage fluid, intra- and extra-cellular lipoprotein fractions (IBI and IBE) and lipid extracts of those lipoprotein fractions (LBI and LBE). A significant increase in minimal surface tension (gammamin) was found for all samples obtained from EFA-deficient rats as compared to controls. Refeeding of diets containing safflower oil for 7-14 days reversed these changes. Air pressure-volume curves on degassed, excised lungs indicated that greater pressure is required to maintain a given lung volume in EFA-deficient rats. These results support the hypothesis that the fatty acid composition of pulmonary surfactant lecithins is a major determinant of the surface activity of lung extracts.


Two-Color Imaging of Nonrepetitive Endogenous Loci in Human Cells.
Tools for live cell imaging of multiple nonrepetitive genomic loci in mammalian cells are necessary to study chromatin dynamics. Here, we report a new system based on two chromosomally integrated orthogonal irregular repeat arrays and particularly a new general strategy to construct irregular repeat arrays. Briefly, we utilized a "bridge oligonucleotide-mediated ligation" protocol to assemble 8-mer repeats de novo which were then combined into a final 96-mer repeat array using Golden Gate cloning. This strategy was used for assembling a new mutant TetO irregular repeat array, which worked orthogonally to the wild type TetO repeat. Single copy integration of the new repeat array did not cause replication deficiencies at the tagged locus. Moreover, the mutant TetO irregular repeat could also be visualized by CRISPR imaging. Our new irregular repeat assembly method demonstrates a generally applicable strategy that can be used for assembling additional orthogonal repeat arrays for imaging genomic loci and irregular repeats to visualize RNA or proteins via signal amplification.


One-Year Medication Adherence and Persistence in Rheumatoid Arthritis in Clinical Practice: A Retrospective Analysis of Upadacitinib, Adalimumab, Baricitinib, and Tofacitinib.
This study evaluated 12 months adherence and persistence among Janus kinase inhibitors (upadacitinib, baricitinib, tofacitinib) and adalimumab, a tumor necrosis factor inhibitor (TNFi), in patients with rheumatoid arthritis (RA). This retrospective analysis used administrative claims data from the Merative™ MarketScan® Research Databases (2018-2022). Eligible adults had ≥ 1 RA diagnosis before the index date, ≥ 1 pharmacy claim for index medication, and ≥ 12 months of continuous insurance enrollment pre- and post-index. Adherence to treatment [defined as proportion of days covered (PDC) ≥ 80%], risk of treatment discontinuation, and mean time to discontinuation were assessed during the 12 months follow-up. Adjusted odds ratios (aOR), adjusted hazard ratios (aHR), and 95% confidence intervals (CI) were reported. In total, 6317 patients were included (683 upadacitinib, 3732 adalimumab, 132 baricitinib, 1770 tofacitinib). Compared with upadacitinib, patients initiating adalimumab [aOR (95% CI): 0.82 (0.69, 0.96)], baricitinib [0.46 (0.31, 0.68)], and tofacitinib [0.74 (0.62, 0.88)] were significantly less likely to achieve PDC ≥ 80%. Risk of treatment discontinuation was significantly higher in patients treated with adalimumab [aHR (95% CI): 1.14 (1.01, 1.29)], baricitinib [1.48 (1.16, 1.90)], and tofacitinib [1.22 (1.07, 1.38)] compared with upadacitinib. Mean time to discontinuation was 256 (upadacitinib), 249 (adalimumab), 221 (baricitinib), and 239 (tofacitinib) days. Similar results were observed in patients with prior TNFi use. Patients with RA, regardless of recent TNFi experience, initiating upadacitinib were significantly more likely to be adherent and less likely to discontinue therapy compared to adalimumab, baricitinib, and tofacitinib in the first 12 months of treatment.


A Rare Cause of Acute Dyspnoea: Reinke Oedema.
Reinke oedema is a benign condition due to fluid collection within subepithelial space of the true vocal fold. This phenomenon is predisposed by chronic smoking, alcohol consumption and contribution of laryngopharyngeal reflux. Although benign, it may be life threatening when bilateral vocal folds are affected causing airway obstruction. In this report, awake tracheostomy was performed for a 65- year- old lady with stridor secondary to severe Reinke oedema. The importance of establishing a definitive airway is highlighted here in securing a difficult airway. The online version contains supplementary material available at 10.1007/s12070-023-03714-4.


Environmental constrains on post-partum ovarian activity in Tanzanian Zebu cows.
Milk progesterone measurements were used to study post-partum ovarian activity and risk factors for ovarian dysfunction in Zebu cows reared under a traditional pastoral management system in three villages in Morogoro region, Tanzania. Milk samples for progesterone analysis were collected twice per week from a total of 98 lactations. The most prevalent ovarian dysfunction detected was delayed onset of post-partum ovarian activity and cessation of cyclical ovarian activity after a period of normal ovarian function. Prolonged luteal phases were not observed. Resumption of post-partum ovarian activity was observed in 61 (62.2%) cows. Pregnancy was diagnosed in 43 (43.8%) out of 98 cows and was terminated by abortion in 7 (16.3%) cows. The median number of days from calving to resumption of ovarian activity was lower in cows that calved during the dry season (167 days) as compared with those that calved in the rainy season (200 days, P=0.03), probably because ovarian function was stimulated in cows entering the rainy season first after the puerperal phase had ended. Cyclical ovarian activity ceased in seven (11.5%) cows, and all but one case of cessation of ovarian activity took place during the dry season. Cows in their first and second parities experienced prolonged intervals (244 days) between calving and onset of ovarian activity compared with cows in their third or later parity (172 days, P=0.03). Cows with marked losses in body condition experienced prolonged intervals between calving and onset of ovarian activity (229 days) as compared with cows that lost <1 body condition unit (172 days, P=0.03). The time interval from calving to resumption of ovarian activity varied between the three villages of the study (142, 192 and 229 days, P=0.05), indicating local differences in management practices.


Differences between Metabolically Healthy vs Unhealthy Obese Children and Adolescents.
Obesity is on the rise worldwide. An obesity subtype, metabolically healthy obese (MHO), is resilient to unfavorable metabolic and cardiovascular effects. Factors predicting MHO phenotype are not well characterized. We aimed to identify MHO and metabolically unhealthy obese (MUO) children and adolescents with respect to metabolic factors, and to find predictors of MHO subtype. A retrospective chart review was done on children, ages 4-19 years, 99% African-American/Caribbean, with BMI ≥95th %tile. MUO was defined as meeting ≥1 of the following: fasting glucose ≥100 mg/dl, HbA1c >5.6%, BP ≥90th %tile, TG ≥150 mg/dl, or HDL <40 mg/dl. Study included 189 subjects, 37.6% were MHO and 62.4% MUO. MHO subjects were younger (mean ± SD, 11.6 ± 3.3 vs 12.9 ± 3.2 years; p < 0.009) and had lower BMI %tile (98.4 ± 1.4 vs 98.8 ± 2.1; p < 0.04), smaller waist (94.2 ± 15.2 vs 101.4 ± 17 cm; p < 0.003) and hip circumferences (105.3 ± 15.6 vs 113.5 ± 15.4 cm; p < 0.001), lower fasting insulin (18.5 ± 10.2 vs 24.2 ± 14.3 μU/ml; p < 0.022), and lower HOMA-IR (4.1 ± 2.4 vs 5.5 ± 3.6; p < 0.022). Acanthosis nigricans was noted less frequently in MHO than MUO (p < 0.005). In stepwise logistic regression, age and BMI %tile were significant predictors of MHO. We found that 38% of obese children are MHO. They are younger and have lower BMI %tiles. Lifestyle modification initiated at an early age may prevent metabolic abnormalities.


Expression of super cervical ganglion-10 (SCG-10) mRNA in the monkey cerebral cortex during postnatal development.
We used Northern blot analysis to measure SCG10 mRNA expression in various areas of the monkey cerebral cortex during postnatal development. In all areas, SCG10 mRNA expression was highest immediately after birth, decreased sharply until postnatal day 70 (P70) and then decreased slowly until the adult stage. Expression levels were similar in all areas at all time points during development, including the adult stage. These findings confirm that axonal growth in the monkey cerebral cortex is most vigorous before or during the perinatal period, progresses similarly in all areas until P70, and continues at lower levels during late development.


Pubovaginal sling using Duraderm graft: intermediate follow-up and patient satisfaction.
To assess outcome and patient satisfaction utilizing Duraderm allograft as sling material. Twenty five patients undergoing the Duraderm sling procedure were evaluated by pelvic examination, post-void residual urine, and multi-channel urodynamics. Follow-up included repeat examination, stress test, and chart review. Patient satisfaction was assessed by phone interview with an independent examiner. Outcome was defined as dry (no leaking at all and patient perception of satisfaction), improved (minimal leak requiring < or =1 pad daily and patient perception of satisfaction), or failure. Average age was 62.0 years (30-83); average daily preoperative pad usage was 3.5 (2-8). Duraderm allograft measuring 2 x 12 cm was used. Mean postoperative catheter time was 7.7 days (3-37 days). At 6 months, 17/25 (68%) were dry, 6 (24%) improved, and 2 (8%) failed. Mean intermediate follow-up at 14.8 months (8-23 months) revealed 8/25 (32%) patients were dry, 9 (36%) were improved, and 8 (32%) failed Duraderm sling. Mean pad use after surgery was 1.4 (0-6). Of the 25, 19 (76%) were satisfied with the surgical outcome, 17 (68%) noted they would have surgery again, and 17 (68%) would recommend the procedure. Initial results of pubovaginal sling using Duraderm graft are satisfactory; however, longer term follow-up is disappointing. Graft degeneration previously described after utilization of cadaveric fascia lata may be possible following implantation of cadaveric dermis.


Clinicians' perspectives on the integration of electronic patient-reported outcomes into dermatology clinics: a qualitative study.
Skin conditions can have profound negative symptomatic and psychological effects. Failure to address these effects can lead to poor treatment adherence and/or patient dissatisfaction. Despite patient-reported outcome (PRO) use being highly recommended, real-world adoption has been slow. To assess clinicians' perceived facilitators and barriers to using PROs in daily practice. We conducted in-person semi-structured interviews with 19 clinicians and thematic analysis of transcripts. Three main themes emerged: (1) clinicians' attitudes about the value of Skindex-16 in daily practice, (2) patient attitudes influencing clinicians' use of Skindex-16, and (3) clinicians' perceptions of their ability to use PROs successfully for clinical care. Clinicians recognized benefits to using Skindex-16, such as revealing patients' hidden concerns and highlighting discrepancies with the clinician's severity assessments. Conversely, clinicians also identified limitations, such as time constraints and lack of relevance for some skin conditions. Patient complaints about PRO relevance have influenced clinicians' use of Skindex-16 negatively. Finally, some clinicians recognized the need for more training in score interpretation and implementation strategies for optimal clinical flow. While most clinicians believed PROs like Skindex-16 can be useful for patient care, barriers need to be addressed to make PROs more practical for routine clinical care.


Corrigendum to "Solid Pseudopapillary Neoplasm of the Pancreas with High-Grade Malignant Transformation Involving p16-RB Pathway Alterations".
[This corrects the article DOI: 10.1155/2020/5980382.].