Early fixation strategies for high energy pelvic ring injuries - the Zurich algorithm.
In isolated high energy pelvic ring injuries, early surgical and nonsurgical fixation belongs to the rescue tools required for rapid recovery. With the increasing use of pelvic binders on scene, these patients frequently arrive in a better condition at the level I trauma centre than without any measures of immobilisation. We describe our surgical tools to achieve rapid fixation within the first hours after arrival, taking into account if additional injuries or special stations are relevant.


[Features of episodes of mental disorders in chronic renal insufficiency (clinico-morphologic study)].
The authors studied the traits of psychotic attacks in 40 patients with terminal stages of chronic renal insufficiency. They were expressed in atypical delirious, delirio-amentive and amentive conditions. 8 cases were studied morphologically. The pathological process in the brain was characterized as toxico-dyshomeostatic encephalopathy. The pathogenesis of such disorders is discussed.


Endothelial ErbB4 deficit induces alterations in exploratory behavior and brain energy metabolism in mice.
The receptor tyrosine kinase ErbB4 is present throughout the primate brain and has a distinct functional profile. In this study, we investigate the potential role of endothelial ErbB4 receptor signaling in the brain. Here, we show that the endothelial cell-specific deletion of ErbB4 induces decreased exploratory behavior in adult mice. However, the water maze task for spatial memory and the memory reconsolidation test reveal no changes; additionally, we observe no impairment in CaMKII phosphorylation in Cdh5Cre;ErbB4f/f mice, which indicates that the endothelial ErbB4 deficit leads to decreased exploratory activity rather than direct memory deficits. Furthermore, decreased brain metabolism, which was measured using micro-positron emission tomography, is observed in the Cdh5Cre;ErbB4f/f mice. Consistently, the immunoblot data demonstrate the downregulation of brain Glut1, phospho-ULK1 (Ser555), and TIGAR in the endothelial ErbB4 conditional knockout mice. Collectively, our findings suggest that endothelial ErbB4 plays a critical role in regulating brain function, at least in part, through maintaining normal brain energy homeostasis. Targeting ErbB4 or the modulation of endothelial ErbB4 signaling may represent a rational pharmacological approach to treat neurological disorders.


Use of endoscopic biopsies and microelectrodes to study human gastric acid secretion in vitro.
We have investigated the possibility of measuring acid secretion from human gastric mucosa in vitro as a potential pharmacological preparation. We used open-ended 10 microns-tip, lix-based glass microelectrodes to measure the pH of the mucus layer of gastric biopsies superfused with a HEPES buffered solution in an organ bath. With no drugs added the pH of the mucus layer of biopsies from the body of the stomach stayed constant but the pH of antral biopsies fell slightly by a median of 0.12 pH units over 80 min (P < 0.05). Stimulation of the biopsies with 1-100 microM histamine produced a dose-dependent decrease in pH which was significantly greater in biopsies from the gastric body than from the antrum. 500 pM pentagastrin produced a median fall in pH of 1.20 (P < 0.01) which was prevented by the prior addition of 100 microM omeprazole or 10 microM ranitidine. Omeprazole or ranitidine alone produced slight rises in the median pH of 0.47 (P < 0.05) and 0.26 (P < 0.05) units respectively. Those biopsies which were infected with Helicobacter pylori had a slightly elevated initial pH of about 0.2 of a pH unit (P < 0.05). This novel system provides a means to study human gastric acid secretion in vitro and may be valuable in the testing of new drugs on the stomach.


Incidence of X-Y aneuploidy in sperm of two indigenous cattle breeds by using dual color fluorescent in situ hybridization (FISH).
The present study reports on the incidence of X-Y aneuploidy in the sperm population of two indigenous cattle breeds reared in Italy for beef purposes, the Podolian and Maremmana. Totally, more than 50 000 sperm nuclei from 10 subjects (5 from each breed) have been fluorescent in situ hybridization (FISH) analyzed by using Xcen- and Y-chromosome-specific painting probes. In both breeds, the fraction of Y-bearing sperm was significantly higher (P < 0.01) compared with the X-counterpart. The rates of X-Y aneuploidy were 0.180% and 0.200%, respectively, in the Podolian and Maremmana. No significant interindividual differences were found. Average frequencies of disomic and diploid sperm were 0.149% and 0.031% in the former and 0.098% and 0.102% in the latter. Significant differences (P < 0.05) were found among the XX-XY and YY-disomy classes in both breeds, while diploidy classes were uniformly represented. In the Podolian breed, disomies were more frequent than diploidies (P < 0.05), whereas in the Maremmana they showed similar frequencies. In both breeds disomies arising from errors in meiosis I (X-Y disomies) were more represented than those arising in meiosis II (XX and YY), while this difference was not detected for diploidies. The present study provides specific information on the incidence of X-Y sperm aneuploidy in two indigenous breeds of cattle, in order to establish a breed-specific 'aneuploidy data-base' that could be used as reference for genetic improvement and future monitoring of the reproductive health of the breed.


Jab1 expression is associated with TGF-β1 signaling in chronic rhinosinusitis and nasal polyposis.
Jab1, which is a fifth component of COP9 signalosome, plays an essential role in cell growth and proliferation. Jab1 is also shown to regulate transforming growth factor-beta (TGF-β) signaling in carcinoma cells. The aim of the present study was to investigate the expression and the correlation of Jab1 and TGF-β1 in chronic rhinosinusitis and nasal polyposis. Here, we show the elevated expression of Jab1 and TGF-β1 in diseased mucosa without nasal polyps and a correlation between Jab1 and TGF-β1 expression. Forty-six samples (26 patients with nasal polyps, 10 patients with chronic rhinosinusitis and 10 control subjects) were included to this study. Immunohistochemistry and Western blotting were performed for the assessment of Jab1 and TGF-β1 localization and the expression of proteins. Double staining of both proteins showed that Jab1 and TGF-β1 were colocalized in the epithelium, inflammatory cells and the vascular endothelium of nasal mucosa. There was a significant increase in the expression of TGF-β1 and Jab1 in patients without nasal polyps and a significant decrease in patients with nasal polyps compared to controls. Moreover, correlation was detected between the expression of Jab1 and TGF-β1 in chronic rhinosinusitis and nasal polyposis. Our results demonstrate that chronic rhinosinusitis is characterized by elevated expression of Jab1 and TGF-β1 compared to nasal polyposis and Jab1 may play a vital role in the pathogenesis of both chronic rhinosinusitis and nasal polyposis.


Gulliver meets Descartes: early modern concepts of age-related memory loss.
Age-related memory loss was a marginal issue in medical discussions during early modern times and until well into the second half of the 17th century. There are many possible explanations: the lack of similar traditions in antiquity and in the Middle Ages, insufficient physiological and morphological knowledge of the brain, and the underlying conflict between idealistic and materialistic perspectives on the functions of the soul and the conditions of these in old age. After these boundaries had been pushed back by the influence of Cartesianism and Iatromechanism, the problem of age-related memory loss was increasingly regarded as a physical illness and began to receive more attention. This trend first occurred in medicine, before spreading to the literary world, where the novel "Gulliver's Travels" is one clear and famous example.


A randomized open label parallel group pilot study to evaluate efficacy of Ayurveda interventions in the management of asymptomatic and mild COVID-19 patients-experiences of a Lucknow based level 2 hospital of Uttar Pradesh, India.
SARS--CoV-2 has emerged as a global threat since its onset in December 2019. India has also been severely affected by the dreadful Corona Virus and is currently battling one of the worst pandemics of history. WHO and the world medical fraternity are putting their efforts to materialize a treatment or vaccine for this novel virus. A randomized open label parallel group study was designed in a Lucknow based level 2 COVID hospital to evaluate the efficacy of Ayurvedic interventions in the management of asymptomatic and mild COVID 19 patients. To evaluate the efficacy of Ayurveda in the management of mildly affected COVID-19 patients. The current trial was an open label randomized 10-day study. Total 120 asymptomatic and/or mild COVID-19 positive patients fulfilling inclusion criteria were randomly grouped into three. RT-PCR of all the patients were done on 5th, 7th and on 10th day respectively. The observations were noted and results were analyzed statistically. Kruskal-Wallis test and Wilcoxon Sign rank test were used for data analysis where applicable. Improvement in symptoms, enhancement in Agni and recovery from COVID infection was observed. The results obtained were encouraging and showed better viral clearance and control of symptom progression in the patients placed on Ayurvedic medications. The promising results in the study showed that an approach involving Ayurveda can be helpful for the management of the mild COVID-19 patients. Ayurveda can be used to limit community spread and check disease progression to a more appalling state. Trial was registered with Clinical Trials Registry- India (CTRI registration number: CTRI/2020/06/025800.


Elevated peripheral airway nitric oxide in bronchiectasis reflects disease severity.
Bronchiectasis is characterised by neutrophilic bronchial inflammation and patients are prone to recurrent or chronic bacterial airway infections. Direct measurement of lung inflammation would be useful in order to assess disease activity and guide need for antibiotic treatment and to monitor response. Current methods of monitoring inflammation are invasive, indirect or insensitive. Exhaled nitric oxide (FE(NO)) is a direct simple non-invasive test of inflammation used in other airway diseases. The aim of this study was to test whether peripheral airway nitric oxide (C(alv)) can provide a clinically useful direct measure of inflammation in the lungs of patients with bronchiectasis. Fifty three patients with bronchiectasis were studied when clinically stable and a further 20 patients during an exacerbation of bronchiectasis. FE(NO) was measured by chemiluminescence using a NO analyser. Two models of pulmonary exchange dynamics were used to calculate proximal and peripheral contributions to final FE(NO) concentration. FE(NO) was elevated in bronchiectasis patients compared to 30 healthy controls (p < 0.05). Compartmental modelling reveals that this elevation is due to an increase in peripheral airway NO (bronchiectasis 3.6 ppb (2.1), controls 2.7 ppb (1.5) p < 0.05) whereas proximal airway NO levels are normal (bronchiectasis 777(751) pl/s, controls 582(579) pl/s ns). C(alv) relates to disease severity measured by lung function and HRCT scan and correlates with the quality of life score. There is no change in FE(NO) parameters at exacerbation and following treatment. Peripheral airway NO is elevated and reflects disease severity in bronchiectasis but does not provide information to inform acute treatment decisions.


Antagonistic trait of Lactobacillus reuteri S5 against Salmonella enteritidis and assessment of its potential probiotic characteristics.
Salmonella enteritidis is an important foodborne pathogen that has caused multiple outbreaks of infection associated with poultry and egg consumption. Thus, the prevention and inhibition of Salmonella enteritidis infection are of great concern. Lactic acid bacteria have anti-pathogenic activity; however, their underlying mechanisms and modes of action have not yet been clarified. In this study, the antibacterial mechanism of Lactobacillus reuteri S5 (L. reuteri S5) against Salmonella enteritidis ATCC13076 (S. enteritidis ATCC13076) was studied by different methods. We found that L. reuteri S5 was able to form a stable biofilm formation, colonizing the entire intestinal tract of chickens. In addition, bacterial cultures and the cell-free supernatant (CFS) of L. reuteri S5 inhibited SE ATCC13076 growth, and this growth inhibition was also observed in the co-culture assay. This effect may be predominantly caused by antimicrobial metabolites produced by L. reuteri S5. Furthermore, treatment with the CFS of L. reuteri S5 resulted in a significant reduction in the expression of Salmonella virulence, motility and adhesion genes and a significant reduction in the motility ability and inhibitory effect on biofilm formation. In addition, the damage to the membrane structure and intracellular structure induced by the CFS of L. reuteri S5 could be observed on Transmission electron microscopy images and dodecyl sulfate, sodium salt (SDS)-Polyacrylamide gel electrophoresis confirmed the disruptive action of the CFS of L. reuteri S5 on the cytoplasmic membrane. Our findings demonstrate that L. reuteri S5, an intestinal Lactobacillus species associated with chicken health, is able to form biofilm and stably colonize chicken intestines. It also possesses anti-SE activity, preventing SE growth, inhibits the expression of SE genes involved in adhesion and invasion, virulence and cell membrane integrity, inhibits SE biofilm formation and motility, damages or destroys bacterial structures, and inhibits intracellular protein synthesis. L. reuteri S5 therefore has potential applications as a probiotic agent.


Secondary pituitary insufficiency: report of three cases of ectopia or hemiagenesis of the thyroid gland.
Three patients with clinical and laboratory manifestations suggestive of pituitary insufficiency due to the presence of a pituitary tumor were found to have long-standing myxedema. The insidious appearance of the signs of hypothyroidism was explained by the cause of their disease--an ectopic thyroid gland in two patients and hemiagenesis of the thyroid in the third. Early recognition and treatment of such cases is important.


Left atrial diameter is a simple indicator of a deficiency in atrial natriuretic peptide secretion in patients with mitral stenosis: efficacy of postoperative supplementation with synthetic human alpha-atrial natriuretic peptide.
With regard to a deficiency in atrial natriuretic peptide (ANP) secretion, the relationship between plasma ANP and left atrial diameter measured by echocardiography was examined and the efficacy of postoperative supplementation was evaluated. (1) Ninety-six patients with mitral valve disease from 1997 to 2002 (M:F = 65:31, mean-age 65.3 +/- 8.9 years) were studied for relationship analyses. (2) Twenty-six patients with mitral stenosis and left atrial diameter > or = 60 mm undergoing mitral valve replacement (M:F = 17:9, mean-age 67.4 +/- 7.5 years) were randomly allocated to one of two groups; ANP-treated group (n = 13, 0.05 microg/kg/min of synthetic human alpha-ANP was postoperatively administered) and Control group (n = 13). (1) There were significant positive correlations between left atrial diameter and plasma renin-activity (r = 0.690, P < 0.01) and between left atrial diameter and plasma aldosterone (r = 0.757, P < 0.01). The maximum value of plasma ANP was 249.5 pg/mL accompanied with 56.2 mm of left atrial diameter in 29 patients suffering from mitral stenosis. There was a significant negative correlation between left atrial diameter and ANP in patients with left atrial diameter > 56.2 mm (r = - 0.725, P < 0.0001), whereas there was a significant positive correlation in patients with left atrial diameter < or = 56.2 mm (r = 0.529, P = 0.0066). (2) At 24 hours after operation, the ANP-treated group showed significantly lower plasma renin-activity (9.2 +/- 3.3 versus 36.2 +/- 7.4 ng/mL/h) and aldosterone (113.6 +/- 36.9 versus 473.8 +/- 95.8 pg/mL) than the Control group. Left atrial diameter can be a simple and useful indicator of a deficiency in endogenous ANP secretion in patients with mitral stenosis, and postoperative ANP supplementation contributes to suppressing further activation of renin-angiotensin system during the immediate postoperative period.


The Development of a Social Networking-Based Relatedness Intervention Among Young, First-Time Blood Donors: Pilot Study.
Increasing repeat blood donation behavior is a critical public health goal. According to self-determination theory, the process of developing internal motivation to give blood and an associated self-identity as a blood donor may be promoted by feelings of "relatedness" or a connection to other donors, which may be enhanced through social relations and interactions. The purpose of this report it to describe the development and pilot testing of a social networking-based (Facebook) intervention condition designed to increase feelings of relatedness via virtual social interaction and support. To develop the intervention condition content, images, text, polls, and video content were assembled. Ohio University college students (N=127) rated the content (82 images/text) presented by computer in random order using a scale of one to five on various dimensions of relatedness. Mean ratings were calculated and analyses of variance were conducted to assess associations among the dimensions. Based on these results, the relatedness intervention was adapted and evaluated for feasibility, acceptability, and preliminary efficacy among 24 first-time donors, aged 18 to 24 years, in a 30-day pilot trial. Paired t-tests were conducted to examine change over time in relatedness and connectedness. The intervention condition that was developed was acceptable and feasible. Results of the uncontrolled, preintervention, and postintervention evaluation revealed that feelings of individual-level relatedness increased significantly after the intervention. By promoting first-time blood donor relatedness, our goal is to enhance internal motivation for donating and the integration of the blood donor identity, thus increasing the likelihood of future repeat donation. ClinicalTrials.gov NCT02717338; https://clinicaltrials.gov/ct2/show/NCT02717338 (Archived by WebCite at http://www.webcitation.org/6ymHRBCwu)


Axonal degeneration affects muscle density in older men and women.
Using data from InCHIANTI, a prospective population-based survey of older persons, we examined the relationship of peroneal nerve conduction velocity (NCV, a measure of nerve myelination) and compound muscle action potential (CMAP, a measure of axonal degeneration) with calf muscle mass and density, two complementary measures of sarcopenia. NCV and CMAP were assessed by surface electroneurography of the right peroneal nerve conducted in 1162 participants, 515 men and 647 women, age 21-96 years, free of major neurological diseases. Cross-sectional muscle area and calf muscle density were measured using peripheral quantitative computerized tomography (pQCT). Both nerve and muscle parameters declined with age although in most cases the decline was not linear. In both sexes, CMAP, but not NCV, was independently and significantly associated with calf muscle density. These findings suggest that intrinsic changes in the muscle tissue are partially caused by a reduction in the number of motor axons.


Incidence, Predictors, and Outcomes of Acute Kidney Injury in Patients Undergoing Transcatheter Aortic Valve Replacement: Insights From the Society of Thoracic Surgeons/American College of Cardiology National Cardiovascular Data Registry-Transcatheter Valve Therapy Registry.
[Figure: see text].


Clinical outcomes of bilateral implantation of new generation monofocal IOL enhanced for intermediate distance and conventional monofocal IOL in a Korean population.
To compare the clinical outcomes of bilateral implantation of enhanced intermediate function intraocular lenses (IOLs) and standard monofocal IOLs. In this prospective, randomized, comparative controlled study, we compared the visual outcomes of patients who underwent bilateral cataract surgery at the Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, with either enhanced monofocal IOLs (Tecnis Eyhance, ICB00, Johnson and Johnson Vision Care, Inc) (Group 1) or standard monofocal IOLs (Tecnis, ZCB00, Johnson and Johnson Vision Care, Inc) (Group 2). The assessment included monocular and binocular uncorrected distance visual acuity (UDVA), uncorrected intermediate (UIVA at 60 cm) and near (UNVA at 40 cm) visual acuity, uncorrected defocus curves, contrast sensitivity testing (CST), and reading speed test using Quality of vision was evaluated using the Visual Function Questionnaire (VFQ-25). At 3-months postoperatively, monocular and binocular outcomes of UIVA and UNVA were statistically significantly better in Group 1 (P < 0.05). The binocular uncorrected defocus curve of Group 1 showed statistically significantly better outcomes at vergence ranges of -1.5 to -4.0 D (P < 0.05). Significantly higher reading speed test was also observed in Group 1 in all ranges tested (1.0 to 0.1 LogMAR) (P < 0.05). There were no statistically significant differences in CST between groups. Bilateral implantation of enhanced monofocal IOLs provided better vision at intermediate and near distances compared to standard monofocal IOLs, while maintaining good distance vision and contrast sensitivity.


Interval laparoscopic appendectomy after antibiotic therapy for appendiceal abscess in elderly patients.
The aim of this study was to evaluate the safety and efficacy of interval laparoscopic appendectomy after antibiotic therapy in elderly patients with appendiceal abscess. We retrospectively analyzed data for 50 patients with appendiceal abscess aged ≥18 years who had initially planned to undergo interval laparoscopic appendectomy after antibiotic therapy and 50 patients with appendicitis aged ≥70 years who had undergone early laparoscopic appendectomy. All patients were treated at the National Hospital Organization Kumamoto Medical Center between 2012 and 2018. We compared perioperative outcomes after interval appendectomy between patients aged <70 years and ≥70 years. Clinical progression of appendicitis during antibiotic therapy developed in one patient (2.0%), and recurrent appendicitis after antibiotic therapy for appendiceal abscess occurred in two patients (4.0%). Pathological findings confirmed appendiceal neoplasms in four patients (8.0%). Postoperative infectious complications occurred in 1 of 47 patients (2.1%) who had undergone successful interval laparoscopic appendectomy, and the median length of postoperative hospital stay was 4 days (interquartile range, 3-5 days). There were no significant differences in outcomes after interval appendectomy between patients aged <70 years and ≥70 years. In the secondary analysis, the median length of postoperative hospital stay after interval laparoscopic appendectomy for appendiceal abscess (4 days) was significantly shorter than that after early laparoscopic appendectomy for uncomplicated appendicitis (7 days; P < .001). Interval laparoscopic appendectomy for appendiceal abscess may be safe and effective in elderly patients without severe comorbidities. Interval appendectomy may be necessary for determining the underlying cause of appendiceal abscess in adults.


Physicians' attitudes toward guidelines for the treatment of hospitalized nursing home-acquired pneumonia.
To assess physician awareness, attitudes, and barriers toward the 2005 American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) guidelines for the treatment of hospitalized nursing home-acquired pneumonia (NHAP). We conducted a cross-sectional survey of 522 health care providers. The survey assessed the practice setting characteristics, physicians' attitudes, and reported awareness of the 2005 ATS/IDSA guidelines. Factor analysis was conducted to identify scales of variables, and a reliability analysis was performed to verify the reliability of the identified scales. Three hundred and ten completed the survey. Most responders (88%) reported familiarity with the practice guidelines in their field, but less than half were familiar with the ATS/IDSA NHAP guidelines. Although attitude scores regarding clinical practice guidelines did not differ significantly among various disciplines (P = .63), there were 2 characteristics that correlated with positive attitudes toward the 2005 ATS/IDSA guidelines in a multivariate analysis: being a pulmonary specialist (P ≤ .001) and time spent on CME activity per month (P = .03). The main barriers to the 2005 ATS/IDSA guidelines implementation were lack of awareness, concerns about practicality of using the recommended regimens, increased cost, lack of documented improved outcomes, and potential conflict with other guidelines. The study indicates low levels of awareness with the 2005 ATS/IDSA guidelines for treatment of hospitalized NHAP. Targeted intervention efforts including outcome assessment and cost-effective analysis may be necessary to improve adherence with the proposed guidelines.


TAS1R2 rs35874116 and TRPM5 rs886277 polymorphisms are not related with risk of obesity.
Obesity is one of the most serious public health problems due to its high morbidity and mortality rates. The taste perception is a powerful factor affecting food acceptance and may be one of the causes of tendency to obesity. Genetic variations in TAS1R2 and TRPM5 genes that affect taste preferences may cause inter-individual differences in food selection and thus increase the risk of obesity. We hypothesised that genetic variations in TAS1R2 and TRPM5 genes may contribute to obesity phenotypes by influencing food intake and body mass index (BMI). The aim of this study is to analyse the association of TAS1R2 rs35874116 and TRPM5 rs886277 polymorphisms with BMI and obesity. A total of 186 people were enrolled in this study, 54 of whom were normal weight (BMI = 18.50-24.99 kg/m2 ), 15 overweight (BMI = 25.0-29.9 kg/m2 ) and 117 obese people (BMI ≥ 30 kg/m2 ). Genomic DNA was isolated from whole blood with the Blood DNA Isolation kit. TAS1R2 rs35874116 and TRPM5 rs886277 polymorphisms were detected by using the Kompetitive Allele Specific PCR genotyping system (KASP). KASP genotyping assays are based on competitive allele-specific PCR and enable bi-allelic scoring of single nucleotide polymorphisms (SNPs) at specific loci. There were no significant differences in the allele and genotype frequencies between normal and overweight/obese, but there was a trend towards a smaller increase in BMI in TAS1R2 rs35874116 GA heterozygotes (OR = 1.827), GG (OR = 1.364) homozygotes genotypes. Although TAS1R2 and TRPM5 genes were associated with taste preferences in previous studies, we found out that TAS1R2 rs35874116 and TRPM5 rs886277 variants are not associated with obesity. The functional potency of the genetic variants within TAS1R2 and TRPM5 may be different between ethnic groups and this requires further investigations.


Selective activation of peroxymonosulfate govern by B-site metal in delafossite for efficient pollutants degradation: Pivotal role of d orbital electronic configuration.
Radical and non-radical oxidation pathways have been universally validated in transition metals (TMs) oxides activated peroxymonosulfate (PMS) processes. However, achieving high efficiency and selectivity of PMS activation remains challenging due to the ambiguous tuning mechanism of TMs sites on PMS activation in thermodynamic scope. Herein, we demonstrated that the exclusive PMS oxidation pathways were regulated by d orbital electronic configuration of B-sites in delafossites (CuBO2) for Orange I degradation (CoIII 3d6 for reactive oxygen species (ROSs) vs. CrIII 3d3 for electron transfer pathway). The d orbital electronic configuration was identified to affect the orbital overlap extent between 3d of B-sites and O 2p of PMS, which induced B-sites offering different types of hybrid orbital to coordinate with O 2p of PMS, thereby forming the high-spin complex (CuCoO2@PMS) or the low-spin complex (CuCrO2@PMS), on which basis PMS was selectively dissociated to form ROSs or achieve electron transfer pathway. As indicated by thermodynamic analysis, a general rule was proposed that B-sites of less than half-filled 3d orbital tended to act as electron shuttle, i.e., CrIII (3d3), MnIII (3d4), interacting with PMS to execute an electron transfer pathway for degrading Orange I, while B-sites of between half-filled and full-filled 3d orbital preferred to be electron donator, i.e., CoIII (3d6), FeIII (3d5), activating PMS to generate ROSs. These findings lay a foundation for the oriented design of TMs-based catalysts from the atomic level according to d orbital electronic configuration optimization, as so to facilitate the achievement of PMS-AOPs with highly selective and efficient remediation of contaminants in water purification practice.


Effect of sea surface temperature and precipitation on annual frequency of harmful algal blooms in the East China Sea over the past decades.
Coastal harmful algal blooms (HABs) in China's seas have attracted researchers' attention for decades. Among the four seas of China, the HAB frequency is the highest in the East China Sea (ECS). The impact of climate change and anthropogenic dominant factors on HABs is not well quantified and the response of HABs to the changing climate is also not clear. Here, we compiled a time series of observation-based HAB events since the 1980s and performed a regional assessment to elucidate the dominant drivers of HAB events in the ECS. The results showed that the increase in the frequency of HAB events in the ECS between 2000 and 2003 was associated with increases in dissolved inorganic phosphorus and sea surface temperature anomalies as well as decreasing summer precipitation. The declining annual frequency in HAB events in the ECS after 2003 was associated with the two climatological factors, most notably, precipitation. Under the "business-as-usual" scenario, climate change will increase the annual HAB events in the ECS from the historical frequency (1985-2013) by more than five-fold by the end of 21st century. These findings demonstrated that management strategies based on reducing nutrient loading also need to consider the effects of climate change in the future.


[Functional reserves of the cardiovascular system in 15-16-year-old girls].
Adaptative cardiovascular responses were examined in 15-16-year-old girls during exercises and higher motivation. The latter promotes the optimization, rationalization, and effectiveness of cardiac performance and the mobilization of the body's functional reserves.


Robot-assisted laparoscopic vesicule prostatectomy for mixed epithelial-stromal tumor of seminal vesicle.
Mixed epithelial-stromal tumor is a biphasic tumor with stromal and benign epithelial components. Only 40 cases of mixed epithelial-stromal tumor originating from a seminal vesicle have previously been published in English. A 52-year-old man was transferred to our hospital for evaluation of a 3.0-cm pelvic tumor detected incidentally by computed tomography. Robot-assisted laparoscopic vesicle prostatectomy was performed. We approached the Retzius space from both levels of the pouch of Douglas and peritoneal top of the bladder to clarify the tumor's environment. Pathologically, the tumor was diagnosed as a low-grade mixed epithelial-stromal tumor originating from the right seminal vesicle. There was no evidence of disease recurrence within 51 months. This is the first report of robot-assisted laparoscopic vesicle prostatectomy for a seminal vesicle mixed epithelial-stromal tumor. Long-term observation is warranted due to the lack of reports with sufficient follow-up to ensure the procedure's safety.


In silico identification of SARS-CoV-2 cell entry inhibitors from selected natural antivirals.
The aim of this study is to identify potential drug-like molecules against SARS-CoV-2 virus among the natural antiviral compounds published in the Encyclopedia of Traditional Chinese Medicine. To test inhibition capability of these compounds first, we docked them with Spike protein, angiotensin-converting enzyme 2 (ACE2) (PDB ID: 6M0J) and neuropilin 1 (NRP1) (PDB ID: 7JJC) receptors, and found significant docking scores with extra precision up to -11 kcal/mol. Then, their stability in the binding pockets were further evaluated with molecular dynamics simulation. Eight natural antiviral compounds were identified as potential inhibitors against SARS-CoV-2 cell entry after 200 ns molecular dynamics simulations. We found CMP-3, CMP-4, CMP-5, CMP-6 and CMP-8 are strong binders for the spike protein, CMP-1, CMP-2, CMP-4, CMP-5 and CMP-7 are strong binders for the neuropilin receptor, and CMP-5 is a strong binder for the ACE2. Quercetin derivatives (CMP-4, CMP-5, CMP-6 and CMP-7) were found highly stable in the active domain of NRP1, ACE2 and Spike protein. Especially, CMP-5 showed an inhibitory activity for all targets. These natural antivirals may be potential drug candidates for the prevention of SARS-CoV-2 infection.


Teledermatology: a review of reliability and accuracy of diagnosis and management.
In this article, the authors summarize the published literature on the reliability and accuracy of teledermatology. The first section reports on the diagnostic reliability of teledermatology compared with face-to-face clinic consultation. In the second section, the authors report on the "intragroup" diagnostic agreement between either clinic dermatologists or teledermatologists. The third section discusses the diagnostic accuracy for those studies that include definitive histopathologic diagnosis. The last section summarizes the literature comparing clinical management decisions by clinic dermatologists to those made by teledermatologists.


Genetic findings of Sanger and nanopore single-molecule sequencing in patients with X-linked hearing loss and incomplete partition type III.
POU3F4 is the causative gene for X-linked deafness-2 (DFNX2), characterized by incomplete partition type III (IP-III) malformation of the inner ear. The purpose of this study was to investigate the clinical characteristics and molecular findings in IP-III patients by Sanger or nanopore single-molecule sequencing. Diagnosis of IP-III was mainly based on clinical characteristics including radiological and audiological findings. Sanger sequencing of POU3F4 was carried out for these IP-III patients. For those patients with negative results for POU3F4 Sanger sequencing, nanopore long-read single-molecule sequencing was used to identify the possible pathogenic variants. Hearing intervention outcomes of hearing aids (HAs) fitting and cochlear implantation (CI) were also analyzed. Aided pure tone average (PTA) was further compared between two groups of patients according to their different locations of POU3F4 variants: in the exon region or in the upstream region. In total, 18 male patients from 14 unrelated families were diagnosed with IP-III. 10 variants were identified in POU3F4 by Sanger sequencing and 6 of these were reported for the first time (p.Gln181*, p.Val215Gly, p.Arg282Gln, p.Gln316*, c.903_912 delins TGCCA and p.Arg205del). Four different deletions that varied from 80 to 486 kb were identified 876-1503 kb upstream of POU3F4 by nanopore long-read single-molecule sequencing. De novo genetic mutations occurred in 21.4% (3/14) of patients with POU3F4 mutations. Among these 18 patients, 7 had bilateral HAs and 10 patients received unilateral CI. The mean aided PTA for HAs and CI users were 41.1 ± 5.18 and 40.3 ± 7.59 dB HL respectively. The mean PTAs for patients with the variants located in the exon and upstream regions were 39.6 ± 6.31 versus 43.0 ± 7.10 dB HL, which presented no significant difference (p = 0.342). Among 14 unrelated IP-III patients, 28.6% (4/14) had no definite mutation in exon region of POU3F4. However, possible pathogenic deletions were identified in upstream region of this gene. De novo genetic mutations occurred in 21.4% (3/14) of patients with POU3F4 mutation. There was no significant difference of hearing intervention outcomes between the IP-III patients with variants located in the exon region and in the upstream region.


Rate of torque development is the primary contributor to quadriceps avoidance gait following total knee arthroplasty.
Following rehabilitation for total knee arthroplasty, "quadriceps avoidance gait", defined by limited knee flexion angle excursion during walking, persists and contributes to poor long-term outcomes. Given the presence of several post-surgical impairments, identifying the contribution of multiple factors to knee flexion angle excursion is important to developing targeted interventions to improve recovery after total knee arthroplasty. Which outcomes continue to improve following rehabilitation for total knee arthroplasty? What are the primary contributors to impaired knee flexion angle excursion during walking following total knee arthroplasty? Peak muscle strength and rate of torque development of the quadriceps, hip abductors, and hip external rotators, five-time sit-to-stand test, Knee Injury & Osteoarthritis Outcome Score, and gait mechanics were assessed in 24 participants at three and six months post-surgery. Paired sample t-tests or Wilcoxon Signed-Rank tests were used to compare outcomes between assessments. Stepwise multiple linear regression were used to assess the contribution of each measure to knee flexion angle excursion. Significant improvements were noted in all outcomes except hip external rotation rate of torque development, gait speed, and knee flexion angle excursion. Quadriceps rate of torque development and knee pain significantly contributed to knee flexion angle excursion at three months (Adjusted R2 = 0.342), while quadriceps rate of torque development and peak hip external rotation strength significantly contributed at six months (Adjusted R2 = 0.436). While higher pain levels at three months and greater peak hip external rotation muscle strength at six months contribute to impaired knee flexion angle excursion, quadriceps rate of torque development was the primary contributor to knee flexion angle excursion at both three and six months after surgery. Implementing strategies to maximize quadriceps rate of torque development during rehabilitation may help to reduce quadriceps avoidance gait after total knee arthroplasty.


Occurrence of per- and polyfluoroalkyl substances in aquatic environments and their removal by advanced oxidation processes.
Per- and polyfluoroalkyl substances (PFAS), one of the main categories of emerging contaminants, are a family of fluorinated organic compounds of anthropogenic origin. PFAS can endanger the environment and human health because of their wide application in industries, long-term persistence, unique properties, and bioaccumulation potential. This study sought to explain the accumulation of different PFAS in water bodies. In aquatic environments, PFAS concentrations range extensively from <0.03 (groundwater; Melbourne, Australia) to 51,000 ng/L (Groundwater, Sweden). Additionally, bioaccumulation of PFAS in fish and water biota has been stated to range from 0.2 (Burbot, Lake Vättern, Sweden) to 13,900 ng/g (Bluegill samples, U.S.). Recently, studies have focused on PFAS removal from aqueous solutions; one promising technique is advanced oxidation processes (AOPs), including microwaves, ultrasound, ozonation, photocatalysis, UV, electrochemical oxidation, the Fenton process, and hydrogen peroxide-based and sulfate radical-based systems. The removal efficiency of PFAS ranges from 3% (for MW) to 100% for UV/sulfate radical as a hybrid reactor. Therefore, a hybrid reactor can be used to efficiently degrade and remove PFAS. Developing novel, efficient, cost-effective, and sustainable AOPs for PFAS degradation in water treatment systems is a critical area of research.


Effects of Obligate Heterofermentative Lactic Acid Bacteria Alone or in Combination on the Conservation of Sugarcane Silage.
Our objective was to determine the effects of two strains of obligate heterofermentative bacteria, alone or in combination, on the fermentation profile, gas production kinetics, chemical composition, and aerobic stability of sugarcane silage. A plot of sugarcane was manually harvested, mechanically chopped and treated with: distilled water (5 mL kg-1; Control), Lentilactobacillus hilgardii CNCM I-4785 [3 × 105 colony-forming units (cfu) g-1; LH], Lentilactobacillus buchneri NCIMB 40788 (3 × 105 cfu g-1; LB), and LH+LB (1.5 × 105 cfu g-1 of each strain). Treated forages were packed into 1.96-L gas-tight silos (0.40 porosity) and stored at 25 ± 1.5°C for 70 days (4 replicates per treatment). All heterolactic inoculants were effective to increase acetic acid concentration and inhibit yeast metabolism, as treated silages had lower formation of ethanol, ethyl esters and gas during fermentation. Lower fungal development spared soluble carbohydrates, consequently resulting in silages with higher in vitro digestibility. Nevertheless, L. buchneri was the most effective strain to extend the aerobic stability of sugarcane silage (based on both temperature and pH rise). The use of L. buchneri alone or in combination with L. hilgardii, applied at 3 × 105 cfu g-1, is a feasible strategy to inhibit yeast metabolism and increase the nutritional quality of sugarcane silage.


Effects of ergot drugs on serotonergic function: behavior and neurochemistry.
Several new ergot drugs were tested for behavioral and neurochemical effects related to serotonergic function. Lergotrile and bromocriptine potentiated the so-called "5-HT syndrome", a set of behaviours associated with increased serotonergic neurotransmission consequent to monoamine oxidase inhibition and tryptophan loading. Metergoline antagonized this behavior. In studies of receptor binding using 3H-5-HT or 3H-LSD, metergoline was the most potent at displacing specific ligand binding. Since the ergots also affect dopaminergic function, these results are discussed for their information on both dopaminergic and serotonergic actions of these drugs and their implications for clinical use of ergots.


Enzymes of phospholipid metabolism in rat pancreatic islets: subcellular distribution and the effect of glucose and calcium.
The effect of glucose and calcium on the activities of the phosphatidylinositol cycle enzymes, CDP-diglyceride inositol transferase, diacylglycerokinase, and lysophosphatidylcholine 2-acyltransferase in rat pancreatic islets was studied. Calcium inhibited the activity of CDP-diglyceride inositol transferase but had no effect on lysophosphatidylcholine 2-acyltransferase and diacylglycerokinase activities. Upon preincubation of islets in a concentration of glucose known to stimulate insulin release, the activity of lysophosphatidylcholine 2-acyltransferase, but not that of diacylglycerokinase or the CDP-diglyceride inositol transferase, was stimulated. Subcellular fractionation of pancreatic islets showed that secretory granule membranes were enriched in CDP-diglyceride inositol transferase, whereas lysophosphatidylcholine 2-acyltransferase activity was highest in the microsomal membranes. The activation of 2-acyltransferase by incubating islets in insulinotropic glucose, and the calcium sensitivity of CDP-diglyceride inositol transferase, suggest that these enzymes may have roles in regulation of insulin secretion.


Cast bracing in practice: a two-year study in Aberdeen.
This paper reviews the use of cast bracing of fractures of the femoral shaft over a two-year period in an orthopaedic unit which provides a service to half a million people in the Grampian Region. More than three-quarters of the patients with fractures of the femoral shaft admitted to hospital were treated by cast bracing and these patients are reviewed. In 1976 the cast braces were applied at an average of 6.3 weeks after fracture and in 1977 after an average of 5 weeks, with consequent savings in hospital bed time. The average time to union remained remarkably constant at around 14.5 weeks. The less than good results are looked at critically with a view to avoiding these in the future.


Experience from community based childhood burn prevention programme in Bangladesh: implication for low resource setting.
A comprehensive community-based burn prevention framework was developed for rural Bangladesh taking into consideration the magnitude, consequences of burns, risk factors of childhood burn, health seeking behaviour of parents after a burn injury of a child and the perception of community people. This paper explains the comprehensive framework of the childhood burn prevention programme and describes its acceptability, feasibility and sustainability. A number of methodologies were adopted in developing the framework, such as, (i) building up relevant information on childhood burn and prevention methods, (ii) arranging workshops and consultation meetings with experts and related stakeholders and (iii) piloting components of the framework on a small scale. Lack of supervision of the children, hazardous environment at home and the low level awareness about childhood burn and other injuries were identified as the major attributes of childhood burn in Bangladesh. To address these factors "Triple S" strategies were identified for the prevention framework. These strategies are: Safe environment. Supervision. Skill development. According to these strategies, home safety, community crèche, school safety, formation of community groups and general awareness activities were identified as the different components of the childhood burn prevention framework in rural Bangladesh. The framework was piloted in a small scale to explore its feasibility acceptability and sustainability. The framework was found to be acceptable by the community. It is also expected to be feasible and sustainable as very low cost and locally available technology and resources were utilized in the framework. Large scale piloting is necessary to explore its effectiveness and ability to scale up all over the whole country.


Stages of change in hearing-protection behavior, cognition, and hearing status.
To determine stages of hearing-protection behavioral change and their relationships with cognitions and hearing status. A cross-sectional study of 769 construction workers who completed a survey and audiometric tests. The majority of participants (over 64%) were in the preparation stage. Participants in the action/maintenance stage demonstrated significantly greater benefits, self-efficacy, and interpersonal influence; fewer barriers; and better hearing. This is the first study that shows significantly better health outcome, hearing ability, as the stage progresses. Study demonstrates preliminary validity of the stages of change with hearing-protection behavior. Future hearing-protection intervention should integrate the stages of change to increase effectiveness.


Transvenous excimer laser-assisted lead extraction of cardiac implantable electrical devices in the Japanese elderly population.
The feasibility and safety of lead extraction of cardiac implantable electronic devices (CIEDs) in the elderly Asian population remain uncertain. We report the outcome and safety of transvenous excimer laser-assisted lead extraction of CIEDs in Japanese patients aged ≥80 years. Consecutive 235 patients (age 67±15 years, 167 male) undergoing lead extraction of CIED with an excimer laser system (Philips, Andover, MA, USA) were included. Of 235 consecutive patients, 51 (22%) were ≥80 years (age 86±5 years, 14 were aged ≥90 years; 42 had pacemakers, 3 had implantable cardioverter defibrillators, and 6 had cardiac resynchronization therapy devices). The median implant duration was 110±95 months. Patients aged ≥80 years had lower body mass index (BMI, 20.7±3.1kg/m2 vs. 22.6±3.4kg/m2, p<0.001), higher incidence of CIED infection (98% vs. 63%, p<0.010), and longer duration of hospitalization (31±17 days vs. 24 ± 31 days, p<0.001) than patients aged <80 years. There were no differences between the age groups in the rate of complete retrieval (94.1% vs. 95.1%, p=0.726) and major complications, including cardiac tamponade and cardiogenic shock (2.0% vs. 2.7%, p=1.000). Excimer laser-assisted lead extraction was safe and feasible in the Japanese elderly population with low BMI, despite the high likelihood of procedural complications. Early removal of infected CIEDs should be performed without delay in elderly Asian populations.


Baseline high-resolution maps of organic carbon content in Australian soils.
We introduce a new dataset of high-resolution gridded total soil organic carbon content data produced at 30 m × 30 m and 90 m × 90 m resolutions across Australia. For each product resolution, the dataset consists of six maps of soil organic carbon content along with an estimate of the uncertainty represented by the 90% prediction interval. Soil organic carbon maps were produced up to a depth of 200 cm, for six intervals: 0-5 cm, 5-15 cm, 15-30 cm, 30-60 cm, 60-100 cm and 100-200 cm. The maps were obtained through interpolation of 90,025 depth-harmonized organic carbon measurements using quantile regression forest and a large set of environmental covariates. Validation with 10-fold cross-validation showed that all six maps had relatively small errors and that prediction uncertainty was adequately estimated. The soil carbon maps provide a new baseline from which change in future carbon stocks can be monitored and the influence of climate change, land management, and greenhouse gas offset can be assessed.


The impact of image processing algorithms on digital radiography of patients with metalic hip implants.
To investigate the impact of image processing algorithms on image quality of digital radiographs. This study was motivated from a case of a patient with metallic hip implant, where the anatomy around the implant was misrepresented, due to failure of the processing algorithm. A quality control phantom was imaged using a digital radiographic unit and the standard examination protocol for Pelvis anteroposterior (AP) projection. The original image was reprocessed with all available selections of Diamond View, which is a processing algorithm for optimizing image quality of different anatomic regions. The same procedure was repeated for two other examination protocols, Femur AP and Hip AP, which differ in terms of harmonization kernel and gain, and look up table settings. The whole procedure was repeated with a Pb strip, 2 cm wide and 3 mm thick, positioned close to the right phantom edge, in order to simulate a metallic hip implant. Using ImageJ a number of regions of interest (ROIs) were positioned on the phantom images and the impact of processing parameters on certain image characteristics and image quality indices was evaluated. Processing parameters have a strong impact on image characteristics, but in terms of image quality, differences between images with and without the implant are small. Exception is the regions in the vicinity of the implant, where larger differences, that could affect diagnosis, were observed. In case of doubt, additional processing with settings which minimize the risk of anatomic misrepresentation should be used.


Dansyl cadaverine regulates ligand induced endocytosis of interleukin-8 receptor in human polymorphonuclear neutrophils.
Interleukin-8 (IL-8), a neutrophil chemotactic agent, acts as a key mediator in a large number of acute and chronic inflammatory diseases. At 37 degrees C, the receptor for IL-8 is rapidly internalized with its ligand. But no specific inhibitor of this ligand induced internalization of the receptor has been reported so far. We have found that monodansyl cadaverine (MDC) inhibited about 70% of IL-8 induced endocytosis and caused 70% and 66% inhibition of IL-8 mediated chemotaxis and respiratory burst response, respectively, in neutrophils. The uninternalized receptor was detected by anti IL-8R antibody in MDC treated cells. The endocytosis of IL-8R was strongly inhibited under Ca2+ depleted conditions which was restored on addition of 1 mM CaCl2 indicating the critical involvement of a Ca2+ ion in the process. Absence of receptor internalisation makes the MDC treated neutrophils suitable for studying the interaction of IL-8R with potential therapeutic agents e.g. for in vitro screening of anti-inflammatory agents.


Repeat-Associated Non-AUG Translation of AGAGGG Repeats that Cause X-Linked Dystonia-Parkinsonism.
X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disorder caused by the intronic insertion of a SINE-VNTR-Alu (SVA) retrotransposon carrying an (AGAGGG)n repeat expansion in the TAF1 gene. The molecular mechanisms by which this mutation causes neurodegeneration remain elusive. We investigated whether (AGAGGG)n repeats undergo repeat-associated non-AUG (RAN) translation, a pathogenic mechanism common among repeat expansion diseases. XDP-specific RAN translation reporter plasmids were generated, transfected in HEK293 cells, and putative dipeptide repeat proteins (DPRs) were detected by Western blotting. Immunocytochemistry was performed in COS-7 cells to determine the subcellular localization of one DPR. We detected putative DPRs from two reading frames, supporting the translation of poly-(Glu-Gly) and poly-(Arg-Glu) species. XDP RAN translation initiates within the (AGAGGG)n sequence and poly-(Glu-Gly) DPRs formed nuclear inclusions in transfected cells. In summary, our work provides the first in-vitro proof of principle that the XDP-linked (AGAGGG)n repeat expansions can undergo RAN translation. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


52-Year-Old With Epistaxis, Hemoptysis, Hoarseness, and Weight Loss.
A 52-year-old man presented with hemoptysis of 2 weeks' duration. He had been experiencing hoarseness, right-sided pleuritic chest pain, subjective fevers, chills, night sweats, and 10 pounds weight loss for the previous 2 months. He additionally reported severe frontal headaches, nasal congestion, and intermittent epistaxis, which had been present for a year before his current presentation. He had worked in construction and denied tobacco or illicit drug use.


Comparison of paclitaxel and everolimus-eluting stents in ST-segment elevation myocardial infarction and influence of thrombectomy on outcomes. ESTROFA-IM study.
We sought to compare the long-term clinical outcome of with ST-segment elevation myocardial infarction treated with paclitaxel-eluting stents or everolimus-eluting stents and the influence of thrombectomy on outcomes. The ESTROFA-IM is a multicenter retrospective registry collecting consecutive patients with infarction treated with these stents in 16 centers. Propensity-score matching was performed to select comparable stent groups and comparable groups with and without thrombectomy. After matching patients, 350 treated with everolimus-eluting stents and 350 with paclitaxel-eluting stents were included in the analysis. The clinical and angiographic characteristics were comparable in both groups. The 2-year incidence of death, infarction, and target lesion revascularization was 14.9% for paclitaxel-eluting stents and 11.5% for everolimus-eluting stents (P = .04) and the incidence of definite/probable thrombosis 4.3% and 1.4%, respectively (P = .01). The use of paclitaxel-eluting was an independent predictor for events (hazard ratio = 2.44, 95% confidence interval, 1.28-4.65; P = .006). The benefit of everolimus-eluting stents over paclitaxel-eluting stents regarding stent thrombosis was more evident in the nonthrombectomy subgroup (5.4% vs 1.4%; P = .01). A significant interaction was found in the subgroups with and without thombectomy in the comparison between paclitaxel-eluting stents and everolimus-eluting stents for the end-point of stent thrombosis (P = .039). The results of this multicenter registry suggest better clinical outcomes with the everolimus-eluting stents in ST-segment elevation myocardial infarction. The lower risk of thrombosis with these stents could be more relevant in the absence of thrombectomy.


Extended continuous-wave supercontinuum generation in a low-water-loss holey fiber.
We report on the development of a 2.5 microm core photonic crystal fiber with a substantially reduced water-peak loss around 1.38 microm, which allows extended Raman-soliton supercontinuum generation up to 1.55 microm with a cw ytterbium fiber laser pump source. The resulting broadband, high-spectral-power-density, low-coherence light source can be employed for advanced, submicrometer resolution optical coherence tomography.


Intracellular biopotentials during static extracellular stimulation.
Two properties of the intracellular potentials and electric fields resulting from static extracellular stimulation are obtained for arbitrarily shaped cells. First, the values of intracellular potential are shown to be bounded by the maximum and minimum values of extracellular potential on the surface of the cell. Second, the volume average of the magnitude of intracellular electric field is shown to have an upper bound given by the ratio of the magnitude of the largest extracellular potential difference on the surface of the cell to a generalized length constant lambda = [sigma(intra)V(cell)/(sigma(memb)A(cell))](1/2), where V(cell) and A(cell) are the volume and surface area of the cell, sigma(intra) is the intracellular conductivity (reciprocal ohms per centimeter), and sigma(memb) is the membrane conductivity (reciprocal ohms per square centimeter). The use of the upper bound on the volume average of the magnitude of intracellular electric field as an estimate for intracellular isopotentiality is discussed and the use of the generalized length constant for electrically describing arbitrary cells is illustrated for cylindrical- and spheroidal-shaped cells.


Trans-cinnamaldehyde nanoemulsion wash inactivates Salmonella Enteritidis on shelled eggs without affecting egg color.
Salmonella Enteritidis is a major foodborne pathogen that causes enteric illnesses in humans, primarily through the consumption of contaminated poultry meat and eggs. Despite implementation of traditional disinfection approaches to reduce S. Enteritidis contamination, egg-borne outbreaks continue to occur, raising public health concerns and adversely affecting the popularity and profitability for the poultry industry. Generally Recognized as Safe (GRAS) status phytochemicals such as Trans-cinnamaldehyde (TC) have previously shown to exhibit anti-Salmonella efficacy, however, the low solubility of TC is a major hurdle in its adoption as an egg wash treatment. Therefore, the present study investigated the efficacy of Trans-cinnamaldehyde nanoemulsions (TCNE) prepared with emulsifiers Tween 80 (Tw.80) or Gum Arabic and lecithin (GAL) as dip treatments, at 34°C, for reducing S. Enteritidis on shelled eggs in presence or absence of 5% chicken litter. In addition, the efficacy of TCNE dip treatments in reducing trans-shell migration of S. Enteritidis across shell barrier was investigated. The effect of wash treatments on shell color were evaluated on d 0, 1, 7, and 14 of refrigerated storage. TCNE-Tw.80 or GAL treatments (0.06, 0.12, 0.24, 0.48%) were effective in inactivating S. Enteritidis by at least 2 to 2.5 log cfu/egg as early as 1 min of washing time (P < 0.05). In presence of organic matter, nanoemulsions (0.48%) reduced S. Enteritidis counts by ∼ 2 to 2.5 log cfu/egg as early as 1 min, (P < 0.05). Nanoemulsion wash also inhibited trans-shell migration of S. Enteritidis, as compared to control (P < 0.05). The nanoemulsion wash treatments did not affect shell color (P > 0.05). Results suggest that TCNE could potentially be used as an antimicrobial wash to reduce S. Enteritidis on shelled eggs, although further studies investigating the effect of TCNE wash treatments on organoleptic properties of eggs are necessary.


[Epidemiology and risk factors of hepatocellular carcinoma].
The incidence of hepatocellular carcinoma (HCC) has increased over the past decades as a result of alcoholic liver disease, the metabolic syndrome and the increasing incidence of viral hepatitis B and C. An evaluation of the epidemiology of HCC, presentation and discussion of the risk factors for the development of HCC. This study was based on a literature review, analysis of the statistics of the World Health Organization (WHO), discussion of current basic research and expert recommendations. The results show that HCC already represents the fifth most common malignancy in men and the ninth most common malignancy in women, and the incidence is still rising. The pronounced regional differences in prevalence and underlying risk factors are mainly, but not exclusively, due to the prevalence of chronic viral hepatitis B. Hepatocellular carcinoma is a major medical problem. Primary prevention measures and suitable screening algorithms are gaining more and more importance.


The use of mrp1-deficient (Danio rerio) zebrafish embryos to investigate the role of Mrp1 in the toxicity of cadmium chloride and benzo[a]pyrene.
Previous studies in our lab have revealed that both P-glycoprotein (Pgp) and multi-resistance associated protein (Mrp) 1 played important roles in the detoxification of heavy metals and polycyclic aromatic hydrocarbon (PAH) in zebrafish embryos. This paper aims to extend this research by using mrp1-deficient model to illustrate the individual function of Mrp1. In this respect, CRISPR/Cas9 system was employed to generate a frameshift mutation in zebrafish mrp1 causing premature translational stops in Mrp1. Significant reduction on the efflux function of Mrps was found in mutant zebrafish embryos, which correlated well with the significantly enhanced accumulation and toxicity of cadmium chloride (CdCl2) and benzo[a]pyrene (BαP), indicating the protective role of the corresponding protein. The different alteration on the accumulation and toxicity of Cd2+ and BαP could be attributed to the fact that Cd2+ and its metabolites were mainly excreted by Mrp1, while BαP was primarily pumped out by Pgp. More importantly, the compensation mechanism for the absence of Mrp1, including elevated glutathione (GSH) level and up-regulated expression of pgp and mrp2 were also found. Thus, mrp1-deficient zebrafish embryo could be a useful tool in the investigation of Mrp1 functions in the early life stages of aquatic organisms. However, compensation mechanism should be taken into consideration in the interpretation of results obtained with mrp1-deficient fish.


mrMLM v4.0.2: An R Platform for Multi-locus Genome-wide Association Studies.
Previous studies have reported that some important loci are missed in single-locus genome-wide association studies (GWAS), especially because of the large phenotypic error in field experiments. To solve this issue, multi-locus GWAS methods have been recommended. However, only a few software packages for multi-locus GWAS are available. Therefore, we developed an R software named mrMLM v4.0.2. This software integrates mrMLM, FASTmrMLM, FASTmrEMMA, pLARmEB, pKWmEB, and ISIS EM-BLASSO methods developed by our lab. There are four components in mrMLM v4.0.2, including dataset input, parameter setting, software running, and result output. The fread function in data.table is used to quickly read datasets, especially big datasets, and the doParallel package is used to conduct parallel computation using multiple CPUs. In addition, the graphical user interface software mrMLM.GUI v4.0.2, built upon Shiny, is also available. To confirm the correctness of the aforementioned programs, all the methods in mrMLM v4.0.2 and three widely-used methods were used to analyze real and simulated datasets. The results confirm the superior performance of mrMLM v4.0.2 to other methods currently available. False positive rates are effectively controlled, albeit with a less stringent significance threshold. mrMLM v4.0.2 is publicly available at BioCode (https://bigd.big.ac.cn/biocode/tools/BT007077) or R (https://cran.r-project.org/web/packages/mrMLM.GUI/index.html) as an open-source software.


A quantitative evaluation of adherence and inhalation technique among respiratory patients: An observational study using an electronic inhaler assessment device.
Problems related to poor adherence and inhaler technique (IT) are historically reported in the literature. Most common methods used for adherence and IT assessment are reported to be either inaccurate or subjective. Few electronic monitoring devices (EMDs) that provide an objective measure of both adherence and IT while patients use inhalers at home now exist. Therefore, this study aimed to examine adherence level and IT among respiratory patients in community care using such an EMD for the first time in England. A prospective, multicentre, observational cohort study was conducted. Patients with chronic obstructive pulmonary disease (COPD) or asthma were recruited from independent community pharmacies within West and South London. Patients were provided with a dry-powder inhaler (DPI) mounted with an EMD to use for 1 month. Adherence was also assessed using pharmacy dispensing data, inhaler dose counter and self-reporting. Data were available for 48 patients. Only eight patients used their inhaler in the correct manner at the correct interval as identified by the chosen EMD. The median actual adherence rate, as measured by the EMD, was 42.7%. This was significantly different from the median dose counter adherence (100%), medication refill adherence (MRA) (100%), proportions of days covered (PDC) (97.8%) and self-reported adherence (P < .001, each). Within a 1-month period, there were 2188 files showing attempted use of the DPI, of which 840 had IT errors. The median technique error rate (TER) was 30.1%. Most common errors recorded were as follows: multiple inhalations, drug priming without inhalation and failure to prime the device correctly. The current study demonstrates that measures such as dose counter, prescription refill and self-reporting showed a high level of adherence among the observed patients. However, the objective data provided by the EMD showed a significantly lower actual adherence rate, reflecting how adherence remains variable and problematic among patients in the community.


Time for sperm eg(g)alitarianism?
The demand for certainty is one which is natural to man, but is nevertheless an intellectual vice -Bertrand Russell.


Ideal operating conditions for a variable stiffness transverse plane adapter for individuals with lower-limb amputation.
Transverse plane shear stress between the prosthetic socket and residual limb often results in soft tissue breakdown and discomfort for individuals with lower-limb amputation. To better understand the effects of reduced transverse plane stiffness in the shank of a prosthesis, a second-generation variable stiffness torsion adapter (VSTA II) was tested with individuals with a transtibial amputation (n = 10). Peak transverse plane moments, VSTA II deflection, range of whole body angular momentum (WBAM), ground reaction impulse, joint work, and personal stiffness preference were evaluated at three fixed stiffness levels (compliant: 0.25 Nm/°, intermediate: 0.75 Nm/°, stiff: 1.25 Nm/°) at three walking speeds (self-selected, fast and slow: +/- 20% of self-selected, respectively) while straight-line walking and performing left and right turns. Residual limb loading decreased and VSTA II displacement increased for reductions in stiffness and both metrics increased with increasing walking speed, while ground reaction impulse and joint work were unaffected. The range of WBAM increased with decreased stiffness, which suggests an increased risk of falling when using the VSTA II at lower stiffness settings. Preference testing showed no significant result, but trends for lower stiffness settings when turning and walking at self-selected speeds were noted, as were stiffer settings when walking straight and at faster speeds. These results show that a device with rotational compliance like the VSTA II could reduce loading on the residual limb during straight walking and turning activities and that factors such as walking speed, activity type and user preference can affect the conditions for optimal use.


Changes in emergency psychiatric consultations in time of COVID-19: a retrospective observational study in the Verona Academic Hospital over the two pandemic years 2020-2021.
During the first months of the COVID-19 pandemic, local health authorities in most Italian regions prescribed a reduction of ordinary outpatient and community mental health care. The aim of this study was to assess the impact of the COVID-19 pandemic on access to the emergency departments (ED) for psychiatric consultation in the pandemic years 2020 and 2021 compared to 2019. This is a retrospective study conducted by using routinely collected administrative data of the two EDs of the Verona Academic Hospital Trust (Verona, Italy). All ED psychiatry consultations registered from 01.01.2020 to 31.12.2021 were compared with those registered in the pre-pandemic year (01.01.2019 to 31.12.2019). The association between each recorded characteristic and the year considered was estimated by chi-square or Fisher's exact test. A significant reduction was observed between 2020 and 2019 (-23.3%) and between 2021 and 2019 (-16.3%). This reduction was most evident in the lockdown period of 2020 (-40.3%) and in the phase corresponding to the second and third pandemic waves (-36.1%). In 2021, young adults and people with diagnosis of psychosis showed an increase in requests for psychiatric consultation. Fear of contagion may have been an important factor in the overall reduction in psychiatric consultations. However, psychiatric consultations for people with psychosis and for young adults increased. This finding underlines the need for mental health services to implement alternative outreach strategies aimed to support, in times of crisis, these vulnerable segments of the population.


Complementary Public Service Announcements as a Strategy for Enhancing the Impact of Health-Promoting Messages in Fictional Television Programs.
Research suggests that health-promoting storylines in developed nations' fictional television programs can have a beneficial impact on viewers' beliefs, attitudes, intentions, or behaviors. The sizes of the effects are generally modest; however, the audience reach is substantial. Given that many fictional programs may hold the prolonged attention of millions of viewers, it is of value to examine potential strategies for enhancing the persuasive impact of their health-promoting storylines. Complementary public service announcements may be a promising strategy. This randomized experimental study (N = 310) examined the effects of viewing a complementary public service announcement after an organ donation story in an episode of Grey's Anatomy. Results indicated that the public service announcement enhanced the beneficial impact of the story on viewers' discussion behavior (about one's organ donor wishes), discussion intention, and perceived learning. This experimental study is the first to examine the effects of viewing a non-character public service announcement after a health-related storyline in a developed nation's fictional program compared to viewing the same episode of the program on its own. It is important for future research to examine whether these findings replicate for different health issues and with a nationally representative sample.


Effect of hard gummy candy chewing on masticatory function.
Although various training methods have been reported for improving oral function such as occlusal force, there are few reports that show the training effect of eating hard food on the oral functions. To examine the training effects of habitually ating hard gummy candies on oral functions. Participants of this cohort study were recruited into a training (six women, eight men; mean age 27.6 ± 3.5 years) and control group (two women, seven men; mean age 28.3 ± 4.9 years). The training group ate nine custom-developed hard gummy candies three times per week for 3 months. Training effects were evaluated by measuring the maximal occlusal force, masticatory performance, maximal tongue pressure, number of chewing cycles until swallowing the candy, duration of chewing and cycle time before training, after 1, 2 and 3 months of training, and 1 month after stopping training. The iEMG/force, which evaluates masseter muscle hypertrophy with electromyograms (EMG), was calculated. Masticatory performance after 1 month (p = 0.01), maximal occlusal force after 2 months (p < 0.01) and maximal tongue pressure after 3 months of training were significantly increased (p = 0.02), and the cycle time after 2 months of training (p = 0.02) was significantly decreased compared to before the intervention. Except for masticatory performance, the other effects were maintained for 1 month after stopping training. Changes in iEMG/force were not significant, but a tendency for muscle hypertrophy was observed in the training group. Habitual eating of hard gummy candies is a task-specific training that can improve overall masticatory function, including tongue pressure.


Magnesium supplementation reduces inflammation in rats with induced chronic kidney disease.
Inflammation is a common feature in chronic kidney disease (CKD) that appears specifically associated with cardiovascular derangements in CKD patients. Observational studies have revealed a link between low Mg levels and inflammation. In this study, we hypothesize that Mg might have a modulatory effect on the inflammation induced under the uraemic milieu. In vivo studies were performed in a 5/6 nephrectomized rat model of CKD. Furthermore, a possible direct effect of Mg was addressed through in vitro studies with vascular smooth muscle cells (VSMCs). Uraemic rats fed a normal (0.1%) Mg diet showed a systemic inflammatory response evidenced by the elevation in plasma of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6, and GPx activity, a marker of oxidative stress. Importantly, an increased expression of these cytokines in the aortic tissue was also observed. In contrast, a dietary Mg supplementation (0.6%) greatly prevented the oxidative stress and the pro-inflammatory response. In vitro, in VSMCs cultured in a pro-inflammatory high phosphate medium, incubation with Mg 1.6 mM inhibited the increase in the production of ROS, the rise in the expression of TNF-α, IL-1β, IL-6 and IL-8 and the activation of NF-κB signalling that was observed in cells incubated with a normal (0.8 mM) Mg. Mg supplementation reduced inflammation associated with CKD, exerting a direct effect on vascular cells. These findings support a possible beneficial effect of Mg supplementation along the clinical management of CKD patients.


Nucleotide sequence of the lig gene and primary structure of DNA ligase of Escherichia coli.
The DNA ligase of Escherichia coli catalyses the NAD-dependent formation of phosphodiester linkages between 5'-phosphoryl and 3'-hydroxyl groups in DNA. It is essential for DNA replication and repair of damaged DNA strands. We determined the nucleotide sequence of the lig gene of Escherichia coli coding for DNA ligase and flanking regions. The coding frame of the gene was confirmed by the amino acid composition and the amino- and carboxyl-terminal amino acid sequences of the purified ligase. The ligase consists of 671 amino acid residues with a molecular weight of 73,690.


Endothelial biology in the post-menopausal obese woman.
Women generally have a reduced risk of cardiovascular disease (CVD). However, this protection of gender diminishes rapidly after menopause and with advancing age, particularly in obese women. Alterations in vascular function are thought to a key early step in the development of atherosclerosis. In this review, we will describe the features of endothelial dysfunction in the post-menopausal obese female and discuss the interplay of aging, estrogen withdrawal, and obesity. The objectives include (1) a review of endothelial biology and endothelial dysfunction, and (2) a discussion how the endothelial function is altered in the context of aging, hormonal changes and insulin resistance. The clinical consequences of endothelial dysfunction and CVD will also be reviewed.


Safely ruling out inflammatory bowel disease in children and teenagers without referral for endoscopy.
Up to 70% of children and teenagers referred to a paediatric gastroenterology centre with suspected inflammatory bowel disease (IBD) do not have the disease. To evaluate whether faecal calprotectin as an 'add-on test' improves the specificity of the clinical case definition for suspected IBD in a general paediatric practice. A prospective diagnostic accuracy study. Six outpatient clinics for general paediatrics and one tertiary care hospital in the Netherlands. 117 children and teenagers with a clinical suspicion of IBD. Faecal calprotectin was measured (index test) in all patients. Patients with a high index of suspicion on the basis of the paediatrician's global assessment, physical examination and blood results were referred for endoscopy (reference standard). Children and teenagers who were not selected for endoscopy initially were followed for half a year for the appearance of possible additional symptoms (delayed type reference standard). The proportion of referred patients with confirmed IBD. The mean age of patients was 14 years (range 6-18). A total of 42 (36%) had confirmed IBD. The paediatricians, who were blinded to the faecal calprotectin result, referred 68 children and teenagers for endoscopy. If they had referred only those patients with a positive faecal calprotectin result (>50 μg/g), 54 patients would have undergone endoscopy. The study relied on clinical follow-up to detect missed IBD. A diagnostic strategy in general paediatric practice of using a simple clinical case definition for suspected IBD in combination with a positive faecal calprotectin result increases the specificity to detect IBD and reduces the need for referral to a paediatric gastroenterology centre with a very low risk of missing cases.


Automatic prediction of tongue muscle activations using a finite element model.
Computational modeling has improved our understanding of how muscle forces are coordinated to generate movement in musculoskeletal systems. Muscular-hydrostat systems, such as the human tongue, involve very different biomechanics than musculoskeletal systems, and modeling efforts to date have been limited by the high computational complexity of representing continuum-mechanics. In this study, we developed a computationally efficient tracking-based algorithm for prediction of muscle activations during dynamic 3D finite element simulations. The formulation uses a local quadratic-programming problem at each simulation time-step to find a set of muscle activations that generated target deformations and movements in finite element muscular-hydrostat models. We applied the technique to a 3D finite element tongue model for protrusive and bending movements. Predicted muscle activations were consistent with experimental recordings of tongue strain and electromyography. Upward tongue bending was achieved by recruitment of the superior longitudinal sheath muscle, which is consistent with muscular-hydrostat theory. Lateral tongue bending, however, required recruitment of contralateral transverse and vertical muscles in addition to the ipsilateral margins of the superior longitudinal muscle, which is a new proposition for tongue muscle coordination. Our simulation framework provides a new computational tool for systematic analysis of muscle forces in continuum-mechanics models that is complementary to experimental data and shows promise for eliciting a deeper understanding of human tongue function.


Oncologic and Fertility Outcomes after Simple Trachelectomy in Women with Early Cervical Cancer.
This study aimed to present our case series of patients with early-stage cervical cancer undergoing simple trachelectomy (ST). Currently, radical trachelectomy is considered the most appropriate fertility-preserving procedure for the treatment of early-stage cervical cancer. However, there is increasing debate on the appropriate radicality of the surgery to preserve oncologic safety. Descriptive retrospective analysis of patient records and evaluation of questionnaires. 2 gynecologic oncologic centers, surgeries performed by one surgical team. 36 women with early-stage cervical cancer undergoing ST. Laparoscopic assisted simple vaginal trachelectomy. Demographic, histologic, fertility, and follow-up data of all patients who underwent ST between April 2007 and July 2021 were prospectively recorded and retrospectively analyzed. A total of 36 women (mean age: 28 years) underwent ST of whom 81% were nulliparous. Indications for ST were multifocal International Federation of Gynecology and Obstetrics stage IA1 (n = 30), stage IA1 L1 (n = 1), stage IA2 (n = 2), and stage IB1 (n = 3). Mandatory staging procedure was laparoscopic pelvic lymphadenectomy, including bilateral sentinel biopsy in 92% of the cases and systematic in 8%. Residual tumor was histologically confirmed in 8 specimens (22%); 18 women (50%) were seeking parenthood, and 13 succeeded (72%). There were 16 live births, all on term, with a median fetal weight of 3110 grams (2330-4420). One patient had a medical abortion owing to fetal congenital malformation. One pregnancy is ongoing. After a median follow-up of 91.5 months (9-174), all women are alive with no evidence of disease. ST represents a de-escalation compared with radical trachelectomy and provides excellent oncologic results with an outstanding fertility rate and obstetric outcome for patients with early cervical cancer. However, clear indications for this tailored fertility-preserving surgery have to be defined in well-designed trials.


Translation equations to compare ActiGraph GT3X and Actical accelerometers activity counts.
This study aimed to develop a translation equation to enable comparison between Actical and ActiGraph GT3X accelerometer counts recorded minute by minute. Five males and five females of variable height, weight, body mass index and age participated in this investigation. Participants simultaneously wore an Actical and an ActiGraph accelerometer for two days. Conversion algorithms and R(2) were calculated day by day for each subject between the omnidirectional Actical and three different ActiGraph (three-dimensional) outputs: 1) vertical direction, 2) combined vector, and 3) a custom vector. Three conversion algorithms suitable for minute/minute conversions were then calculated from the full data set. The vertical ActiGraph activity counts demonstrated the closest relationship with the Actical, with consistent moderate to strong conversions using the algorithm: y = 0.905x, in the day by day data (R(2) range: 0.514 to 0.989 and average: 0.822) and full data set (R(2) = 0.865). The Actical is most sensitive to accelerations in the vertical direction, and does not closely correlate with three-dimensional ActiGraph output. Minute by minute conversions between the Actical and ActiGraph vertical component can be confidently performed between data sets and might allow further synthesis of information between studies.


Visualization of replicating herpes simplex virus in cervical dorsal root ganglia of mice following explant of individual ganglion onto susceptible indicator cells.
Herpes simplex virus (HSV) establishes a latent state in the sensory ganglia of the peripheral nervous system of its natural or experimental host following primary infection. At various times thereafter, the virus can be reactivated from the latent state whereby it migrates back to the periphery and sometimes initiates a clinical syndrome referred to as recurrent disease. We inoculated mice in the right ear pinna and, following recovery from primary infection, killed the mice at various intervals following either the presence or absence of peripheral stimulations. Explanted cervical dorsal root ganglia yielded HSV in culture and was positive for HSV-like virus particles when viewed with the electron microscope. Hematoxylin and eosin staining showed neuron degeneration, and corresponding HSV-specific immunoperoxidase stains were also positive. The data indicate that ganglionic cells are capable of supporting replicating HSV and that, in vitro, numerous ganglionic cells can be infected simultaneously.


Learning to estimate the fiber orientation distribution function from diffusion-weighted MRI.
Estimation of white matter fiber orientation distribution function (fODF) is the essential first step for reliable brain tractography and connectivity analysis. Most of the existing fODF estimation methods rely on sub-optimal physical models of the diffusion signal or mathematical simplifications, which can impact the estimation accuracy. In this paper, we propose a data-driven method that avoids some of these pitfalls. Our proposed method is based on a multilayer perceptron that learns to map the diffusion-weighted measurements, interpolated onto a fixed spherical grid in the q space, to the target fODF. Importantly, we also propose methods for synthesizing reliable simulated training data. We show that the model can be effectively trained with simulated or real training data. Our phantom experiments show that the proposed method results in more accurate fODF estimation and tractography than several competing methods including the multi-tensor model, Bayesian estimation, spherical deconvolution, and two other machine learning techniques. On real data, we compare our method with other techniques in terms of accuracy of estimating the ground-truth fODF. The results show that our method is more accurate than other methods, and that it performs better than the competing methods when applied to under-sampled diffusion measurements. We also compare our method with the Sparse Fascicle Model in terms of expert ratings of the accuracy of reconstruction of several commissural, projection, association, and cerebellar tracts. The results show that the tracts reconstructed with the proposed method are rated significantly higher by three independent experts. Our study demonstrates the potential of data-driven methods for improving the accuracy and robustness of fODF estimation.


The influence of student interest on teaching evaluation.
To analyze the influence of student subject bias on the evaluation of didactic teaching. Prospective study evaluating the relationship between the interest of junior students in 30 clinical topics and the students' subsequent evaluations of lecturers for these topics. University internal medicine junior core curriculum. 56 junior students. Lecturers were senior internal medicine residents. None. There was no correlation between mean student interest scores for the topics and either immediate or end-of-rotation lecturer evaluation scores (R = -0.14 and 0.09 and p = 0.47 and 0.61, respectively). For 20 of 30 topics (66%) more than 50% of the students assigned the same level of high, intermediate, or low interest. There was no significant difference (p = 0.84) in the mean lecturer evaluation scores for these three divergent groups. Analysis of individual lecturers' evaluation scores revealed stratification to a given range independent of student interest in the topic. Students do not appear to be biased by their degree of interest in a subject when evaluating teaching skills. It appears unlikely that specific teaching assignments need to be considered when evaluating competence in didactic teaching.


Physiological gas exchange in the middle ear cavity.
Many reports pointed out that gas exchange in and out of the middle ear cavity occurs not only via the Eustachian tube but also across the middle ear mucosa. Our earlier study on children with otitis media with effusion (OME) for which a tympanic ventilation tube (TUBE) had been inserted revealed that the more severe the inflammatory change of the middle ear mucosa, the higher the degree of impairment of the transmucosal gas exchange function and the greater the decrease in the middle ear total pressure (METP). We hypothesized that the change in METP is caused by gas migration, and we conducted the present animal study to test this hypothesis and to determine the importance of METP measurement. Using 30 rabbits, ten in a group in which the middle ear cavity gas was replaced with atmospheric air (Group 1, oxygen (O(2)) 20%, carbon dioxide (CO(2)) 0.03% and nitrogen (N(2)) 79.9%), ten in a group replaced with a high CO(2) pressure gas whose partial pressure of CO(2) only was increased to 5% (Group 2, O(2) 20%, CO(2) 5% and balanced with N(2)) and ten in a group replaced with a low O(2) pressure gas (Group 3, O(2) 5%, CO(2) 0.03% and balanced with N(2)), changes in the METP were measured. Group 1 showed a pressure change (increase, peak and then decrease in the METP) similar to that observed in a clinical cured group of OME with TUBE. In Group 2, no increase in the METP was observed and in Group 3 increase in the METP was observed but no decrease in the METP was observed. It was found that the increase in the METP is attributable to diffusion of CO(2). This study elucidated that the change in the METP is a physiological response. Since the METP correlates with the degree of histologic inflammatory change in the middle ear mucosa, which was revealed in our clinical study of OME, it was reconfirmed that measurement of the METP is an important test method for evaluation of the degree of improvement in the pneumatic cavity mucosa.


Job strain, life events, and sickness absence: a longitudinal cohort study in a random population sample.
To examine job strain, adverse life events, and their co-occurrence as predictors of sickness absence. Random sample-based mail survey data on 1806 Finns in gainful employment were linked to sickness absence records (1987-1998) from national health registers. Generalized linear models with negative binomial distribution assumption were applied. After adjustment for demographic characteristics and health behavior, job strain (rate ratio [RR] 1.73; 95% confidence interval [CI] = 1.21-2.48), but not life events, independently predicted increased rate of sickness absence among men. The opposite was true for women, (RR for life events 1.39; 95% CI = 1.10-1.75). No statistically significant interaction between job strain and life events was detected. In addition to job strain, strain originating in private life should be kept in mind when the need for sickness absence of women employees is evaluated within health care.


Determination of potentially toxic metals in depilatory products in the Iranian markets: human health risk assessment.
This study aimed to investigate the concentrations of heavy metals, including lead (Pb), cadmium (Cd), chromium (Cr), zinc (Zn), cobalt (Co), and arsenic metalloid (As), to assess their health risks in the popular depilatory products of the Iranian markets. Twenty-one samples of 7 popular brands of depilatory products, inclusive of cream and powder, were examined. Selected elements were measured by inductively coupled plasma optical emission spectrometry (ICP-OES) using the appropriate procedure for acid digestion and the measurement of heavy metal contents. The differences in heavy metal concentrations were investigated according to the type of product, brand, country of production, and product price using t test and one-way analysis of variance and post hoc Tukey test. Finally, carcinogenic and non-carcinogenic risk assessments were calculated for the studied elements. The results showed that Pb (5.46±2.30 mg/kg) and Co (0.16±0.69 mg/kg) had the highest and lowest concentrations in these products, respectively. In general, the concentration of heavy metals in depilatory creams was less than the concentration of elements in depilatory powders and less than the maximum allowable limits as defined by the Institute of Standards and Industrial Research of Iran (ISIRI). There was a direct and significant relationship between the concentration of heavy metals in depilatory powders and the product's price. Moreover, the amount of As in one of the brands of depilatory powder was determined to exceed the standard value (2 mg/kg). Also, hazard index (HI) and lifetime cancer risk (LCR) were below 1 and 10-6, respectively, which indicated that this mentioned heavy metal had no probable non-carcinogenic and carcinogenic risks for consumers. According to this study, it was evident that the chances of cancer and non-cancer risk using depilatory products were unlikely, but continuous use can be harmful due to the excessive accumulation of these heavy metals.


Differential effects of a Rab6 mutant on secretory versus amyloidogenic processing of Alzheimer's beta-amyloid precursor protein.
The Ras-related GTP-binding protein, Rab6, is localized in late Golgi compartments where it mediates intra-Golgi vesicular trafficking. Herein we report that coexpression of Alzheimer's beta-amyloid precursor protein (beta APP751) with a dominant-negative Rab6 mutant (Rab6N126I) in human embryonal kidney 293 cells causes an increase in secretion of the soluble amino-terminal exodomain (s-APP alpha) derived from non-amyloidogenic processing of beta-APP751 by alpha-secretase. The effect was specific to Rab6N126I, since the corresponding mutation in Rab8 (i.e. Rab8N121I), which has been implicated in protein transport to the plasma membrane, caused a modest reduction in s-APP alpha secretion. While Rab6N126I stimulated secretion of APP alpha, the accumulation of amyloid beta peptide (A beta) in the medium was either moderately reduced or unaffected. Similar differential effects of Rab6N126I on secretion of s-APP alpha versus A beta were observed in cell cultures that were overproducing A beta after transfection with a plasmid encoding Swedish variant of beta APP751. Moreover, assays of medium from the latter cultures revealed a marked increase in secretion of s-APP alpha relative to s-APP beta (the immediate product derived from cleavage of beta APP by beta-secretase). The results indicate that vesicular transport events controlled by Rab6 occur at or near a critical juncture in the trans-Golgi network where beta APP is sorted into either the constitutive alpha-secretase pathway or the amyloidogenic beta-secretase pathway.


Persistent back pain--why do physical therapy clinicians continue treatment? A mixed methods study of chiropractors, osteopaths and physiotherapists.
(a) To investigate how widespread is the use of long term treatment without improvement amongst clinicians treating individuals with low back pain. (b) To study the beliefs behind the reasons why chiropractors, osteopaths and physiotherapists continue to treat people whose low back pain appears not to be improving. A mixed methods study, including a questionnaire survey and qualitative analysis of semi-structured interviews. Questionnaire survey; 354/600 (59%) clinicians equally distributed between chiropractic, osteopathy and physiotherapy professions. Interview study; a purposive sample of fourteen clinicians from each profession identified from the survey responses. Methodological techniques ranged from grounded theory analysis to sorting of categories by both the research team and the subjects themselves. At least 10% of each of the professions reported that they continued to treat patients with low back pain who showed almost no improvement for over three months. There is some indication that this is an underestimate. reasons for continuing unsuccessful management of low back pain were not found to be primarily monetary in nature; rather it appears to have much more to do with the scope of care that extends beyond issues addressed in the current physical therapy guidelines. The interview data showed that clinicians viewed their role as including health education and counselling rather than a 'cure or refer' approach. Additionally, participants raised concerns that discharging patients from their care meant sending them to into a therapeutic void. Long-term treatment of patients with low back pain without objective signs of improvement is an established practice in a minority of clinicians studied. This approach contrasts with clinical guidelines that encourage self-management, reassurance, re-activation, and involvement of multidisciplinary teams for patients who do not recover. Some of the rationale provided makes a strong case for ongoing contact. However, the practice is also maintained through poor communication with other professions and mistrust of the healthcare system.


Corneal higher-order aberrations in corneal endothelial decompensation secondary to obstetric forceps injury.
Forceps corneal injuries during infant delivery cause Descemet membrane (DM) breaks, that cause corneal astigmatism and corneal endothelial decompensation. The aim of this study is to characterise corneal higher-order aberrations (HOAs) and corneal topographic patterns in corneal endothelial decompensation due to obstetric forceps injury. This retrospective study included 23 eyes of 21 patients (54.0 ± 9.0 years old) with forceps corneal injury, and 18 healthy controls. HOAs and coma aberrations were significantly larger in forceps injury (1.05 [0.76-1.98] μm, and 0.83 [0.58-1.69], respectively) than in healthy controls (0.10 [0.08-0.11], and 0.06 [0.05-0.07], respectively, both P < 0.0001). Patient visual acuity was positively correlated with coma aberration (rs = 0.482, P = 0.023). The most common topographic patterns were those of protrusion and regular astigmatism (both, six eyes, 26.1%), followed by asymmetric (five eyes, 21.7%), and flattening (four eyes, 17.4%). These results indicate that increased corneal HOAs are associated with decreased visual acuity in corneal endothelial decompensation with DM breaks and corneal topography exhibits various patterns in forceps injury.