Treatment of patients with Graves' disease and the appropriate extent of thyroidectomy.
Graves' disease is an autoimmune disorder caused by thyroid stimulating auto-antibodies directed against the thyrotropin receptor on thyroid follicular cells. It is the most common cause of hyperthyroidism and is associated with cardiovascular, ophthalmologic and other systemic manifestations. Three treatment options are available for Graves' disease: anti-thyroid drugs, radioactive iodine and thyroidectomy. While thyroidectomy is the least common option used for treatment of Graves' disease, it is preferentially indicated for patients with a large goiter causing compressive symptoms, suspicious or malignant thyroid nodules or significant ophthalmopathy. The best operation for Graves' disease has been a matter of debate. The standard operation was a subtotal thyroidectomy for much of the twentieth century, however, over the past 20 years total thyroidectomy has been increasingly performed. Herein, we provide a historical perspective and review the current literature, including randomized controlled trials, systematic reviews and meta-analyses and conclude that total thyroidectomy is the preferred option for the surgical treatment of Graves' disease, with a nearly 0% recurrence rate, predictable postoperative hypothyroidism and a low complication rate comparable to subtotal thyroidectomy when performed by high-volume thyroid surgeons.


Seasonal variations in haematological and biochemical parameters.
Biochemical and haematological data obtained over five consecutive years are presented on the male workforce of a large chemical company. The data have been subjected to statistical analysis and quantify the influence of age and the month of the year in which the samples were taken. The red cell count, white cell count, serum gamma-glutamyl transferase, alanine transaminase and creatinine show significant and consistent seasonal variations. The previously published work on the influence of age on several indices is confirmed. Biochemical screening may be a method of detecting early signs of toxicity in man but such factors as age, sex and season must be taken into account when comparing the results obtained from exposed and non-exposed groups.


Enhanced bioelectricity output of microbial fuel cells via electrospinning zeolitic imidazolate framework-67/polyacrylonitrile carbon nanofiber cathode.
In this study, the zeolitic imidazolate framework-67 (ZIF-67) and electrospinning polyacrylonitrile membrane were combined to prepare electrospinning carbon nanofibers composite cathode (ZIF-67/CNFs) which could enhance the oxygen reduction reaction (ORR) performance of microbial fuel cells (MFCs) cathode. The optimum electrode 3 wt% ZIF-67/CNFs revealed the excellent ORR performance with a half-wave potential of -0.03 V vs. Ag/AgCl, which was more positive than Pt/C-CC (-0.09 V vs. Ag/AgCl). The highest output voltage (607±9 mV) and maximum power density (1.191±0.017 W m-2) were obtained when the prepared ZIF-67/CNFs electrode was applied to the cathode of MFC (ZIF-67/CNFs-MFC). In addition, ZIF-67/CNFs-MFC showed the best pollutant removal effect. Geobacter was the highest proportion of microbial in ZIF-67/CNFs-MFC. The results have shown that the application of ZIF-67/CNFs electrode to MFC cathode is promising.


Impaired plantar sensitivity among the obese is associated with increased postural sway.
Impaired foot plantar sensitivity has been hypothesized among individuals who are obese, and may contribute to their impaired balanced during quiet standing. The objective of this study was to investigate the effects of obesity on plantar sensitivity, and explore the relationship between plantar sensitivity and balance during quiet standing. Thirty-nine young adults from the university population participated in the study including 19 obese and 20 non-obese adults. Plantar sensitivity was measured as the force threshold at which an increasing force applied to the plantar surface of the foot was first perceived, and the force threshold at which a decreasing force was last perceived. Measurements were obtained while standing, and at two locations on the plantar surface of the dominant foot. Postural sway during quiet standing was then measured under three different sensory conditions. Results indicated less sensitive plantar sensitivity and increased postural sway among the obese, and statistically significant correlations between plantar sensitivity and postural sway that were characterized as weak to moderate in strength. As such, impaired plantar sensitivity among individuals who are obese may be a mechanism by which obesity degrades standing balance among these individuals.


Renal clearances of estriol conjugates in normal human pregnancy at term.
In late human pregnancy more than 90 per cent of the total estriol (E3) in body fluids consists of four conjugates, estriol-3-sulfate (E3-3S), estriol-16-glucosiduronate (E3-16G), estriol-3-glucuronide (E3-3G), and estriol-3-sulfate-16-glucosiduronate (E3-3S-16G). Since the relative amounts of E3 in blood and urine would be determined by the kidney, the renal clearance of each conjugate was determined and compared with inulin and p-aminohippuric acid (PAH) clearance, as measures of glomerular filtration rate (GFR) and the effective renal plasma flow. Five women were studied in the lateral decubitus position with inulin and PAH infusion. Samples of blood and urine were collected at 40 minute intervals and analyzed. The method for E3 conjugates involved separation of the four conjugates on Sephadex LH-20, enzyme hydrolysis, and radioimmunoassay. Renal clearances for E3-3S and E3-3S-16G were below inulin. E3-3G approximated inulin; E3-16G exceeded inulin and approached PAH. In plasma E3-3S-16G represented 48.4 +/- 7.2 per cent; in urine E3-16G represented 69.5 +/- 7.3 per cent of total E3. Thus, different conjugates predominate in blood and urine.


Lipid droplets and the transcriptome of Mycobacterium tuberculosis from direct sputa: a literature review.
Mycobacterium tuberculosis (Mtb), the main etiology of tuberculosis (TB), is predominantly an intracellular pathogen that has caused infection, disease and death in humans for centuries. Lipid droplets (LDs) are dynamic intracellular organelles that are found across the evolutionary tree of life. This review is an evaluation of the current state of knowledge regarding Mtb-LD formation and associated Mtb transcriptome directly from sputa.Based on the LD content, Mtb in sputum may be classified into three groups: LD positive, LD negative and LD borderline. However, the clinical and evolutionary importance of each state is not well elaborated. Mounting evidence supports the view that the presence of LD positive Mtb bacilli in sputum is a biomarker of slow growth, low energy state, towards lipid degradation, and drug tolerance. In Mtb, LD may serve as a source of chemical energy, scavenger of toxic compounds, prevent destruction of Mtb through autophagy, delay trafficking of lysosomes towards the phagosome, and contribute to Mtb persistence. It is suggest that LD is a key player in the induction of a spectrum of phenotypic and metabolic states of Mtb in the macrophage, granuloma and extracellular sputum microenvironment. Tuberculosis patients with high proportion of LD positive Mtb in pretreatment sputum was associated with higher rate of poor treatment outcome, indicating that LD may have a clinical application in predicting treatment outcome.The propensity for LD formation among Mtb lineages is largely unknown. The role of LD on Mtb transmission and disease phenotype (pulmonary TB vs extra-pulmonary TB) is not well understood. Thus, further studies are needed to understand the relationships between LD positivity and Mtb lineage, Mtb transmission and clinical types.


Scleral necrosis after brachytherapy for uveal melanoma: Analysis of risk factors.
Radiation-induced scleral necrosis (RISN) is a rare, but a serious complication of brachytherapy for uveal melanoma. We aimed at analysing the incidence, timing and risk factors associated with development of RISN in a large institutional series. All consecutive cases with brachytherapy for uveal melanoma treated by the Departments of Ophthalmology and Radiotherapy at University Hospital Essen between 1999 and 2016 were eligible. Development of RISN during the post-treatment follow-up was recorded. A 1:2 propensity score matched case-control study was performed for the evaluation of the prognostic value of different tumour- and treatment-associated parameters. RISN was documented in 115 (2.9%) of 3960 patients with uveal melanoma included in the final analysis, and occurred at the mean 30.3 months (range: 1.26-226 months) after brachytherapy. In the whole cohort, younger age (p = 0.042), plaque type (p = 0.001) and ciliary body involvement (p < 0.0001) were independently associated with the RISN occurrence. In the case-control study, multivariable weighted proportional hazard analysis discovered the association of the following additional tumour- and treatment-associated characteristics with RISN: posterior tumour margin anterior to equatorial region (p = 0.0003), extraocular tumour extension (p = <0.0001), scleral contact dose (p = <0.0001), conjunctival dehiscence after therapy (p = 0.0001), disinsertion of the superior rectus muscle (p = 0.001) and the glaucoma medication (p = 0.014). Our study confirms RISN as a rare complication, which might occur even years later after the brachytherapy for uveal melanoma. Alongside with scleral dose five other tumour and therapy related factors predict the risk of RISN after brachytherapy for uveal melanoma were established.


Abnormal glomerular and tubular function during angiotensin converting enzyme inhibition in renovascular hypertension evaluated by the lithium clearance method.
Glomerular filtration rate (GFR) and tubular function were measured by means of the lithium clearance technique in 14 patients with renovascular hypertension (RVH) and eight patients with essential hypertension (EH) before and after oral administration of captopril 25 mg. In RVH captopril reduced 51-Cr-EDTA clearance (67.3 (median) to 47.5 ml min-1, P less than 0.01), proximal absolute reabsorption of fluid (53.9 to 41.5 ml min-1, P less than 0.01) and distal absolute reabsorption of sodium (2195 to 1402 mumol min-1, P less than 0.01), whereas proximal fractional reabsorption increased slightly (77.5 to 80.2%, P less than 0.02). In EH, however, these parameters were practically unaffected by captopril. In both RVH and EH plasma concentrations of angiotensin II and aldosterone were reduced after captopril, but atrial natriuretic peptide in plasma and urinary excretion rate of prostaglandin E2 were unchanged. Blood pressure decreased after captopril in both groups, but the maximum fall in systolic BP was more pronounced in RVH (22%) than EH (13%). It is concluded that angiotensin converting enzyme inhibition markedly reduced absolute reabsorption in both the proximal and distal tubules in RVH, in contrast to EH, predominantly due to fall in the GFR, and that the slight increase in proximal fractional reabsorption may be attributed to a reduction in the hydrostatic pressure in the peritubular vessels.


Peptide dendrimer-conjugates of ketoprofen: Synthesis and ex vivo and in vivo evaluations of passive diffusion, sonophoresis and iontophoresis for skin delivery.
The aim of this study was to evaluate skin delivery of ketoprofen when covalently tethered to mildly cationic (2+ or 4+) peptide dendrimers prepared wholly by solid phase peptide synthesis. The amino acids glycine, arginine and lysine formed the dendrimer with ketoprofen tethered either to the lysine side-arm (Nε) or periphery of dendrimeric branches. Passive diffusion, sonophoresis- and iontophoresis-assisted permeation of each peptide dendrimer-drug conjugate (D1-D4) was studied across mouse skin, both in vitro and in vivo. In addition, skin toxicity of dendrimeric conjugates when trialed with iontophoresis or sonophoresis was also evaluated. All dendrimeric conjugates improved aqueous solubility at least 5-fold, compared to ketoprofen alone, while also exhibiting appreciable lipophilicity. In vitro passive diffusion studies revealed that ketoprofen in its native form was delivered to a greater extent, compared with a dendrimer-conjugated form at the end of 24h (Q24h (μg/cm2): ketoprofen (68.06±3.62)>D2 (49.62±2.92)>D4 (19.20±0.89)>D1 (6.45±0.40)>D3 (2.21±0.19). However, sonophoresis substantially increased the skin permeation of ketoprofen-dendrimer conjugates in 30min (Q30min (μg/cm2): D4 (122.19±7.14)>D2 (66.74±3.86)>D1 (52.10±3.22)>D3 (41.66±3.22)) although ketoprofen alone again proved superior (Q30min: 167.99±9.11μg/cm2). Next, application of iontophoresis was trialed and shown to considerably increase permeation of dendrimeric ketoprofen in 6h (Q6h (μg/cm2): D2 (711.49±39.14)>D4 (341.23±16.43)>D3 (89.50±4.99)>D1 (50.91±2.98), with a Q6h value of 96.60±5.12μg/cm2 for ketoprofen alone). In vivo studies indicated that therapeutically relevant concentrations of ketoprofen could be delivered transdermally when iontophoresis was paired with D2 (985.49±43.25ng/mL). Further, histopathological analysis showed that the dendrimeric approach was a safe mode as ketoprofen alone. The present study successfully demonstrates that peptide dendrimer conjugates of ketoprofen, when combined with non-invasive modalities, such as iontophoresis can enhance skin permeation with clinically relevant concentrations achieved transdermally.


Synthesis and SAR of highly potent and selective dopamine D(3)-receptor antagonists: 1H-pyrimidin-2-one derivatives.
The synthesis and SAR of novel highly potent and selective dopamine D(3)-receptor antagonists based on a 1H-pyrimidin-2-one scaffold are described. A-690344 antagonized PD 128907-induced huddling deficits in rat (ED(50) 6.1mg/kg po), a social interaction paradigm.


Inverse Design of Tetracene Polymorphs with Enhanced Singlet Fission Performance by Property-Based Genetic Algorithm Optimization.
The efficiency of solar cells may be improved by using singlet fission (SF), in which one singlet exciton splits into two triplet excitons. SF occurs in molecular crystals. A molecule may crystallize in more than one form, a phenomenon known as polymorphism. Crystal structure may affect SF performance. In the common form of tetracene, SF is experimentally known to be slightly endoergic. A second, metastable polymorph of tetracene has been found to exhibit better SF performance. Here, we conduct inverse design of the crystal packing of tetracene using a genetic algorithm (GA) with a fitness function tailored to simultaneously optimize the SF rate and the lattice energy. The property-based GA successfully generates more structures predicted to have higher SF rates and provides insight into packing motifs associated with improved SF performance. We find a putative polymorph predicted to have superior SF performance to the two forms of tetracene, whose structures have been determined experimentally. The putative structure has a lattice energy within 1.5 kJ/mol of the most stable common form of tetracene.


The feasibility of a Paleolithic diet for low-income consumers.
Many low-income consumers face a limited budget for food purchases. The United States Department of Agriculture developed the Thrifty Food Plan to address this problem of consuming a healthy diet given a budget constraint. This dietary optimization program uses common food choices to build a suitable diet. In this article, the United States Department of Agriculture data sets are used to test the feasibility of consuming a Paleolithic diet given a limited budget. The Paleolithic diet is described as the diet that humans are genetically adapted to, containing only the preagricultural food groups of meat, seafood, fruits, vegetables, and nuts. Constraints were applied to the diet optimization model to restrict grains, dairy, and certain other food categories. Constraints were also applied for macronutrients, micronutrients, and long-chain polyunsaturated fatty acids. The results show that it is possible to consume a Paleolithic diet given the constraints. However, the diet does fall short of meeting the daily recommended intakes for certain micronutrients. A 9.3% increase in income is needed to consume a Paleolithic diet that meets all daily recommended intakes except for calcium.


Educational guidance for functional visual diversity in Nicaragua. Design and evaluation of a teacher-training program.
The article exposes the process of design and implementation of a training program for teachers that teach people with Visual Functional Diversity (VFD), taking into account their needs both in training and in the provision of resources in Nicaragua. To verify the effectiveness of the program, a quasi-experimental design was carried out with a non-equivalent pretest and posttest control group. The experimental group received training while the control group did not receive training. The evaluation of the results obtained after the application of the program was carried out through two instruments: an efficacy questionnaire and a satisfaction questionnaire. The results showed significant differences between the experimental and control group after the application of the program (Z = -4,383; p = 0.000) in favor of the experimental group. It is confirmed that the program is effective in training teachers on inclusive education for the visually impaired as the teachers who took part in the training program significantly increased their knowledge in that issue.


Carbonic anhydrase activity in the trigeminal primary afferent neuronal cell bodies with peripheral axons innervating the mandibular molar tooth pulps of the rat.
Trigeminal primary afferent neuronal cell bodies were labeled with FITC-WGA retrogradely transported from the mandibular molar tooth pulp (tooth pulp) and the cutaneous branch of the mylohyoid nerve (cutaneous nerve) in the rat. Tissue sections were then incubated in Hansson's medium for histological demonstration of carbonic anhydrase (CA) activity. About 85% of primary neurons innervating the tooth pulp had medium to large cell bodies (greater than or equal to 300 microns 2 in cross-sectional area), while 77% of those innervating the cutaneous nerve were small (less than 300 microns 2). A total of 32% of the tooth pulp cells exhibited CA activity. CA-containing cells constituted only about 4% of the cutaneous nerve cells. In view of the known distribution of CA within the rodent nervous system, the CA-containing cells are considered to represent the tooth pulp primaries conducting in A-beta velocity range and projecting to rostral subdivisions of the brainstem sensory trigeminal nuclear complex.


Experiences of relocation in dementia care from the perspective of six care workers.
Relocation of persons with dementia might be considered when quality of care cannot be sustained due to increasing needs. Relocation has been studied from the aspects of mortality and morbidity. AIM. To explore the thoughts and experiences of care workers when relocating a person with dementia within municipal sheltered housing. This qualitative study was conducted in Sweden and based on interviews with six care workers involved in the relocation of two persons with dementia. Latent content analysis was applied. The findings of one narrative are summarised in the theme 'Walking the tightrope: trying to balance conflicting needs'. In the other narrative the theme 'Balancing closeness and distance' emerged. Eight sub-themes were identified illustrating the relocation time-line. Relocation from the care workers' perspective is a complex process with conflicting values and practical issues that hinder the provision of good care and security. Supporting next of kin in the relocation decision-making process presupposes time for reflection in dialogue with staff. The risk of moral distress should be observed and support for care workers could be provided in the form of supervision, ethical consultations and local guidelines.


Possible involvement of Rab11 p24, a Ras-like small GTP-binding protein, in intracellular vesicular transport of isolated pancreatic acini.
Rab11 p24 is a Ras-like small guanosine triphosphate (GTP)-binding protein, and specific antibodies against it were newly developed to explore its function. Using the antibody, Rab11 p24 was shown to be abundant in rat pancreas as well as in most rat tissues. To explore the involvement of Rab11 p24 into the exocytotic process, the subcellular distribution of Rab11 p24 in rat pancreatic acini was evaluated also by use of the antibody. When the isolated acini were incubated with 1 x 10(-10) M cholecystokinin octapeptide (CCK-8) that induced the maximal stimulation, the amount of Rab11 p24 increased in the fractions of plasma membrane and zymogen granules, but decreased in the cytosol fraction. This redistribution was time-dependent and occurred within 1 min after the CCK-8 stimulation and reached a maximal level within 2 min after the stimulation. Moreover, a light microscopic immunolabeling technique on the isolated rat pancreatic acini also revealed that higher immunoreactivity with Rab11 p24 was observed over the zymogen granule membrane under CCK-8 stimulation. The present results indicate that Rab11 p24 is translocated from cytosol to the membrane fraction during stimulation with CCK-8 and suggest that Rab11 p24 is involved in the intracellular vesicular transport of isolated acini.


Epistaxis grading in Osler's disease: comparison of comprehensive scores with detailed bleeding diaries.
Use of reliable grading scores to measure epistaxis severity in hereditary hemorrhagic telangiectasia (HHT) is essential in clinical routine and for scientific purposes. For practical reasons, visual analog scale (VAS) scoring and the Epistaxis Severity Score (ESS) are widely used. VAS scores are purely subjective, and a potential shortcoming of the ESS is that it is based on self-reported anamnestic bleeding data. The aim of this study was to validate the level of correlation between VAS scores, the ESS, and actual bleeding events, based on detailed epistaxis diaries of patients. Records from daily epistaxis diaries maintained by 16 HHT patients over 112 consecutive days were compared with the monthly ESS and daily VAS scores in the corresponding time period. The Spearman rank correlation coefficient, analysis of variance models, and multiple R2 measures were used for statistical analysis. Although the ESS and VAS scores generally showed a high degree of correlation with actual bleeding events, mild events were underrepresented in both scores. Our results highlight the usefulness of the ESS as a standard epistaxis score in cohorts with moderate to severe degrees of epistaxis. The use of detailed epistaxis diaries should be considered when monitoring patients and cohorts with mild forms of HHT.


Influence of hail suppression systems over silver content in the environment in Aragón (Spain). II: Water, sediments and biota.
The silver content in soils in the area in the surroundings of the Gallocanta Lake (Aragón, NE Spain) is lower than expected considering the estimated silver emission during the last 50 years by hail suppression systems. To understand the silver accumulation processes, selected water (4 surface, 3 groundwater), biota and sediment (6 surface sediments and 3 cores from Gallocanta and Campillo de Dueñas Lakes and Used Reservoir) samples have been analysed. An essay comparing the growth of wheat in pots with different silver iodide concentrations has been carried out. Finally, silver content in 7 tissues from two sheep that graze in areas both with and without hail suppression systems during 6-8 years were analysed. Our results show that after 50 years of silver iodide emissions to the atmosphere, silver accumulation in the waters and sediments of the lowlands, including some wetlands of high ecological value, has not been significant. Sediment cores did not show any peaks associated to silver emission. We propose that constant absorption of silver by plants could explain the low concentration in water and sediments. Crops and grass could accumulate the excess silver, as both wheat and sheep are able to absorb significant amounts of silver. These bio - accumulation processes could have helped to avoid a progressive environmental deterioration of the surroundings of the Gallocanta Lake. However, this hypothesis should be corroborated and quantified by further research on the analysis of natural and agricultural areas under the influence of hail suppression systems.


Validation of the Simplified Motor Score in the out-of-hospital setting for the prediction of outcomes after traumatic brain injury.
The Glasgow Coma Scale (GCS) score is widely used to assess patients with head injury but has been criticized for its complexity and poor interrater reliability. A 3-point Simplified Motor Score (SMS) (defined as obeys commands=2, localizes pain=1, and withdraws to pain or worse=0) was created to address these limitations. Our goal is to validate the SMS in the out-of-hospital setting, with the hypothesis that it is equivalent to the GCS score for discriminating brain injury outcomes. This was a secondary analysis of an urban Level I trauma registry. Four outcomes and their composite were studied: emergency tracheal intubation, clinically meaningful brain injury, need for neurosurgical intervention, and mortality. The out-of-hospital GCS score and SMS were evaluated by comparing areas under the receiver operating characteristic curve with a paired nonparametric approach. Multiple imputation was used for missing data. A clinically significant difference in areas under the receiver operating characteristic curve was defined as greater than or equal to 0.05, according to previous literature. We included 19,408 patients, of whom 18% were tracheally intubated, 18% had brain injuries, 8% required neurosurgical intervention, and 6% died. The difference between the area under the receiver operating characteristic curve for the out-of-hospital GCS score and SMS was 0.05 (95% confidence interval [CI] -0.01 to 0.11) for emergency tracheal intubation, 0.05 (95% CI 0 to 0.09) for brain injury, 0.04 (95% CI -0.01 to 0.09) for neurosurgical intervention, 0.08 (95% CI 0.02 to 0.15) for mortality, and 0.05 (95% CI 0 to 0.10) for the composite outcome. In this external validation, SMS was similar to the GCS score for predicting outcomes in traumatic brain injury in the out-of-hospital setting.


Effects of physical activity on bone remodeling.
Physical exercise is recommended to improve bone mass in growing children and decrease bone loss in elderly men and women. However, the specific mechanisms by which exercise influences bone metabolism are still not thoroughly understood. The effect of physical activity on the skeleton is generally evaluated by dual-energy x-ray absorptiometry, which measures bone mineral density. However, a relatively long period is needed to detect even a minor variation in bone mineral density with this technique, limiting its usefulness. Bone biochemical markers that reflect the cellular activities of bone formation and resorption are thus also useful tools, both to monitor the acute effects of exercise on bone remodeling and to investigate the mechanisms of exercise-induced changes in bone mass. This article describes the effects of physical activity on bone remodeling in various types of population. The comparison of sedentary individuals and athletes with many years of high-volume sports practice, for example, has clarified some of the long-term effects of exercise. Moreover, the acute variation in bone cell activities after brief exercise or a training program is here examined. The interpretation of results is difficult, however, because of the many parameters, such as age, that are involved. The various populations are therefore categorized to reflect the biological factors implicated in the modulation of bone marker response during exercise.


Facial rhytidectomy approach for treatment of posterior mandibular fractures.
Surgical access to fractures of the ascending ramus of the mandible is limited when standard techniques are employed. A new method using a facial rhytidectomy technique is described, and seven cases treated by this method are presented. The advantage of this technique includes excellent exposure, predictable and safe dissection, inconspicuous facial scar and minimal postoperative complications.


Strange old worlds: socio-critical reports about old-age experiences in West German print media (1970s-1990s).
This article examines West German images of old age and the elderly in a period when this increasingly became a topical issue. Between the 1970s and the 1990s, the elderly were the subject of socio-critical reports in leading political magazines like Der Spiegel, Die Zeit and Stern. In these specific journalistic formats, the media entered unfamiliar places like old people's homes, the elderly's private apartments or tea dances for senior citizens. By analysing the language used in such media reports, this article shows continuity and change in attitudes towards the elderly, explores the impact of the new old-age model 'the young at heart', and the relevance of gender and generational ascriptions. In doing so, this article uncovers the recent historical context of current social debates about old age.


Lower social participation partly explains the association between perceived neighbourhood crime and depressive symptoms in European adults aged 50 years or older: A longitudinal mediation analysis.
Neighbourhood crime likely increases the risk of developing depression among older adults. However, little is known about the underlying behavioural and social pathways. We examined the association between perceived neighbourhood crime and depressive symptoms and whether this relationship was mediated by health behaviours (physical activity, smoking, and alcohol consumption) and social participation. Furthermore, we explored differential vulnerability across age, gender, education and household wealth. Data were drawn from six waves of longitudinal data (from 2004/2005 to 2017) of approximately 15,000 adults aged 50 years and older, derived from the multi-national Survey of Health, Ageing and Retirement in Europe. Perceived neighbourhood crime and covariates were measured at baseline, time-variant mediators and depressive symptoms across all waves. Confounder-adjusted mediator and outcome models were fitted with mixed-effects models. Total association was decomposed into direct and indirect pathways applying causal mediation analyses with Monte-Carlo simulations. Perceived crime was associated with higher risk of depressive symptoms; 4.6% of the effect was mediated via lower engagement in social activities (b = 0.005; 95% CI: 0.001-0.009). No mediation was detected through physical activity, smoking or alcohol consumption. Exploratory analyses revealed that the mediating role of social participation was more pronounced among participants with low household wealth (b = 0.012; 95% CI: 0.004-0.023; 7.3% mediated). Lower engagement in social activities partly explained the association between perceived neighbourhood crime and depressive symptoms in adults aged 50 years or older. Policies targeting disadvantaged communities to prevent crime and support social participation might be beneficial for population mental health, especially among financially vulnerable older residents.


Social determinants of multimorbidity in Jamaica: application of latent class analysis in a cross-sectional study.
Non-communicable disease (NCD) multimorbidity is associated with impaired functioning, lower quality of life and higher mortality. Susceptibility to accumulation of multiple NCDs is rooted in social, economic and cultural contexts, with important differences in the burden, patterns, and determinants of multimorbidity across settings. Despite high prevalence of individual NCDs within the Caribbean region, exploration of the social epidemiology of multimorbidity remains sparse. This study aimed to examine the social determinants of NCD multimorbidity in Jamaica, to better inform prevention and intervention strategies. Latent class analysis (LCA) was used to examine social determinants of identified multimorbidity patterns in a sample of 2551 respondents aged 15-74 years, from the nationally representative Jamaica Health and Lifestyle Survey 2007/2008. Multimorbidity measurement was based on self-reported presence/absence of 11 chronic conditions. Selection of social determinants of health (SDH) was informed by the World Health Organization's Commission on SDH framework. Multinomial logistic regression models were used to estimate the association between individual-level SDH and class membership. Approximately one-quarter of the sample (24.05%) were multimorbid. LCA revealed four distinct profiles: a Relatively Healthy class (52.70%), with a single or no morbidity; and three additional classes, characterized by varying degrees and patterns of multimorbidity, labelled Metabolic (30.88%), Vascular-Inflammatory (12.21%), and Respiratory (4.20%). Upon controlling for all SDH (Model 3), advancing age and recent healthcare visits remained significant predictors of all three multimorbidity patterns (p < 0.001). Private insurance coverage (relative risk ratio, RRR = 0.63; p < 0.01) and higher educational attainment (RRR = 0.73; p < 0.05) were associated with lower relative risk of belonging to the Metabolic class while being female was a significant independent predictor of Vascular-Inflammatory class membership (RRR = 2.54; p < 0.001). Material circumstances, namely housing conditions and features of the physical and neighbourhood environment, were not significant predictors of any multimorbidity class. This study provides a nuanced understanding of the social patterning of multimorbidity in Jamaica, identifying biological, health system, and structural determinants as key factors associated with specific multimorbidity profiles. Future research using longitudinal designs would aid understanding of disease trajectories and clarify the role of SDH in mitigating risk of accumulation of diseases.


Anion mediated, tunable isoguanosine self-assemblies: decoding the conformation influence and solvent effects.
Systematic investigations were performed with various substituted groups at C8 purine and ribose. A series of isoG analogs, C8-phenyl substituted isoG were synthesized and applied for Cs+ coordination. The structural proximity between purine and ribose limited pentaplex formation for C8-phenyl substituted isoG derivatives. Based on this observation, deoxy isoG derivative with modification on ribose (tert-butyldimethylsilyl ether) was applied to assemble with the Cs+ cation. Critical solvent (CDCl3 and CD3CN) and anion (BPh4 -, BARF-, and PF6 -) effects were revealed, leading to the controllable formation of various stable isoG pentaplexes, including singly charged decamer, doubly charged decamer, and 15-mer, etc. Finally, the X-ray crystal structure of [isoG20Cs3]3+(BARF-)3 was successfully obtained, which is the first example of multiple-layer deoxy isoG binding with the Cs+ cation, providing solid evidence of this new isoG ionophore beyond two-layer sandwich self-assembly.


c-Kit-negative fibroblast-like cells express platelet-derived growth factor receptor alpha in the murine gastrointestinal musculature.
Platelet-derived growth factor receptors (PDGFRs) belong to the same kinase group as c-Kit receptor tyrosine kinase that is specifically expressed in the interstitial cells of Cajal (ICC) in the gastrointestinal tract. In this study, we examined PDGFRalpha immunoreactivity in the murine gastrointestinal tract. PDGFRalpha-immunopositive (PDGFRalpha-ip) cells were observed in the musculature in all parts of the gastrointestinal tract. Although PDGFRalpha-ip cells were distinct from ICC and neurons, these cells were closely associated with intramuscular ICC and enteric nerve fibers. In the myenteric layer, PDGFRalpha-ip cells formed a cellular network with their ramified processes and encompassed myenteric ganglia. Numerous PDGFRalpha-ip cells were observed in the subserosal plane and showed a multipolar shape. The distribution pattern of the PDGFRalpha-ip cells in the ICC-deficient W(v)/W(v) mutant mice was the same as that in normal mice. PDGFRalpha-ip cells that showed intense immunoreactivity of SK3 potassium channel were considered to correspond to fibroblast-like cells or non-Cajal interstitial cells. Our observations suggest that PDGFRalpha-ip cells are basic cellular elements throughout the gastrointestinal musculature and are involved in the gastrointestinal functions.


Polarity Based Model for Guiding Medical School Strategy During Crisis - A Cross Sectional Qualitative Study.
Crises in academia can best be dealt with as a polarity that needs to be leveraged rather than a problem that needs to be solved. This work aimed at utilizing the Polarity Approach for Continuity and Transformation (PACT)™ to establish a guide for medical schools during times of crisis to minimize the effect of crisis-driven decisions on strategic growth. A qualitative study following the 5-Steps of the PACT process was conducted. A virtual mapping session was held with 108 medical educators from 22 countries to determine the upsides and downsides of strategic orientation and crisis management subsequently. Four polarity maps were generated identifying four tension areas; University reputation, mission, teams, and individuals followed by a 72-item assessment and another mapping session to map the warning signs and action steps. A comparison between private school scores and the whole cohort of respondents showed that private schools had the least problems in team-oriented work. This study highlighted the importance of taking measures to communicate the mission and supporting team functions inside universities either by enhancing resources or utilizing time and effort-saving strategies.


A programmable eddy-current compensation system for MRI and localized spectroscopy.
A programmable preemphasis system has been developed for eddy-current compensation in gradient sets with or without active screening. Preemphasis parameters are nonvolatile but can be changed rapidly when working with interchangeable gradient sets. The design allows easy retrofit to existing systems. A method for setting the preemphasis is presented, together with specimen results.


[Role of a change in oxygen concentration in modifying in vitro reproductive cell death. 3. Modification of radiosensitivity by compounds reducing oxygen].
The data are discussed concerning the protection of cells in vitro by the oxygen reducing agents. The analysis has demonstrated that the protective effect of sulfites can only be related to hypoxia they create. Hypoxia also contributes considerably to the protective effect of thiols (maximum DMF approximately 3). However the protective effect of thiols cannot wholly be attributed to hypoxia. The oxygen--independent component of the protective effect of thiols (maximum DMF approximately 1.5) is conditioned by the metabolic changes increasing the enzymic repair of potential damages.


Identifying and describing cancer survivors: Implications for cancer survivorship research and clinical care.
Gathering information directly from cancer survivors has advanced our understanding of the cancer survivorship experience. However, it is unknown whether surveys can distinguish important subgroups of cancer survivors. This study aimed to describe the current landscape of survey questions used to identify and describe cancer survivors in national cross-sectional studies. Using publicly available databases, the authors identified national cross-sectional surveys used in the United States within the past 15 years that included a question on self-reported history of cancer. After abstracting questions and response items used to identify cancer survivors, they conducted a descriptive analysis. The authors identified 14 national cross-sectional surveys, with half administered to the general population and the other half administered to cancer survivors. The most common question used to identify cancer survivors was "Have you ever been told by a doctor or other health professional that you had cancer?" Most surveys had questions asking participants to identify a single cancer type (n = 11), multiple prior cancer diagnoses or types (n = 11), and the time from diagnosis (n = 12). Treatment questions varied from active treatment status to specific treatments received. Questions addressing cancer stage (n = 2), subtypes (n = 1), metastatic status (n = 3), and recurrence (n = 4) were less frequently included. There is no standard method for assessing self-reported cancer history, and this limits the ability to distinguish among potentially important subgroups of survivors. Future cross-sectional surveys that capture nuanced data elements, such as cancer types, stages/subtypes, metastatic/recurrent status, and treatments received, can help to fill important gaps in cancer survivorship research and clinical care.


Effect of text message communication on patient presentation for an influenza vaccination in a community-based pharmacy setting.
Community pharmacies use text message communications for information regarding approaching refills and fill status. Patients can also be notified regarding annual influenza vaccine availability and schedule an appointment for the vaccine. This study aimed to evaluate whether text message communications affected patient presentation and resulted in a percent increase of patients receiving an influenza vaccine compared with previous vaccine season and to determine whether additional vaccines are administered upon presentation. Ambidirectional study retrospectively analyzed the impact, nationally, of a new text message communication on influenza vaccinations at a large community pharmacy chain and prospectively surveyed patients receiving an influenza vaccine at 2 geographically similar pharmacies of the chain in Southwest Virginia. Text message communications regarding vaccine and appointment availability were sent to patients at the age of 18 years and older who opted in to text message communications and received an influenza vaccine with the chain during the 2019-2020 influenza season. Vaccine data from consecutive seasons were compared. Eligible patients in Southwest Virginia were surveyed about how they were informed about availability, previous intent to receive an influenza vaccine, applicability to other vaccines, and effect of the coronavirus disease 2019 pandemic on vaccination. Results were analyzed using bivariate and multivariate analyses. Nationally, influenza vaccines administered increased by 17.45% in patients who permitted text message communication and overall by 13.22% after implementation. Decreases in co-administered pneumococcal vaccines and tetanus, diphtheria, and pertussis vaccines and an increase in co-administered zoster vaccines were observed. A total of 111 patients were surveyed; 4% presented owing to text message communication. A majority were intent on receiving the vaccine before being notified and reported that the pandemic did not affect presentation. Notably, 45.05% of patients were likely to receive routine vaccines if notified by text message. Text message communications are another viable way to increase vaccinations, but further studies should be conducted outside of a pandemic setting.


Practicing logical reasoning through Drosophila segmentation gene mutants.
Laboratory practical sessions are critical to scientific training in biology but usually fail to promote logical and hypothesis-driven reasoning and rely heavily on the teacher's instructions. This paper describes a 2-day laboratory practicum in which students prepare and analyze larval cuticle preparations of Drosophila segmentation gene mutant strains. Embryonic segmentation involves three major classes of genes according to their loss-of-function phenotypes: the establishment of broad regions by gap genes, the specification of the segments by the pair-rule genes, and the compartments within segments by the segment polarity genes. Students are asked to sort undefined segmentation mutants into gap, pair-rule, or segment polarity categories based on their knowledge of the Drosophila segmentation process and the microscopic anatomical traits they are capable of finding in the sample preparations. This technically simple practicum prompts students to pay attention to detailed observation to detect anatomic markers of intrasegmental compartments and thorax versus abdomen cuticle, and promote their logical reasoning in hypothesizing to which segmentation type a given mutant fits best.


Preventive effect of low-carbohydrate high-fat dietary pattern on liver disease caused by alcohol consumption via a 6pgd-involved mechanism in mice.
A low-carbohydrate high-fat (LCHF) dietary pattern has been reported to improve chronic metabolic diseases. However, whether and how the LCHF diet affects the pathological progression in patients with alcohol-related liver diseases (ALD) is largely unknown. This study was conducted to evaluate the effect of the LCHF diet on ALD and clarify its potential mechanism(s). The ALD model was established by feeding C57BL/6N mice with a Lieber-DeCarli liquid alcohol diet with a modified carbohydrate/fat ratio under an isoenergetic pattern. After an eight-week intervention, we observed that the LCHF diet significantly reduced alcohol-induced hepatic steatosis and liver injury, along with improved lipid metabolic-related gene disorders and redox imbalance. The alcohol-stimulated increase in pro-inflammatory cytokine cytokines expression, including TNF-α, IL-1β, and IL-6, was markedly reversed by the LCHF diet. Liver transcriptome sequencing and qPCR validation showed that twenty-four alcohol-disturbed genes were significantly reversed by LCHF-diet intervention. The top differentially expressed genes were selected for further investigation. Among them, 6-phosphogluconate dehydrogenase (6PGD) was significantly up-regulated by alcohol treatment in both the liver and cultured hepatocytes. Spearman correlation analysis revealed that 6PGD was positively associated with hepatic steatosis, liver injury, and oxidative stress indexes. In vitro, the 6PGD knockdown ameliorated alcohol-induced hepatotoxicity and intracellular lipid accumulation, as well as lipid metabolic-related gene disorders, implying the involvement of 6PGD in LCHF-protected ALD. In conclusion, LCHF diet intervention alleviated chronic alcohol consumption-induced liver dysfunction in mice. 6PGD is a potential novel target for ALD prevention that contributes to LCHF-improved ALD. A LCHF diet might be a promising choice for ALD management.


Landiolol in the treatment of the intraoperative supraventricular tachycardia: a multicenter, randomized, double-blind, placebo-controlled study.
Supraventricular tachycardia during the induction of anesthesia may carry a higher risk. The aim of this study was to evaluate efficacy and safety of intravenous landiolol in Chinese patients with intraoperative supraventricular tachycardia during anesthesia. A randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase 2 study. Eight sites of Chinese hospitals. Men and women aged 18 to 70 years with the intraoperative supraventricular tachycardia (heart rate [HR], ≥100 beats/min) or the supraventricular tachycardia outside of the sinus tachycardia lasting more than 1 minute. Patients received landiolol or placebo-0.125 mg kg(-1) min(-1) (1 minute) loading→0.04 mg kg(-1) min(-1) (10 minutes) continuous. The proportion of patients receiving rescue medication (esmolol) when the reduction of HR did not exceed 10% after intravenous landiolol for 5 minutes. Other secondary efficacy end points include HR, blood pressure, rate pressure product, and electrocardiogram; the improvement of supraventricular tachycardia; the time it takes for the decrease of the HR to reach more than 10%; and the time it takes for the HR to reach <100 beats/min. Efficacy and safety were evaluated for 240 patients who received study drug. Lower proportions of patients received rescue medication in the landiolol group (7.63%) compared with that in the placebo group (80.33%) (P < .0001). Suppression of HR and rate pressure product was generally more potent(P < .0001), and higher proportions of patients improved supraventricular tachycardia (P < .0001) in the landiolol group. The most frequent adverse event was hypotension. Intravenous landiolol (loading dose of 0.125 mg/kg) may effectively control intraoperative supraventricular tachycardia during anesthesia. It inhibited the increases in HR during the induction of anesthesia. The effect of landiolol on blood pressure was minimal without decreasing diastolic blood pressure and with the minor reduction of systolic blood pressure (ClinicalTrials.gov number, ChiCTR-TRC-12003021).


Concurrent chemotherapy and adjuvant extended field irradiation after radical surgery for cervical cancer patients with lymph node metastases.
The purpose of this retrospective study was to report our experience with concurrent chemotherapy and adjuvant extended field irradiation after radical surgery for cervical carcinoma patients with common iliac node and/or multiple pelvic lymph nodes metastases. We studied 25 patients with FIGO stage IB-IIB (IB, 3; IIA, 15; and IIB, 7) cervical carcinoma who underwent radical surgery and had histologically confirmed involvement of common iliac nodes and/or multiple (>or=2) pelvic lymph nodes. These patients received the first cycle of systemic chemotherapy 2 weeks after radical surgery. Then, they received pelvic and extended field irradiation (40-45 Gy) with weekly cisplatinum (30 mg/m(2)). They were then given five more cycles of consolidation chemotherapy. Survival curves were generated by the Kaplan-Meier method. The 3-year progression-free survival (PFS) and overall survival rates were 63% and 76%, respectively. The PFS rates with multiple pelvic node and common iliac node metastases were 69% and 61%, respectively. The pelvic recurrence rate was 8% (2/25) and that for distant metastases was 32% (8/25). No patient's treatment failed in the para-aortic region. The median interval from the surgery to the recurrence was 14 months (range, 5-29 months). Nineteen (76%) patients experienced grades 1-2 and four (16%) experienced grades 3-4 neutropenia. Fifteen patients (60%) experienced grades 1-2 and one (4%) experienced grades 3-4 gastrointestinal toxicity. Concurrent chemotherapy and adjuvant extended field irradiation after radical surgery achieved good local control with acceptable toxicity. However, subsequent distant metastasis was still the predominant form of treatment failure even after consolidation chemotherapy.


Surgical Management of Vertex Epidural Hematoma: Technical Case Report and Literature Review.
Vertex epidural hematoma (VEH) is an uncommon presentation of extra-axial hematomas. It can represent a surgical dilemma regarding when and how to operate, particularly considering the potential implication of the superior sagittal sinus (SSS). Here, we illustrate the surgical technique for VEH as well as a review of the existing literature. A 60-year-old man sustained a ground-level fall resulting in complete diastasis of the sagittal suture with underlying large VEH causing significant mass effect on the SSS and bihemispheric convexities. Twenty-four hours later, the patient deteriorated, with decreased level of alertness and worsening asymmetric paresis on his lower extremities. He subsequently underwent surgical evacuation of the hematoma, decompression of the SSS, and fracture repair. A modified bicoronal approach, with bilateral parasagittal craniotomies, was performed. A central island of bone was left intact to spare the diastatic fracture from the craniotomies. This was done to ensure a stable anchor point for tacking-up the underlying displaced dura and SSS. The central bone prevents extensive bleeding from the diastatic fracture and eliminates the risk of further blood reaccumulation and tearing of a possible injured sinus during bone flap elevation. The technique performed allowed us to evacuate completely the hematoma while preserving the SSS and repairing the sagittal suture to avoid further bleeding. Complete neurologic recovery of the patient occurred after VEH evacuation. Because of its rare nature, VEH represents a surgical challenge. Because neurosurgeons encounter this condition relatively infrequently, literature regarding the medical and surgical management of this entity is warranted.


Accuracy of B-type natriuretic peptide levels in the diagnosis of left ventricular dysfunction and heart failure: a systematic review.
To evaluate the accuracy of B-type natriuretic peptide levels (BNP) in the diagnosis of heart failure and left ventricular dysfunction. Electronic search in Medline, Embase, Cochrane Library and Medion database, and hand search of reference lists. We have included published studies on the accuracy of BNP which had both sufficient information to construct the 2x2 diagnostic cross table and an appropriate spectrum of patients. Fifty five studies (16,730 patients) were analyzed. The main determinants of diagnostic accuracy were the reference standard analyzed (clinical heart failure versus left ventricular dysfunction), and the methodological quality of the study. BNP levels were highly accurate for the diagnosis of clinical heart failure (diagnostic OR=41; 95% CI 23-74). The negative likelihood ratios were homogeneous, and useful for excluding the existence of heart failure (pooled negative likelihood ratio=0.11; 95% CI 0.08-0.16). The studies focused on the identification of left ventricular dysfunction were heterogeneous, with indications of publication bias, and showed less overall diagnostic accuracy than studies focused on heart failure. BNP levels are useful for ruling out heart failure. The accuracy of BNP for identifying patients with systolic dysfunction is more limited.


Expression of Bax, a pro-apoptotic member of the Bcl-2 family, in esophageal squamous cell carcinoma.
Samples of normal esophageal squamous epithelium (n = 10), severe squamous cell dysplasia (n = 22), carcinoma in situ (n = 15), invasive squamous cell carcinoma (n = 172), lymph-node metastasis (n = 21) and 2 permanent esophageal squamous cell carcinoma cell lines were analyzed immunohistochemically for Bax expression using a polyclonal anti-Bax antibody. Immunostaining was evaluated according to a score system (0-8 points) based on the percentage of positive tumor cells and the relative immunostaining intensity. Cytoplasmatic staining for Bax protein was found uniformly in all cell layers of the normal esophageal squamous epithelium. In contrast, a gradual loss of immunoreactivity for Bax was found in a fraction of pre-neoplastic and neoplastic lesions. Upon comparison of the amount of Bax expression between the different types of lesion, however, no significant differences were found between severe squamous cell dysplasias, carcinomas in situ, invasive carcinomas and lymph-node metastases. In both esophageal carcinoma cell lines, immunoreactivity for Bax was found and confirmed by means of Northern blot analysis. In invasive carcinomas, Bax immunoreactivity was inversely correlated with Bcl-2 expression (p = 0.0243) and decreased continuously with decreasing tumor differentiation (p = 0.0011). No correlation was found between Bax expression and the following parameters: depth of invasion, nodal status and tumor size. Bax expression had no influence on the post-operative survival of esophageal cancer patients.


Identification of novel pyrrolopyrazoles as protein kinase C β II inhibitors.
A novel series of pyrrolopyrazole-based protein kinase C β II inhibitors has been identified from high-throughput screening. Herein, we report our initial structure-activity relationship studies with a focus on optimizing compound ligand efficiency and physicochemical properties, which has led to potent inhibitors with good cell permeability.


Ultrastructure of the microvasculature in human endometrial hyperplasia.
Our purpose was to determine the effect of hyperplasia on cell-to-cell communication in the microvasculature of the human endometrium. Ten biopsy specimens of simple and complex hyperplasia of the human endometrium were investigated by electron microscopy. The microvasculature of the hyperplastic endometrium shows morphologic disorder. The extracellular matrix is altered, and cell death is widespread. Intercellular contact is infrequent or absent. These results are in marked contrast to the ultrastructure of the normal microvasculature. The complex cell-to-cell interaction observed in normal tissue appears lost. This report, combined with others, indicates that cell-to-cell contact is sparse in hyperplastic endometrium.


Cadmium activates extracellular signal-regulated kinase 5 in HK-2 human renal proximal tubular cells.
We examined the effects of cadmium chloride (CdCl(2)) exposure on the phosphorylation and functionality of extracellular signal-regulated kinase 5 (ERK5), a recently identified member of the mitogen-activated protein kinase (MAPK) family, in HK-2 human renal proximal tubular cells. Following exposure to CdCl(2), ERK5 phosphorylation increased markedly, but the level of total ERK5 was unchanged. ERK5 phosphorylation following CdCl(2) exposure was rapid and transient, similar to the time course of ERK1/2 phosphorylation. Treatment of HK-2 cells with the MAPK/ERK kinase 5 inhibitor, BIX02189, suppressed CdCl(2)-induced ERK5 but not ERK1/2 phosphorylation. The CdCl(2)-induced increase of phosphorylated cAMP response element-binding protein (CREB) and activating transcription factor-1 (ATF-1), as well as the accumulation of mobility-shifted c-Fos protein, were suppressed by BIX02189 treatment. Furthermore, BIX02189 treatment enhanced cleavage of poly(ADP-ribose) polymerase and increased the level of cytoplasmic nucleosomes in HK-2 cells exposed to CdCl(2). These findings suggest that ERK5 pathway activation by CdCl(2) exposure might induce the phosphorylation of cell survival-transcription factors, such as CREB, ATF-1, and c-Fos, and may exert a partial anti-apoptotic role in HK-2 cells.


A manganese-containing superoxide dismutase from Paracoccus denitrificans.
A cyanide-insensitive superoxide dismutase (superoxide: superoxide dismutase EC 184.108.40.206) has been isolated from Paracoccus denitrificans, purified to homogeneity and characterized. It is a soluble, manganese-containing protein with an apparent molecular weight of 41 500 +/- 1000. It is composed of two identical subunits (Mr 23 500) not bound by disulfide linkage. It's isoelectric point is 4.5. The amino acid composition shows strong similarities with other dimeric procaryotic and with tetrameric mitochondrial Mn-superoxide dismutases. The fully active enzyme contained from 1.34 to 2 gatom Mn/mol enzyme.


Electrical Properties of Model Lipid Membranes.
Biological membranes are essential components of the living systems, and processes occurring with their participation are related mainly to electric phenomena such as signal transduction, existence of membrane potentials, and transport through the membrane [...].


Selecting flagship species to solve a biodiversity conservation conundrum.
The difficulty of effectively monitoring and managing the environment to conserve biodiversity is as yet an unsolved conundrum. A project of the Chinese Academy of Sciences has concluded that progress can be made through the use of flagship species selected using criteria drawn from conservation biology, ecosystem function, socio-economics, and cultural importance. Inclusion of the latter three criteria will help attract and maintain the commitment of the public to play full parts in carrying out any conservation measures needed. A system is proposed for scoring species to select those that are most suitable as flagships. This method can be used regardless of the size of the area chosen for attention, whether it is a region, a country, or a particular protected area.


Effects of pyrobenzamine and plimasin on fighter pilots flying a fighter intercept mission in the F4D flight simulator.
There were 26 F4D crews from a Tactical Air Force Wing which participated in a difficult intercept mission in a F4D flight simulator. They were divided into three groups, medicated with either Plimasin, Pyrobenzamine or placebo. The groups medicated with either Plimasin or Pyrobenzamine alone demonstrated decreased effectiveness in completing this intercept as compared with the nonmedicated group. These medications apparently caused impairment of mission performance and should be avoided while performing flying duties.


Documentation of do-not-resuscitate orders in an Irish hospital.
Some studies have suggested that do-not-resuscitate (DNR) decisions are often documented poorly in European countries. To examine the use and documentation of DNR orders in a large Irish teaching hospital. Resuscitation status of all inpatients on a single day was determined using interviews with nursing staff and examination of the nursing and medical case notes. Seventeen (3.5%) of 485 patients were identified as not for resuscitation. There was written confirmation of the DNR order in the nursing notes for 14 (82%) and in the medical notes for 15 (88%) patients; in two cases, it was reported that doctors were reluctant to write down the agreed decision. Documentation of DNR orders was by consultant (7), registrar (7) and intern (1). Discussion with patient (2), family (10) or both (1) was recorded in 14 cases. The majority of DNR orders were clearly documented by senior doctors and had been discussed with the patient or with the relatives. A number of problems were identified that might be avoided by development of guidelines regarding use and documentation of DNR orders.


Combined effect of inorganic carbon limitation and inhibition by free ammonia and free nitrous acid on ammonia oxidizing bacteria.
The inhibitory effect of free ammonia (NH(3) or FA) and free nitrous acid (HNO(2) or FNA) on the ammonia oxidizing bacteria (AOB) and the dependence of the AOB activity on the concentration of total inorganic carbon (TIC) are well-established. In contrast, less is know about the effect of high FA and FNA concentrations in combination with TIC limitation. Respirometric tests performed with an enriched AOB sludge (81% of AOB as measured with fluorescent in situ hybridization) established that AOB inhibition by FA under TIC limitation was higher than under non-limiting TIC conditions (Haldane inhibition coefficients of 139 and 376 mg NH(3)L(-1)). AOB affinity for FA decreased under TIC limitation conditions (half-saturation coefficient of 0.28 mg NH(3)L(-1) without TIC limitation and 4.3 mg NH(3)L(-1) with TIC limitation). Higher inhibition by FNA was observed when TIC was limited since the non-competitive inhibition coefficient decreased from 1.31 mg HNO(2)L(-1) (without TIC limitation) to 0.21 mg HNO(2)L(-1) (with TIC limitation). This study demonstrates that AOB inhibitions by FA and FNA are amplified with TIC limitation and consequently, AOB dynamics are strongly modified under TIC limitation conditions.


Effects of a lifestyle-related risk factor modification intervention on lifestyle changes among patients with coronary artery disease in Nepal.
To investigate the effect of a lifestyle-related risk factor modification intervention on coronary artery disease (CAD) patients' lifestyle changes. A randomized controlled study was conducted in Nepal. A total of 224 CAD patients (112 in each study group) were included at baseline, and 196 patients (98 in each group) completed the one-month follow-up. Patients in the intervention group (IG) received nurse-led intervention in addition to the usual care. Face-to face and telephone interview was conducted using standard questionnaires to collect data on lifestyle-related risk factors; smoking, alcohol consumption, diet, body mass index, stress, adherence to medical therapy, and physical activity. General linear model repeated measure analysis was used to analyse the effects of the intervention. Based on self-reported data we found significant improvement in lifestyle-related risk factor habits in the IG compared with the usual care group with respect to diet (p < 0.001), physical activity (p < 0.001), medication adherence (p < 0.001) and stress (p < 0.001) at one-month follow-up. Lifestyle-related risk factor modification intervention can positively influence health risk habits, even when it is less intensive but supplemented with information leaflets. Nurse-led one-time intervention may successfully deliver counselling to improve healthy lifestyle among underserved CAD patients.


Splenic marginal zone B-cell lymphoma associated with ruptured breast implants: case report and review of the literature.
We describe splenomegaly and bilateral grade 2 Baker breast capsular contracture in a woman who had undergone augmentation mammoplasty. This case represents the first documented instance of splenic marginal zone lymphoma, and is among the rare reports of B-cell lymphoma, arising in a patient with breast implants.


Iodine-catalyzed oxidative annulation: facile synthesis of pyrazolooxepinopyrazolones via methyl azaarene sp3 C-H functionalization.
An iodine-catalyzed methyl azaarene sp3 C-H functionalization has been developed for the synthesis of a seven-membered O-heterocyclic architecture containing three different heterocyclic aromatic hydrocarbons. This method can be applied to a wide range of substituted methyl azaarenes and diverse 2,4-dihydro-3H-pyrazol-3-ones, and brings about the efficient preparation of 2,9-dihydrooxepino[2,3-c:6,5-c']dipyrazol-3(7H)-ones in high yields with the merits of low catalyst loading, good functional group tolerance and metal-free conditions.


Saddle-shape annuloplasty increases mitral leaflet coaptation after repair for flail posterior leaflet.
The primary goal of surgical mitral repair is the reestablishment of normal leaflet coaptation. Surgical techniques that maintain or restore leaflet geometry promote leaflet coaptation. Recent 3-dimensional (3D) echocardiographic studies have shown that saddle-shaped annuloplasty has a salutary influence on leaflet geometry. Therefore we hypothesized that saddle-shaped annuloplasty would improve leaflet coaptation in cases of repair for flail posterior leaflet segments. Sixteen patients with flail posterior segment and severe mitral regurgitation had valve repair using standard techniques. Eight patients received saddle-shaped annuloplasty and 8 patients received flat annuloplasty. Real-time 3D transesophageal echocardiography was performed before and after repair. Images were analyzed using custom software to calculate mitral annular area (MAA), septolateral dimension (SLD), intercommissural width (CW), total leaflet area (TLA), and leaflet coaptation area (LCA). Postrepair MAA (flat, 588.6±26.5 mm2; saddle, 628.0±35.3 mm2; p=0.12) and TLA (flat, 2198.5±151.6 mm2; saddle, 2303.9±183.8 mm2; p=0.67) were similar in both groups. Postrepair LCA was significantly greater in the saddle group than in the flat group (226.8±24.0 mm2 and 154.0±13.0 mm2, respectively; p=0.02). Real-time 3D echocardiography and novel imaging software provide a powerful tool for analyzing mitral leaflet coaptation. When compared with flat annuloplasty, saddle-shaped annuloplasty improves LCA after mitral valve repair for severe mitral regurgitation secondary to flail posterior leaflet segment. Use of saddle-shaped annuloplasty devices may increase repair durability.


Survival after surgical resection for high-grade chest wall sarcomas.
Indications for chest wall resection of metastatic or locally recurrent sarcoma and for subsequent bony reconstruction are controversial. Twenty-eight patients had chest wall resection for high-grade primary, metastatic, or recurrent sarcoma. In all patients, resection with selective reconstruction of the bony thorax was performed without operative mortality. Since 1980, only patients with four or more ribs resected have had selective bony reconstruction. Follow-up ranged from 8 to 132 months (median follow-up, 42 months). All deaths were related to sarcoma recurrence. The overall actuarial survival rate was 85% at 1 year, 65% at 3 years, and 59% at more than 5 years. The overall actuarial proportion without disease recurrence was 64% at 1 year, 52% at 3 years, and 40% at more than 5 years. There was no significant difference in overall or disease-free survival for patients with primary, metastatic, or recurrent tumors. The most important prognostic factors were positive margins and concomitant pulmonary resection for synchronous lung metastases. These data support aggressive resection to obtain pathologically tumor-free margins for chest wall sarcomas, whether primary, metastatic or recurrent. Reconstruction can be individualized based on the extent of resection.


Are there clinical and epidemiological differences between familial and non-familial Alzheimer's disease?
To determine whether there are clinical and epidemiological differences between familial and non-familial Alzheimer's disease, we studied 151 patients with the clinical diagnosis of Dementia of the Alzheimer Type (DAT). Eighty-four index patients (56%) had at least one relative with reported DAT-type memory loss; the remaining 67 did not. For comparison, patients with a positive family history were grouped into a suspected familial DAT (FDAT), and those with a negative family history were grouped into a suspected non-familial DAT (NFDAT). There were no significant differences between FDAT and NFDAT patients with respect to age of symptom onset, survival time, rate of cognitive decline, motor function, behavioral signs or symptoms, head trauma, thyroid dysfunction, maternal age, or birth order. There were no significant differences between pedigrees of FDAT and NFDAT patients in respect to the prevalence of Down's syndrome or age of mortality. To examine a more "familial" set of FDAT patients, an FDAT subgroup (F2DAT) consisting of 33 index patients with two or more affected relatives with DAT-type memory loss was compared to the 67 NFDAT patients in a similar analysis. No significant differences were found. However, NFDAT index patients had a higher reported prevalence of head trauma than those patients in the F2DAT subgroup (NFDAT 22%, F2DAT 7%, OR = 4.2, CI = 0.9-20.0, P = 0.08). Thus severe head trauma may be a more important etiological factor in the non-familial form of DAT. To better examine this tendency, future studies should be conducted utilizing a larger number of pedigrees and familial criteria which account for the number of persons at risk and the age at onset of disease.


Endoscopic removal of retained bile duct calculi via T-tube tract.
A simple and safe technique for removal of retained bile duct calculi using a flexible fibreoptic choledochoscope and rigid nephroscope via the T-tube tract has been described. The technique allowed removal of large impacted calculi under direct vision without damage to the bile duct.


Vasopressin and conditioned flavor aversion in aged rats.
The effect of lysine vasopressin on the performance of young-adult and old rats subjected to a conditioned flavor aversion procedure was studied. Young rats maintained an aversion to a 0.1% saccharin solution significantly longer than did older rats. Treatment with lysine vasopressin ( 1 microgram/kg) during the recovery period prolonged the aversion in both age groups. A single injection of lysine vasopressin prior to the aversion procedure significantly reduced the age difference in extinction. These observations support the hypothesis that age-dependent changes in endogenous vasopressin synthesis or secretion underlie some of the behavioral deficits observed in old animals.


Predictors of engaging in voluntary work during the COVID-19 pandemic: analyses of data from 31,890 adults in the UK.
As the COVID-19 pandemic has grown internationally, there has been an increased need for volunteers. This study aimed to identify the predictors of volunteering including demographic backgrounds, socio-economic characteristics, personality, and psychosocial factors. Data were analysed from 31,890 adults in the UK COVID-19 Social Study run by the University College London - a longitudinal study focusing on the psychological and social experiences of adults living in the UK during the COVID-19 pandemic. Tetrachoric factor analysis was applied to identify latent categories of voluntary work. Multivariate logistic regression was used to identity predictors for volunteering and change in volunteering behaviours since before the COVID-19 pandemic. Three types of volunteering during the pandemic were identified as follows: formal volunteering, social action volunteering, and neighbourhood volunteering. Regression analysis showed that the pattern of voluntary work was structured by demographic backgrounds, socio-economic factors, personality, and psychosocial factors. The predictors of volunteering during the pandemic may be slightly different from other non-emergency period.


DExD/H-box RNA helicase genes are differentially expressed between males and females during the critical period of male sex differentiation in channel catfish.
DExD/H-box RNA helicases are motor proteins participating in nearly all aspects of cellular processes, especially in RNA metabolism. In this study, a total of 54 DExD/H-box RNA helicase genes including 37 DDX (DEAD-box) and 17 DHX (DEAH-box) genes were characterized in channel catfish (Ictalurus punctatus), and annotated through phylogenetic and syntenic analyses. All the catfish RNA helicases contained conserved helicase signature motifs, demonstrating that the RNA helicase gene family was highly conserved. Analysis of the relative rates of synonymous (dS) and nonsynonymous (dN) substitutions revealed that the RNA helicase genes were subjected to strong negative (purifying) selection. Meta-analysis was conducted to determine expression of the RNA helicase genes during the critical period (90-110days post-fertilization, dpf) of male gonad differentiation. At 90dpf, 24 RNA helicase genes were highly differentially expressed in the gonad tissues between the males and females; similarly, 24 and 18 RNA helicase genes were found highly differentially expressed in the gonad tissues between the males and females at 100 and 110dpf, respectively (p<0.01). In general, the vast majority of the RNA helicase genes (31) were expressed at higher levels in females than in males. In the male gonad, a set of 8 RNA helicases were expressed at a significantly higher level at 110dpf than at 90dpf. These findings suggested that RNA helicases may play important roles in sex development and differentiation in teleosts.


Adolescent cavitary tuberculosis. Secondary case finding using a social contact scale.
The spread of tuberculosis in a university environment following a case of cavitary disease was studied. Six loci of potential secondary infection were ascertained and the persons at risk were identified for tuberculin screening. All named contacts were ranked by the index patient and her friends on a closeness scale for social contact. This scale proved to be an excellent predictor of tuberculin positivity, suggesting that in a noninstitutionalized setting the risk of tuberculin conversion is associated more with social contact than with mere living proximity.


Synchronous computed tomography-guided percutaneous biopsy and microwave ablation for highly suspicious malignant lung ground-glass opacities adjacent to mediastinum.
This retrospective study aimed to assess the safety and efficacy of synchronous biopsy and microwave ablation (MWA) for highly suspected malignant lung ground-glass opacities (GGOs) adjacent to the mediastinum (distance ≤10 mm). Ninety patients with 98 GGOs (diameter range, 6-30 mm), located within 10 mm of the mediastinum, underwent synchronous biopsy and MWA at a single institution from 1 May 2020, to 31 October 2021 and were enrolled in this study. Synchronous biopsy and MWA involving the completion of the biopsy and MWA in a single procedure was performed. Safety, technical success rate, and local progression-free survival (LPFS) were evaluated. The risk factors for local progression were calculated using the Mann-Whitney U test. The technical success rate was 97.96% (96/98 patients). The LPFS rates at 3, 6, and 12 months were 95.0%, 90.0%, and 82.0%, respectively. The diagnostic rate of biopsy-proven malignancy was 72.45% (n = 71/98). Invasion of lesions into the mediastinum was a risk factor for local progression (p = 0.0077). The 30-day mortality rate was 0. The major complications were pneumothorax (13.27%), ventricular arrhythmias (3.06%), pleural effusion (1.02%), hemoptysis (1.02%), and infection (1.02%). Minor complications included pneumothorax (30.61%), pleural effusion (24.49%), hemoptysis (18.37%), ventricular arrhythmias (11.22%), structural changes in adjacent organs (3.06%), and infection (3.06%). Synchronous biopsy and MWA was effective for treating GGOs adjacent to the mediastinum without severe complications (Society of Interventional Radiology classification E or F). Invasion of lesions into the mediastinum was identified as a risk factor for local progression.


Longer mtDNA Fragments Provide a Better Insight into the Genetic Diversity of the Sycamore Lace Bug, Corythucha ciliata (Say, 1832) (Tingidae, Hemiptera), Both in Its Native and Invaded Areas.
The sycamore lace bug (Corythucha ciliata Say, 1832) is of North American origin, but after its introduction to Europe (1964), South America (1985), Asia (1995), Australia (2006), and Africa (2014), it became an abundant and widespread pest on plane (Platanus spp.) trees. We analysed a 1356 bp long fragment of the mtDNA (COI gene) of 327 sycamore lace bug individuals from 38 geographic locations from Europe, Asia, and North America. Seventeen haplotypes (17 HTs) were detected. C. ciliata populations from North America exhibited higher haplotype diversity (12 HTs) than populations from Europe (6 HTs), Asia (4 HTs), or Japan (2 HTs). The haplotypes formed two haplogroups separated by at least seven mutation steps. One of these mutation steps includes HTs from North America and Japan. Another includes HTs from North America, Europe, and Asia. Haplotypes from Asia Minor, the Caucasus, and Central Asia are linked to haplotypes from Europe, while haplotypes found in Japan are linked to haplotypes found in North America only. The incorporation of published data from the GenBank into our dataset (altogether 517 individuals from 57 locations, but only 546 bp long fragment of the mtDNA) did not show any structure according to the geographic origin of the individuals.


Immune responses after acute ischemic stroke or myocardial infarction.
We recently demonstrated an immediate immunodepressive state after acute ischemic stroke in humans. In the present study, we prospectively analyzed immune responses in patients with middle cerebral artery stroke (n=20), acute myocardial infarction (n=20) and healthy controls (n=20, also matched for age and gender). Compared to controls, a rapid depression of monocytic HLA-DR expression and a defective lymphocytic IFN-γ production was obvious after ischemic stroke or myocardial infarction, while total counts of leukocytes and monocytes were significantly higher after myocardial infarction. A T cell-mediated lymphopenia was accentuated in patients with severe stroke, obviously predisposing these patients for nosocomial infections. Our data reveal an immediate and to some extent differential suppression of cell-mediated immune responses after ischemic stroke or myocardial infarction respectively.


Ultrasound backscatter at 30 MHz from human blood: influence of rouleau size affected by blood modification and shear rate.
High frequency intravascular ultrasound may show a high intensity backscatter from blood which hampers the discrimination between lumen and arterial wall. In this study, the acoustic behaviour of blood at 30 MHz in relation to rouleau size was analyzed. In a Couette viscometer, high frequency (20-40 MHz) backscatter data from normal and modified blood samples from eight volunteers were obtained at shear rates from 0 to 1000 s-1. The acoustic behaviour of blood was quantified by the integrated backscatter power and the spectral slope of the backscatter coefficient. Backscatter from blood depended on rouleau size. At a shear rate of zero, both whole blood and rouleau-enhanced blood showed a 11-dB-higher integrated backscatter power than rouleau-suppressed blood, which itself was 10 dB higher than that of hemolysed blood, the latter showing a 6-dB-higher backscatter than saline. Platelets did not contribute to the backscatter power. Plasma and saline produced no detectable integrated backscatter power other than noise. The spectral slope of whole and rouleau-enhanced blood was small (1 and 0.5, respectively), whereas rouleau-suppressed blood and hemolysed blood (both with a slope of 3.3) behaved almost like a Rayleigh scattering medium (slope = 4). The backscatter from rouleau-suppressed blood showed no shear rate dependence. At low shear rates ( < 0.8 s-1 for integrated backscatter power and < 0.2 s-1 for the spectral slope), whole blood and rouleau-enhanced blood tended to the results from the static situation (no shear). At high shear rates ( > 80 s-1 for integrated backscatter power and >11 s-1 for spectral slope), these samples tended to the results of rouleau-suppressed blood. Ultrasound backscatter at 30 MHz from human blood is only caused by red blood cells. With increasing aggregate (rouleau) size, the integrated backscatter power increased by 11 dB, and the spectral slope decreased from 3.3 to 1.


A safe and efficient synthetic method for alkali metal octahydrotriborates, unravelling a general mechanism for constructing the delta B3 unit of polyhedral boranes.
A safe and efficient synthetic method for MB3H8 (M = Na, K, Rb and Cs) has been developed with excellent yields by directly reacting the corresponding MBH4 with the dimethyl sulfide borane complex (DMS·BH3). A general mechanism for constructing B3H8-, a basic unit for building polyhedral boranes, has been unravelled.


Prospective evaluation of the retrograde percutaneous translaryngeal tracheostomy (Fantoni procedure) in a surgical intensive care unit: technique and results of the Fantoni tracheostomy.
Controversy surrounds the safety and practicality of the retrograde percutaneous translaryngeal tracheostomy (Fantoni procedure) compared with other percutaneous methods. We used the Fantoni tracheostomy for 245 patients in our intensive care unit (ICU) over a period of 3 years 6 months and conducted a prospective analysis. We are able to report a low incidence of complications (1.2%) with the Fantoni procedure. Advantages of the method are reduced tissue trauma and optimal adaptation of the stoma to the cannula, leading to less stomal bleeding and fewer infectious complications. We observed no procedure-related mortality. Under mandatory bronchoscopic control, proper puncture location and cannula placement are ensured, which prevents tracheal wall injury and paratracheal placement of the cannula. Our experience shows that the major advantage of the use of the Fantoni tracheostomy is the retrograde dilatation of the stoma, which prevents serious complications compared with other techniques.


Medication persistence of targeted immunomodulators for plaque psoriasis: A retrospective analysis using a U.S. claims database.
Studies of medication persistence in plaque psoriasis have shown inconsistent results, likely due to differing definitions of nonpersistence and of the permissible gap between refills. Also, medication persistence information for two recently approved drugs, apremilast and ixekizumab, is limited. We use the Truven Health MarketScan claims database to assess persistence for six drugs: adalimumab, apremilast, etanercept, ixekizumab, secukinumab, and ustekinumab. We define the permissible gap in three ways: 150 days for ustekinumab and 90 days for all other drugs (150/90 model); 120 days for all drugs (120 model); and twice the days' supply for all drugs (days' supply model). To estimate unadjusted persistence, we use Kaplan-Meier curves, and a proportional hazards model to estimate the adjusted risk of non-persistence. Ustekinumab is most sensitive to changes in the definition of permissible gap, likely because of its longer maintenance dosing interval. Among targeted drug-experienced patients using ustekinumab, median persistence is 358 days (95% confidence interval: 343-371) in the 150/90 model and 189 days (179-199) in the days' supply model. Among targeted drug-experienced patients, median persistence in the days' supply model is longest for ixekizumab and secukinumab at 252 (217-301) and 222 (210-244) days, respectively. We also find that adjusted risk of nonpersistence increases by approximately 1% per year at treatment start. The definition of permissible gap meaningfully changes both absolute and ordinal estimates of medication persistence. Each definition has unique limitations, which should be considered when interpreting persistence data.


Injectable Asymmetric Adhesive-Antifouling Bifunctional Hydrogel for Peritoneal Adhesion Prevention.
Peritoneal adhesion is a common problem after abdominal surgery and can lead to various medical problems. In response to the lack of in situ retention and pro-wound healing properties of existing anti-adhesion barriers, this work reports an injectable adhesive-antifouling bifunctional hydrogel (AAB-hydrogel). This AAB-hydrogel can be constructed by "two-step" injection. The tissue adhesive hydrogel based on gallic acid-modified chitosan and aldehyde-modified dextran is prepared as the bottom hydrogel (B-hydrogel) by Schiff base reaction. The aldehyde-modified zwitterionic dextran/carboxymethyl chitosan-based hydrogel is formed on the B-hydrogel surface as the antifouling top hydrogel (T-hydrogel). The AAB-hydrogel exhibits good bilayer binding and asymmetric properties, including tissue adhesive, antifouling, and antimicrobial properties. To evaluate the anti-adhesion effect in vivo, the prepared hydrogels are injected onto the wound surface of a mouse abdominal wall abrasion-cecum defect model. Results suggest that the AAB-hydrogel has antioxidant capacity and can reduce the postoperative inflammatory response by modulating the macrophage phenotype. Moreover, the AAB-hydrogel could effectively inhibit the formation of postoperative adhesions by reducing protein deposition, and resisting fibroblast adhesions and bacteria attacking. Therefore, AAB-hydrogel is a promising candidate for the prevention of postoperative peritoneal adhesions.


Reliability and Validity of the Mandarin Version of Singing Voice Handicap Index - 10 (MSVHI-10).
The present study aims to evaluate the reliability and validity of the Mandarin version of the Singing Voice Handicap Index-10 (MSVHI-10). One hundred and fifteen singers, aged from 21 to 65, participated in this study. All the subjects completed the Mandarin version of the SVHI-10 and the Voice Handicap Index-10 (VHI-10). Other gathered information include sex, age, type of singing performance, and the accumulated years of singing. We also asked the participants to self-report the presence of singing voice complaint. Statistical analyses were performed to evaluate the validity, reliability, and the Receiver Operating Characteristic (ROC) curve of MSVHI-10. The results showed high internal consistency (Cronbach's α =0.96), with the scores of each question ranged from 0.57 to 0.90. Forty-three singers re-filled the MSVHI-10 with an interval of 12.7 ± 9.3 days (mean ± standard deviation), and the results showed a high test-retest reliability (r = 0.98, P < 0.01). The SVHI-10 scores were significantly correlated with the VHI-10 (r = 0.54-0.72, P < 0.01). ROC analysis revealed a high differentiating accuracy for distinguishing between the subjects with or without singing voice complaints, with an area under the curve (AUC) of 0.97. At the cut-off score of 21.5, the sensitivity and specificity were 85.7% and 95.9%, respectively. The Mandarin version of the SVHI-10 has been shown to be a reliable and valid instrument for evaluating the self-perception of singing voice complaints.


The borderland of multiple sclerosis and functional neurological disorder: A call for clinical research and vigilance.
Functional neurological disorders (FNDs) have attracted much attention from the neurological medical community over the last decades as new developments in neurosciences have reduced stigma around these by showing brain network dysfunctions. An overlap with other neurological conditions such as multiple sclerosis (MS) is well known by clinicians but there is a lack of clinical and fundamental research in this field to better define diagnosis and therapeutic decisions, as well as a lack of deep understanding of the underlying pathophysiology. We aimed to provide a critical commentary on the state of knowledge about the borderland between FNDs and MS. We based our commentary on a joint point of view between an FND specialist and an MS expert. A brief review of the previous literature and relevant new studies covering the overlap between FNDs and MS is presented, along with suggestions for future research directions. There are clear diagnostic criteria for both FNDs and MS and a strict application of these will help better diagnosis and prevent unnecessary treatment escalation in MS or absence of referral to multimodal therapy in FND. Better teaching of younger neurologists is needed as well as prospective research focusing on pathophysiology.


Evolution of fissures and pressure discharge of gas caused by mining of the upper protective layer of a coal seam.
The evolution of fissures and permeability associated with mining of the upper protective layer of the coal seam is crucial for pressure relief gas drainage of the underlying seam. To understand the influence of mining the upper protective layer on gas drainage within the underlying coal seam, this study utilized the M16 and M18 seams in the Qinglong Coal Mine in Guizhou. Theoretical analysis, discrete element numerical simulation, and field tests were used to characterize the evolution of fractures associated with mining of the upper protective layer and the effects of pressure relief gas drainage within the protected coal seam. The results show that mining-related stress changes controlled the development of fractures, altering the permeability values of coals. An analysis of the crack development in the coal mass caused by mining of the upper protective layer shows that during the initial stage of mining, the produced cracks exhibited a butterfly shape network. Yet, with further development of the mining, these cracks and the stress changes gradually produced an inverted butterfly shape network. According to simulations, the areas of maximum deformation via expansion in the protected coal seam were located near the open cut and the mining end line of the working face. The maximum deformation values were 29.06 and 26.68 mm, respectively, and the corresponding deformation rates were 9.37‰ and 8.61‰, which are greater than the required 3‰. The findings of this study provide a new reference for gas control in pressure relief coal seams under similar working conditions.


In vitro Evaluation of Surface Free Energy of Dentin after Treatment with Sodium Trimetaphosphate Associated or Not with Fluoride, Exposed or Not to Calcium.
It has been stated that sodium trimetaphosphate (TMP) promotes a more anionic dentin surface inducing greater calcium (Ca) and phosphate precipitation. The aim of the present study was to evaluate in vitro the surface free energy (γs) of dentin after treatment with TMP associated or not with fluoride (F), exposed or not to Ca, as well as the adsorption of TMP, F, and Ca by dentin. Bovine dentin blocks (n = 12 blocks/group) were treated with solutions containing TMP at 0, 1, 3, or 9 (w/v) followed or not by the application of Ca. These solutions were or were not associated to 1,100 ppm F. F, Ca, and TMP were determined in the solutions before and after the treatment to calculate the adsorption by dentin. To analyze the γs of dentin, the apolar (γsLW), and polar (γsAB), components were determined by contact angle measurement. Data were submitted to 2-way ANOVA followed by the Student-Newman-Keuls test (p < 0.05). TMP reduces γs of dentin and increases electron donor sites (γs-). Higher values of γs- led to higher adsorption of Ca (p < 0.001). The F/TMP association did not change γs or γsLW and reduced the values of γs-, but the adsorption of Ca was higher. There was correlation between the adsorption of TMP and γs- (Pearson's r = 0.801; p < 0.001) and F (Pearson's r = 0.871, p < 0.001). It is possible to conclude that TMP increased γs- and Ca adsorption, and reduced γs. The association with F increased the adsorption of TMP without rising γs-; however, there was higher adsorption of Ca.


Arabidopsis OXS3 family proteins repress ABA signaling through interactions with AFP1 in the regulation of ABI4 expression.
Abscisic acid (ABA) and the AP2/ERF (APETALA2/ETHYLENE-RESPONSIVE FACTOR)-type transcription factor called ABA INSENSITIVE 4 (ABI4) play pivotal roles in plant growth responses to environmental stress. An analysis of seedling development in Arabidopsis ABA hypersensitive mutants suggested that OXS3 (OXIDATIVE STRESS 3), OXS3b, O3L3 (OXS3 LIKE 3), O3L4, and O3L6 were negative regulators of ABI4 expression. We therefore characterized the roles of the OXS3 family members in ABA signaling. All the above five OXS3 proteins were found to interact with AFP1 (ABI FIVE BINDING PROTEIN 1) in yeast two hybrid assays. Seven OXS3 family members including two other members O3L1 and O3L5 were found to interact with histone H2A.X, although OXS3b, O3L3, and O3L5 showed weaker interactions. ChIP-qPCR analysis showed that the absence of some of these OXS3 family proteins was associated with increased occupancy of histone γ-H2A.X at the ABI4 promoter, which also corresponded with de-repression of ABI4 expression. Repression of ABI4 expression, however, required both AFP1 and OXS3, OXS3b or O3L6. We conclude that in the absence of stress, OXS3 family proteins regulate γ-H2A.X deposition at the ABI4 promoter and that together with AFP1, OXS3 family proteins function to prevent ABA-induced growth arrest by co-repressing ABI4 through decreased promoter occupancy of histone γ-H2A.X.


Immunomagnetic bead isolation of megakaryocytes from guinea-pig bone marrow: effect of recombinant interleukin-6 on size, ploidy and cytoplasmic fragmentation.
Guinea-pig bone marrow megakaryocytes were isolated using an antibody to platelet glycoprotein Ib and a second antibody conjugated to magnetic beads. The procedure yielded an average of 644,800 megakaryocytes from two guinea-pigs with an average viability of 83%. All of the platelet glycoprotein Ib positive cells also expressed the platelet glycoprotein IIb-IIIa complex. The size and ploidy of megakaryocytes isolated by this technique were analysed in the presence of 10 ng/ml of interleukin-6 (IL-6). Without IL-6 megakaryocyte size increased significantly after 24 h, but an even larger increase in size occurred in the presence of IL-6. The modal ploidy class was 16N with an average of 19% 2N, 2.6% 4N, 16.4% 8N, 50.8% 16N and 11.1% 32N cells as determined by flow cytometry. Measurements made by microspectrophotometry were in close agreement. After 24 h incubation there was a significant rise in the percentage of 2N and 32N cells. The ploidy distribution after 24 h with IL-6 was the same as the control. Megakaryocytes cultured in the absence of serum on collagen gels did not form pseudopods and fragment, as occurs with serum (Leven et al, 1987). Addition of IL-6 to the serum-free cultures caused megakaryocytes to form extensive proplatelet extensions. We conclude that large numbers of pure guinea-pig bone marrow megakaryocytes can be isolated by immunomagnetic bead selection, including low ploidy immature megakaryocytes. Spontaneous maturation occurred as evidenced by the increase in megakaryocyte size and ploidy. IL-6 altered megakaryocyte size and morphology but not ploidy, indicating that these different characteristics of megakaryocytes may be regulated separately.


Sensitive and quantitative determination of monocyte adherence.
A new sensitive and highly reproducible one-step ELISA is described to quantitatively determine the adherent capacity of monocytes and related cell lines. Cells were labelled with a monoclonal antibody/peroxidase conjugate which did not affect the adhesive properties of these cells. The labelled cells were allowed to adhere for 1 h and subsequently stained by the addition of substrate. The results demonstrate that there is a good correlation between the number of peroxidase-labelled adherent cells and the absorbance measured at 450 nm. Furthermore the assay permits the use of very low cell numbers since adherent cells could be measured efficiently at a level of only 100-500 cells/well. The method may be very useful in the selection of hybridomas that secrete antibodies which inhibit adherence of cells. In addition it can be applied to study the adhesive properties of any cell type, provided that appropriate monoclonal antibodies are available.