TAFs and TFIIA mediate differential utilization of the tandem Adh promoters.
The D. melanogaster alcohol dehydrogenase (Adh) gene is transcribed from two tandem promoters that are differentially utilized at various stages during development. To determine the mechanism of promoter selectivity, we have analyzed the activity of the Adh promoters both in vitro and in transfected cells. We found that selective promoter utilization is controlled by distinct initiator elements. Reconstitution of Adh transcription with purified components requires a specific TBP-TAF complex that, in concert with TFIIA, directs differential Adh promoter transcription. Fractionation of this TBP-TAF complex reveals that TAFII150 is required for discrimination between the proximal and distal promoters. We propose a mechanism for regulating differential promoter utilization during Drosophila development that involves the recognition of specific initiator elements by TAFs in the TFIID complex.


Day-care, early common infections and childhood acute leukaemia: a multicentre French case-control study.
We conducted a case-control study to investigate the role of early infections in the aetiology of childhood acute leukaemias. The study included 280 incident cases (240 acute lymphoblastic leukaemia and 40 acute non-lymphoblastic leukaemia) and 288 hospital controls, frequency matched by age, gender, hospital, catchment area of the hospital and ethnic origin. Data were obtained from standardised face-to-face interviews of the mothers. The interviews included questions on early common infections, day-care attendance, breast-feeding, birth order and infantile diseases. Odds ratios were estimated using an unconditional regression model including the stratification variables, parental socio-economic status and perinatal characteristics. Birth order was not associated with childhood leukaemia (acute lymphoblastic or acute non-lymphoblastic). A statistically-significant inverse association was observed between childhood leukaemia and day-care attendance (odds ratio=0.6, 95% Confidence Interval=(0.4-1.0)), repeated early common infections (> or = 4 per year before age two, odds ratio=0.6 (0.4-1.0)), surgical procedures for ear-nose-throat infections before age two (odds ratio=0.5 (0.2-1.0)) and prolonged breast-feeding (> or = 6 months, odds ratio=0.5 (0.2-1.0)). In the multivariate model including day-care attendance, early common infections and breast-feeding, results concerning breast-feeding remained unchanged. A statistically significant interaction between day-care attendance and repeated early common infections was observed. When the interaction was taken into account, the simple effects of day-care and early common infections disappeared (odds ratio=1.1 (0.5-2.3) and odds ratio=0.8 (0.5-1.3), respectively) while the joint effect of day-care attendance and early common infections was negatively associated with childhood leukaemia (odds ratio=0.3 (0.1-0.8)). All the above associations were observed both for acute lymphoblastic leukaemia and acute non-lymphoblastic leukaemia. Our results support Greaves' hypothesis, even though they are not specific of common leukaemia.


Interleukin-17: the missing link between T-cell accumulation and effector cell actions in rheumatoid arthritis?
The prominence of T cells and monocyte/macrophages in rheumatoid synovium suggests T cells may localize and amplify the effector functions of monocyte/macrophages in rheumatoid disease. However, while T cells are abundant in rheumatoid joints, classic T-cell derived cytokines are scarce, especially when compared to the levels of monokines IL-1 beta and TNF-alpha. For this reason, it has been speculated that monocyte/macrophages may act independently of T cells in rheumatoid disease and that the role of T cells may be more or less irrelevant to core disease mechanisms. The question of T-cell influence requires re-evaluation in light of the characterization of IL-17, a T-cell derived cytokine that is abundant in rheumatoid synovium and synovial fluid. IL-17 has a number of pro-inflammatory effects, both directly and through amplification of the effects of IL-1 beta and TNF-alpha. IL-17 is able to induce expression of pro-inflammatory cytokines and stimulate release of eicosanoids by monocytes and synoviocytes. Furthermore, IL-17 has been implicated in the pathogenesis of inflammatory bone and joint damage through induction of matrix metalloproteinases and osteoclasts, as well as inhibition of proteoglycan synthesis. In animal models of arthritis, intra-articular injection of IL-17 results in joint inflammation and damage. The recognition of IL-17 as a pro-inflammatory T cell derived cytokine, and its abundance within rheumatoid joints, provides the strongest candidate mechanism to date through which T cells can capture and localize macrophage effector functions in rheumatoid arthritis. As such, IL-17 warrants consideration for its potential as a therapeutic target in rheumatoid arthritis.


A functional MRI study of movement-associated cortical changes in patients with Devic's neuromyelitis optica.
Movement-associated cortical changes have been shown in several neurological conditions and were found to be associated to the extent of brain and cord damage. Devic's neuromyelitis optica (DNO) is characterized by a severe involvement of the cord and optic nerve, with sparing of the brain. To assess the actual role of cord pathology on the pattern of movement-associated cortical recruitment, we obtained functional magnetic resonance imaging (fMRI) from patients with DNO and investigated whether the extent of brain activation is correlated with the extent of cervical cord damage. We studied 10 right-handed DNO patients and 15 sex- and age-matched healthy controls. The MRI assessment consisted of the following: (a) fMRI during repetitive flexion extension of the last four fingers of the right and left hand, (b) brain and cervical cord conventional MRI, and (c) cervical cord magnetization transfer (MT) MRI. Compared to controls and for both tasks, DNO patients had an increased recruitment of several regions of the sensorimotor network (primary sensorimotor cortex, postcentral gyrus, middle frontal gyrus, rolandic operculum, secondary sensorimotor cortex, precuneus, and cerebellum) and of several other regions mainly in the temporal and occipital lobes, such as MT/V5, the fusiform gyrus, the cuneus, and the parahippocampal gyrus. For both tasks, strong correlations (r values ranging from -0.76 to -0.85) were found between relative activations of cortical sensorimotor areas and the severity of cervical cord damage. This study shows an abnormal pattern of movement-associated cortical activations in patients with DNO, which extends beyond the 'classical' sensorimotor network and also involves visual areas devoted to motion processing. The correlation found between fMRI changes and the extent of cord damage suggests that such functional cortical changes might have an adaptive role in limiting the clinical outcome of DNO structural pathology.


Job strain and resting heart rate: a cross-sectional study in a Swedish random working sample.
Numerous studies have reported an association between stressing work conditions and cardiovascular disease. However, more evidence is needed, and the etiological mechanisms are unknown. Elevated resting heart rate has emerged as a possible risk factor for cardiovascular disease, but little is known about the relation to work-related stress. This study therefore investigated the association between job strain, job control, and job demands and resting heart rate. We conducted a cross-sectional survey of randomly selected men and women in Västra Götalandsregionen, Sweden (West county of Sweden) (n = 1552). Information about job strain, job demands, job control, heart rate and covariates was collected during the period 2001-2004 as part of the INTERGENE/ADONIX research project. Six different linear regression models were used with adjustments for gender, age, BMI, smoking, education, and physical activity in the fully adjusted model. Job strain was operationalized as the log-transformed ratio of job demands over job control in the statistical analyses. No associations were seen between resting heart rate and job demands. Job strain was associated with elevated resting heart rate in the unadjusted model (linear regression coefficient 1.26, 95 % CI 0.14 to 2.38), but not in any of the extended models. Low job control was associated with elevated resting heart rate after adjustments for gender, age, BMI, and smoking (linear regression coefficient -0.18, 95 % CI -0.30 to -0.02). However, there were no significant associations in the fully adjusted model. Low job control and job strain, but not job demands, were associated with elevated resting heart rate. However, the observed associations were modest and may be explained by confounding effects.


The burden of skin and subcutaneous diseases: findings from the global burden of disease study 2019.
The small number of existing integrative studies on the global distribution and burden of all types of skin and subcutaneous diseases hinders relevant comparisons. This study aimed to determine the latest distribution, epidemiological differences, and factors potentially influencing each skin and subcutaneous disease and the policy implications. Data on the skin and subcutaneous diseases were obtained from the Global Burden of Disease Study 2019. The incidence, disability-adjusted life years (DALYs), and deaths due to skin and subcutaneous diseases in 204 countries and regions from 1990 to 2019 were analyzed and stratified by sex, age, geographical location, and sociodemographic index (SDI). The annual age-standardized rate of change in the incidence was obtained to evaluate temporal trends. Of 4,859,267,654 (95% uncertainty interval [UI], 4,680,693,440-5,060,498,767) new skin and subcutaneous disease cases that were identified, most were fungal (34.0%) and bacterial (23.0%) skin diseases, which accounted for 98,522 (95% UI 75,116-123,949) deaths. The burden of skin and subcutaneous diseases measured in DALYs was 42,883,695.48 (95%UI, 28,626,691.71-63,438,210.22) in 2019, 5.26% of which were years of life lost, and 94.74% of which were years lived with disability. The highest number of new cases and deaths from skin and subcutaneous diseases was in South Asia. Globally, most new cases were in the 0-4-year age group, with skin and subcutaneous disease incidence slightly higher in men than in women. Fungal infections are major contributors to skin and subcutaneous diseases worldwide. Low-middle SDI states had the highest burden of skin and subcutaneous diseases, and this burden has increased globally. Targeted and effective management strategies based on the distribution characteristics of each country are, thus, required to reduce the burden of skin and subcutaneous diseases.


Object-based attention occurs regardless of object awareness.
In this study, we investigated whether awareness of objects is necessary for object-based guidance of attention. We used the two-rectangle method (Egly, Driver, & Rafal, 1994) to probe object-based attention and adopted the continuous flash suppression technique (Tsuchiya & Koch, 2005) to control for the visibility of the two rectangles. Our results show that object-based attention, as indexed by the same-object advantage--faster response to a target within a cued object than within a noncued object--was obtained regardless of participants' awareness of the objects. This study provides the first evidence of object-based attention under unconscious conditions by showing that the selection unit of attention can be at an object level even when these objects are invisible--a level higher than the previous evidence for a subliminally cued location. We suggest that object-based attentional guidance plays a fundamental role of binding features in both the conscious and unconscious mind.


Fenestration of the supraclinoid internal carotid artery associated with aneurysm and ischemic stroke.
Fenestration of the ICA is extremely rare, and the most common associated vascular abnormality is cerebral aneurysm. The relationship between fenestration and ischemic stroke is unknown. We present a case of a young adult with SAH resulting from a ruptured aneurysm, associated with the bilateral fenestrated supraclinoid ICAs. This case is unusual because of a history of 2 ischemic strokes and the concomitant finding of other vascular abnormalities. Besides associated with aneurysm, ischemic stroke also indicates that fenestration may be a risk factor for thrombus or embolus formation.


Neuroprotection--rationale for pharmacological modulation of Na(+)-channels.
The primary factor detrimental to neurons in neurological disorders associated with deficient oxygen supply or mitochondrial dysfunction is insufficient ATP production relative to their requirement. As a large part of the energy consumed by brain cells is used for maintenance of the Na+ gradient across the cellular membrane, reduction of energy demand by down-modulation of voltage-gated Na(+)-channels is a rational strategy for neuroprotection. In addition, preservation of the inward Na+ gradient may be beneficial because it is an essential driving force for vital ion exchanges and transport mechanisms such as Ca2+ homeostasis and neurotransmitter uptake.


The activity of Balbiani rings 1 and 2 in salivary glands of Chironomus tentans larvae under different modes of development and after pilocarpine treatment.
The activity of the Balbiani rings 1 and 2 (BR1 and BR2) in the salivary gland was followed during development of fourth instar larvae of Chironomus tentans under different modes of development, with or without a previous pilocarpine treatment. The activity was determined in parallel by two different methods, by incorporation of [3H]uridine into BR-RNA (75 S) and by morphometry of BR1 and of BR2. In glands of untreated larvae BR2 does not change dramatically except for a depression of activity during oligopause (resting phase). BR1 is completely inactive during this phase but exhibits a pronounced activity maximum in the middle of the prepupal period, in subitaneously developing (i.e., uninterrupted) as well as in postoligopause cultures. After pilocarpine treatment the activity of BR2 (rather than of BR1) is generally increased. The extent of this stimulation, however, is strongly development dependent. A most striking activity difference is observed in postoligopause between animals of stage 5 and of stage 6. The relationship between BR2 activity and degree of emptying of the salivary gland lumen was investigated. A model is proposed in which BR2 activity is conceived as being regulated by two parameters: by the degree of filling of the gland lumen and by the stage and mode of development of the larva.


[Post-Intensive Care Unit mortality and related prognostic factors in a cohort of critically ill patients with multi-organ dysfunction].
To assess the post-Intensive Care Unit (ICU) mortality (in-hospital and one year after hospital discharge) and the associated factors. Cohort design in medical-surgical patients with multi-organ dysfunction syndrome (MODS) during the first 24h of admission to ICU. We recorded the following data: personal background, functional general situation, general information about admission to ICU, hospital stay and contact by phone after one year of hospital discharge. We registered mortality at the follow-up at anytime. Cox regression was performed to evaluate mortality factors. Five hundred and forty five patients were recruited. During the study period 256 patients (52.9%) died; out of them 29.5% in ICU; 14.8% of 384 patients transferred to the ward died. Of 327 discharged patients, 266 (81.3%) were contacted; 14.3% of those had died. In-hospital death-related factors were age (odds ratio [OR] 1.04; 95% confidence interval [95% CI] 1.02-1.06; P<.01) and a decreased functional general status (OR 1.7; 95% CI 1.1-2.9; P<.05). Post-hospitalisation mortality-related variables were: diminished functional general status (OR 2.42; 95% CI 1.23-4.75; P<.01) and readmission after discharge from hospital (1.45 OR; 95% CI 1.19-1.76; P<.001). Patients admitted for a medical-surgical MODS presented a mortality of 52.9% within one year. The factors influencing hospital mortality are age and a generally diminished functional status, both being not modifiable factors. After discharge, the decreased general functional status remained central along with the re-hospitalisation.


Sense of mastery differences between working-age Swedish- and Finnish-speaking Finns: a population-based study.
To examine the probability of a high sense of mastery in a population-representative sample of working-age people and to study the differences in mastery between Finnish-speaking and Swedish-speaking Finns in particular. The data originates from the Western Finland Mental Health Surveys (2008-2014). Associations between sense of mastery and language groups were analyzed with logistic regressions. Swedish-speaking Finns have a higher sense of mastery and the association is mediated by social support. Moreover, a difference in a high sense of mastery is found between Swedish- and Finnish-speaking married women that are outside the labor market. Our findings imply that Finnish-speaking women that are outside the labor market, e.g. on maternity leave or taking care of the household, should be recognized in health and social care services as a group that can benefit from additional support.


Causal and predictive-value judgments, but not predictions, are based on cue-outcome contingency.
In three experiments, we show that people respond differently when they make predictions as opposed to when they are asked to estimate the causal or the predictive value of cues: Their response to each of those three questions is based on different sets of information. More specifically, we show that prediction judgments depend on the probability of the outcome given the cue, whereas causal and predictive-value judgments depend on the cue-outcome contingency. Although these results might seem problematic for most associative models in their present form, they can be explained by explicitly assuming the existence of postacquisition processes that modulate participants' responses in a flexible way.


Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post-hoc analysis of the ATHOS-3 clinical trial.
High dose vasopressors portend poor outcome in vasodilatory shock. We aimed to evaluate the impact of baseline vasopressor dose on outcomes in patients treated with angiotensin II (AT II). Exploratory post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial data. The ATHOS-3 trial randomized 321 patients with vasodilatory shock, who remained hypotensive (mean arterial pressure of 55-70 mmHg) despite receiving standard of care vasopressor support at a norepinephrine-equivalent dose (NED) > 0.2 µg/kg/min, to receive AT II or placebo, both in addition to standard of care vasopressors. Patients were grouped into low (≤ 0.25 µg/kg/min; n = 104) or high (> 0.25 µg/kg/min; n = 217) NED at the time of study drug initiation. The primary outcome was the difference in 28-day survival between the AT II and placebo subgroups in those with a baseline NED ≤ 0.25 µg/kg/min at the time of study drug initiation. Of 321 patients, the median baseline NED in the low-NED subgroup was similar in the AT II (n = 56) and placebo (n = 48) groups (median of each arm 0.21 µg/kg/min, p = 0.45). In the high-NED subgroup, the median baseline NEDs were also similar (0.47 µg/kg/min AT II group, n = 107 vs. 0.45 µg/kg/min placebo group, n = 110, p = 0.75). After adjusting for severity of illness, those randomized to AT II in the low-NED subgroup were half as likely to die at 28-days compared to placebo (HR 0.509; 95% CI 0.274-0.945, p = 0.03). No differences in 28-day survival between AT II and placebo groups were found in the high-NED subgroup (HR 0.933; 95% CI 0.644-1.350, p = 0.71). Serious adverse events were less frequent in the low-NED AT II subgroup compared to the placebo low-NED subgroup, though differences were not statistically significant, and were comparable in the high-NED subgroups. This exploratory post-hoc analysis of phase 3 clinical trial data suggests a potential benefit of AT II introduction at lower doses of other vasopressor agents. These data may inform design of a prospective trial. The ATHOS-3 trial was registered in the clinicaltrials.gov repository (no. NCT02338843). Registered 14 January 2015.


What limits photosynthesis? Identifying the thermodynamic constraints of the terrestrial biosphere within the Earth system.
Photosynthesis converts sunlight into the chemical free energy that feeds the Earth's biosphere, yet at levels much lower than what thermodynamics would allow for. I propose here that photosynthesis is nevertheless thermodynamically limited, but this limit acts indirectly on the material exchange. I substantiate this proposition for the photosynthetic activity of terrestrial ecosystems, which are notably more productive than the marine biosphere. The material exchange for terrestrial photosynthesis involves water and carbon dioxide, which I evaluate using global observation-based datasets of radiation, photosynthesis, precipitation and evaporation. I first calculate the conversion efficiency of photosynthesis in terrestrial ecosystems and its climatological variation, with a median efficiency of 0.77% (n = 13,274). The rates tightly correlate with evaporation on land (r2 = 0.87), which demonstrates the importance of the coupling of photosynthesis to material exchange. I then infer evaporation from the maximum material exchange between the surface and the atmosphere that is thermodynamically possible using datasets of solar radiation and precipitation. This inferred rate closely correlates with the observation-based land evaporation dataset (r2 = 0.84). When this rate is converted back into photosynthetic activity, the resulting patterns correlate highly with the observation-based dataset (r2 = 0.66). This supports the interpretation that it is not energy directly that limits terrestrial photosynthesis, but rather the material exchange that is driven by sunlight. This interpretation can explain the very low, observed conversion efficiency of photosynthesis in terrestrial ecosystems as well as its spatial variations. More generally, this implies that one needs to take the necessary material flows and exchanges associated with life into account to understand the thermodynamics of life. This, ultimately, requires a perspective that links the activity of the biosphere to the thermodynamic constraints of transport processes in the Earth system.


Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates.
Containment of highly lethal Ebola virus outbreaks poses a serious public health challenge. Although an experimental vaccine has successfully protected non-human primates against disease, more than six months was required to complete the immunizations, making it impractical to limit an acute epidemic. Here, we report the development of accelerated vaccination against Ebola virus in non-human primates. The antibody response to immunization with an adenoviral (ADV) vector encoding the Ebola glycoprotein (GP) was induced more rapidly than with DNA priming and ADV boosting, but it was of lower magnitude. To determine whether this earlier immune response could nonetheless protect against disease, cynomolgus macaques were challenged with Ebola virus after vaccination with ADV-GP and nucleoprotein (NP) vectors. Protection was highly effective and correlated with the generation of Ebola-specific CD8(+) T-cell and antibody responses. Even when animals were immunized once with ADV-GP/NP and challenged 28 days later, they remained resistant to challenge with either low or high doses of virus. This accelerated vaccine provides an intervention that may help to limit the epidemic spread of Ebola, and is applicable to other viruses.


[Prevention of cytomegalovirus infection: preemptive therapy versus universal prophylaxis].
Despite the advances made in the diagnosis and treatment of cytomegalovirus (CMV) infection, this pathogen continues to cause substantial morbidity in solid organ transplant (SOT) recipients. The two main strategies for the prevention of CMV disease are universal prophylaxis and preemptive therapy. Several meta-analyses have found that both strategies are effective in the prevention of CMV disease in SOT recipients compared with placebo, each with its own advantages and disadvantages. Nevertheless, few studies have compared the two approaches to CMV disease in SOT recipients. The present article provides a review of the indications of each of these strategies and the main studies on which they are based.


Expression of a novel dual-functional polypeptide and its pharmacological action research.
To develop a dual-functional medicine for hypoglycemic and anti-thrombus. The long-acting glucagon like peptide-1 (5×GLP-1) and nattokinase (NK) were cloned by SOE PCR and gained the GLP-1 and NK fusion polypeptide after transformed into E. coli. Use of mice models for the hypoglycemic and anti-thrombus activity of the fusion polypeptide. Balb/C mice were given the carrageenan by intraperitoneal injection to induce tail thrombus models. Type 2 diabetes mellitus mice model was used to research the hypoglycemic function of the fusion polypeptide. Results showed that the fusion polypeptide could significantly prevent thrombus formation after oral administration. Continuous administration for 15 days, fasting blood glucose levels of the experimental group decreased to nearly normal levels. The present study investigated the expression, purification and functional activity of the rolGLP-1 and NK fusion polypeptide, which provided a foundation for further studying the detailed pharmaceutical mechanism and drug development.


TRIM58 inactivates p53/p21 to promote chemoresistance via ubiquitination of DDX3 in breast cancer.
Chemotherapy resistance is that the most important reason behind of carcinoma treatment failure but the underlying molecular mechanisms are unclear. Members of the tripartite motifcontaining protein (TRIM) family play crucial roles in the carcinogenesis and development of resistance against chemotherapy. Herein, we first confirmed that TRIM58 is highly expressed in triple-negative breast cancer tissues and drug-resistant MCF7/ADR cells. Furthermore, TRIM58 knockdown resulted in increased sensitivity of MCF7/ADR cells toward doxorubicin in vitro and in vivo. In contrast, TRIM58 overexpression in breast cancer cells increased doxorubicin resistance. TRIM58 was found to interact with DDX3, a protein recently reported to modulate resistance against chemotherapy. We found that TRIM58 negatively regulates DDX3 expression downstream of the P53/P21 pathway, and that DDX3 is degraded by TRIM58-mediated ubiquitination. Knockdown of DDX3 reversed doxorubicin chemotherapy sensitivity induced by TRIM58 knockdown via the P53/P21 pathway.Our study reveals that TRIM58 mediates a novel mechanism underlying the development of resistance against chemotherapy in breast cancer and provides potential targets for developing novel therapeutic targets for breast cancer.


Association of chemokine gene variants with end stage renal disease in North Indian population.
The progression rate of chronic kidney disease (CKD) to its end-stage renal disease (ESRD), and the development and severity of various complications, are indirectly influenced by genetic and epigenetic factors. Chemokines are small inducible pro-inflammatory cytokines, which are implicated in many biological processes like migration of leukocytes, angiogenesis, tumor growth and metastasis. We tested association of four single nucleotide polymorphisms (SNPs) viz. CCL2I/D, CCL2A2518G, CXCL12G801A and CXCR2(+1208)C/T among individuals with ESRD (end stage renal disease) and normal healthy controls from North Indian population. CCL2I/D, CCL2A2518G, CXCL12G801A and CXCR2(+1208)C/T were genotyped in blood samples of hospital-based case-control study comprising of 200 ESRD cases and 200 healthy controls using Restriction Fragment Length Polymorphism (RFLP) and ARMS (Amplification Refractory Mutation Specific) PCR methodology. A significant association was found in CXCL12G801A with ESRD risk. In case of CXCL12G801A polymorphism heterozygous (GA) genotype showed significant risk (p=0.039; OR=1.55) whereas A allele carrier (GA+AA) also exhibited risk with ESRD (p=0.045, OR=1.59). In CXCR2(+1208)C/T polymorphism, the heterozygous genotype (CT) showed significant risk for ESRD (p=0.028; OR=1.65) and combination of CT+TT demonstrated significant high risk for ESRD (p=0.036; OR=1.52). In case of CCL2I/D, the variant genotype (D/D) showed reduced risk for ESRD patients. Upon analyzing the gene-gene interaction between CXCR2 and CXCL12, the combination (CT-GA) showed 2.65 fold risk for ESRD (p=0.018). Our results indicated that polymorphism in CXCL12G801A and CXCR2(+1208)C/T showed high risk for ESRD in North Indian population. However, CCL2I/D showed reduced risk and CCL2A2518G exhibited no association. Study with large sample size and diverse ethnicity is required to validate these observations.


Hyperreactio luteinalis in a normal pregnancy: sonographic and MRI findings.
A case of hyperreactio luteinalis in an otherwise normal pregnancy is reported. Ascites was present, but no peritoneal implants or adenopathy were seen. Findings that would have suggested the correct diagnosis are the symmetrical and bilateral pattern of the mass, as well as the rather uniform size of the loculi, which were 1 to 3 cm in diameter.


Aging in Rothmund-Thomson syndrome and related RECQL4 genetic disorders.
Rothmund-Thomson Syndrome (RTS) is a rare autosomal recessive disease which manifests several clinical features of accelerated aging. These findings include atrophic skin and pigment changes, alopecia, osteopenia, cataracts, and an increased incidence of cancer for patients carrying RECQL4 germline mutations. Mutations in RECQL4 are responsible for the majority of cases of RTS. RECQL4 belongs to RECQ DNA helicase family which has been shown to participate in many aspects of DNA metabolism. In the past several years, accumulated evidence indicates that RECQL4 is important not only in cancer development but also in the aging process. In this review, based on recent research data, we summarize the common aging findings in RTS patients and propose possible mechanisms to explain the aging features in these patients.


Meeting report for Odd Pols 2012.
The Eighth International Biennial Conference on RNA polymerases I and III (the 'Odd Pols') was held June 7-11, 2012 at The Airlie Center in Warrenton Virginia, USA. It was sponsored by the Universite Laval and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, and organized by Rich Maraia and Tom Moss. The meeting honored the memory of Pierre Thuriaux (Jan 1, 1950-March 18, 2012) and David Schneider reminisced on the important accomplishments his mentor Masayasu Nomura (1927-2011). The goal of the conference was to bring together the world's experts on RNA polymerase I and RNA polymerase III to highlight and share their latest results and varied experimental approaches. The meeting drew attendees from twelve countries and most contributed through oral and poster presentations. The talks were organized into several sessions subdivided into 10 distinct topics. The keynote speaker, Ian Willis, opened the meeting with his presentation entitled "New Regulators of Signaling to Odd Pols" and the closing presentation was given by Patrick Cramer with his presentation "Conservation of the RNA polymerase I, II and III transcription initiation machineries". Here we present some of the highlights from the meeting using summaries provided by the participants.


Effect of a reminder video using a mobile phone on the retention of CPR and AED skills in lay responders.
Skills related to cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use by lay responders decay rapidly after training, and efforts are required to maintain competence among trainees. We examined whether repeated viewing of a reminder video on a mobile phone would be an effective means of maintaining CPR and AED skills in lay responders. In a single-blind case-control study, 75 male students received training in CPR and AED use. They were allocated either to the control or to the video-reminded group, who received a memory card containing a video clip about CPR and AED use for their mobile phone, which they were repeatedly encouraged to watch by SMS text message. CPR and AED skills were assessed in scenario format by examiners immediately and 3 months after initial training. Three months after initial training, the video-reminded group showed more accurate airway opening (P<0.001), breathing check (P<0.001), first rescue breathing (P=0.004), hand positioning (P=0.004), AED electrode positioning (P<0.001), pre-shock safety check (P<0.001), defibrillation within 90s (P=0.010), and resuming CPR after defibrillation (P<0.001) than controls. They also showed significantly higher self-assessed CPR confidence scores and increased willingness to perform bystander CPR in cardiac arrest than the controls at 3 months (P<0.001, P=0.024, respectively). Repeated viewing of a reminder video clip on a mobile phone increases retention of CPR and AED skills in lay responders.


Evidence for epistatic gene interactions between growth factor genes in stroke outcome.
Growth factors are thought to modulate neurological function in stroke recovery through effects in angiogenesis, neurogenesis, and neuroprotection. We tested the association of variants in the brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) genes, and epistatic interactions between them, with functional outcome in a sample of 546 stroke patients. While none of the tested genes was independently associated with stroke outcome, two significant gene-gene interaction models were identified. One model combined one BDNF and three FGF2 markers, with a global odds ratio (OR) (95% confidence interval [CI]) of 4.15 [2.86-6.04]. The second model included one FGF2 and two VEGFA markers with a global OR [95% CI] = 2.54 [1.76-3.67]. The results provide evidence for gene interactions in stroke outcome, highlighting the complexity of the recovery mechanisms after a stroke event.


Free radicals and cardioplegia. Free radical scavengers improve postischemic function of rat myocardium.
Oxygen-derived free radicals, such as the superoxide (O2-) anion, hydrogen peroxide (H2O2) and the hydroxyl (OH.) radical, may be involved in exacerbating myocardial injury during reoxygenation of ischemic tissue. The naturally occurring antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), prevent the formation of the cytotoxic OH. radical during physiological conditions but may not be able to cope with the free radical generation that follows ischemia and reperfusion. We have used the isolated perfused working rat heart model of cardiopulmonary bypass and ischemic arrest to assess whether exogenous addition of SOD (20 IU/ml) and CAT (100 IU/ml) during ischemia and/or reperfusion can improve postischemic recovery of function following normothermic or hypothermic global ischemic arrest induced by St. Thomas' Hospital cardioplegic solution. Under conditions of normothermia, the addition of SOD alone or CAT alone to both the cardioplegic solution (CS) and the reperfusion solution (RS) had no effect on postischemic recovery (after 20-min working reperfusion) of aortic flow (27.9 +/- 2.7% and 16.1 +/- 6.3%, respectively) when compared with the nontreated control value of 28.1 +/- 3.7%. However, recovery was improved when SOD plus CAT were added to the CS alone (39.3 +/- 8.7%) and was significantly improved when they were added either to both the CS and the RS (48.4 +/- 6.0%; P = less than 0.02) or to the RS alone (51.3 +/- 3.7%; P = less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Genotoxicity of triasulfuron in the wing spot test of Drosophila melanogaster is modulated by winter wheat seedlings.
Triasulfuron (TS) is a widely used sulfonylurea herbicide which inhibits the acetolactate synthase in broad-leaf weeds and in some wheat crop grasses (Triticum aestivum L.). Residues can be found in soil and superficial water with high toxicity to primary producers. In cereals, TS metabolism depends on cytochromes P450 (CYPs), the age of seedlings and the interaction with compounds. The genotoxicity of TS was demonstrated in the wing spot test of Drosophila melanogaster, an in vivo assay based on the loss of heterozygosity of the mwh and flr markers in the wing imaginal disk cells of larvae fed with chemical agents. Chronic treatments with analytical grade TS, commercial formulation TS (Amber) 75WG) (0.5mg/mL) and commercial formulation bentazon (Basagran) 480) (0.24mg/mL) were performed with three-day-old larvae of the standard (ST) and the high bioactivation (HB) crosses with regulated and high constitutive levels of CYPs, respectively. To demonstrate the effect of winter wheat metabolism on TS genotoxicity, T. aestivum L. seedlings were immersed for 4h in these herbicides, and aqueous extracts (AEs) of the roots were prepared to expose the larvae. TS and Amber 75WG produced similar genotoxic effects in both crosses. Wheat metabolism modulated the genotoxicity because the AEs yielded statistically significant lower spot frequencies in the HB cross than in the ST cross. Differences between the two crosses of the wing spot test in D. melanogaster must be related to CYPs levels. Basagran 480 was genotoxic only in the HB cross, and wheat metabolism did not modulate its genotoxicity.


Evaluation of offline sampling for atmospheric C3-C11 non-methane hydrocarbons.
The concentration variation of C3-C11 non-methane hydrocarbons (NMHCs) collected in several types of commercial flexible bags and adsorption tubes was systematically investigated using a gas chromatography-flame ionization detector (GC-FID) system. The percentage loss of each NMHC in the polyvinyl fluoride (PVF) bags was less than 5% during a 7-hr storage period; significant NMHCs loss was detected in aluminum foil composite film and fluorinated ethylene propylene bags. The thermal desorption efficiency of NMHCs for adsorption tubes filled Carbopack B and Carboxen1000 sorbents was greater than 95% at 300℃, and the loss of NMHCs in the adsorption tubes during 20-days storage at 4℃ was less than 8%. The thermal desorption efficiency for C11 NMHCs in the adsorption tube filled with Carbograph 1 and Carbosieve SⅢ absorbents was less than 40% at 300℃, and pyrolysis of the absorbents at 330℃ interfered significantly with the measurements of some alkenes. The loss of alkenes was significant when NMHCs were sampled by cryo-enrichment at -90℃ in the presence of O3 for the online NMHC measurements, and negligible for enrichment using adsorption tubes at 25℃. Although O3 scrubbers have been widely used to eliminate the influence of O3 on NMHC measurements, the loss of NMHCs with carbon numbers greater than 8 was more than 10%. Therefore, PVF bags and adsorption tubes filled Carbopack B and Carboxen1000 sorbents were recommended for the sampling of atmospheric NMHCs.


Electrical stimulation of rhesus monkey nucleus reticularis gigantocellularis. I. Characteristics of evoked head movements.
The nucleus reticularis gigantocellularis (NRG) receives monosynaptic input from the superior colliculus (SC) and projects directly to neck motor neuron pools. Neurons in NRG are well situated to play a critical role in transforming SC signals into head movement commands. A previous study of movements evoked by NRG stimulation in the primate reported a variety of ipsilateral and contralateral head movements with horizontal, vertical and torsional components. In addition to head movements, it was reported that NRG stimulation could evoke movements of the pinnae, face, upper torso, and co-contraction of neck muscles. In this report, the role of the rhesus monkey NRG in head movement control was investigated using electrical stimulation of the rostral portion of the NRG. The goal was to characterize head movements evoked by NRG stimulation, describe the effects of altering stimulation parameters, and assess the relative movements of the eyes and head. Results indicate that electrical stimulation in the rostral portion of the NRG of the primate can consistently evoke ipsilateral head rotations in the horizontal plane. Head movement amplitude and peak velocity depend upon stimulation parameters (primarily frequency and duration of stimulation trains). During stimulation-induced head movements the eyes counter-rotate (presumably a result of the vestibulo-ocular reflex: VOR). At 46 stimulation sites from two subjects the average gain of this counter-rotation was -0.38 (+/-0.18). After the end of the stimulation train the head generally continued to move. During this epoch, after electrical stimulation ceased, VOR gain remained at this reduced level. In addition, VOR gain was similarly low when electrical stimulation was carried out during active fixation of a visual target. These data extend existing descriptions of head movements evoked by electrical stimulation of the NRG, and add to the understanding of the role of this structure in producing head movements.


How do supervising doctors construe the medical student in clinical training?
Basing the prediction of student performance in medical school on intellective-cognitive abilities alone has proved to be more pertinent to academic achievement than to clinical practice. A major obstacle to the development of adequate measures has been the elusive nature of requirements for successful clinical performance. The present study aimed at defining the relevant variables through an analysis of the concept of the medical student held by supervising doctors. With the aid of a methodology derived from cognitive-social psychology, the components of how training doctors of a large medical school evaluate their students were first explicated in structured interviews. In a second phase of the research, 18 supervisors in five major clinical departments rated their student-supervisees on 15 obtained traits. Findings of trait correlations with an overall evaluation, as well as Guttman's 'Smallest Space Analysis' (1968), indicated a clear priority of cognitive-motivational traits in supervisors' judgements and reduced relevance of personal and interpersonal variables. Certain inconsistencies between avowed ideology of medical training and actual supervising practice could be detected.


Targeted badger removal and the subsequent risk of bovine tuberculosis in cattle herds in county Laois, Ireland.
We investigated the impact of targeted removal of badgers on the subsequent bovine tuberculosis (BTB) risk in cattle herds in county Laois, Ireland. The study period was 1989-2005. For each of 122 targeted badger-removal licenses (permit to remove badgers in the proximity of cattle herds undergoing a serious BTB episode), the herd number (index herd) for which the license was given was obtained. The herds in the proximity of the index herd were identified from another database. The main "exposure" in our study was the geographical location of herds relative to the area in which targeted badger removal was conducted. We categorized herds into five different exposure groups: herds were classified as non-exposed and denoted as group 0 (reference group) if they were located 500 m or more from the edge of any parcel of land of the index herd; group 1, was the index herds, group 2 the immediate (contiguous) neighbors of the index herd, group 3 herds were not immediate neighbors but within 150 m and group 4 herds were between 150 m and 500 m distance from the edge of any parcel of land of the index herd, respectively. We conducted a survival analysis (allowing multiple failures per herd) to compare the hazard of having a BTB episode in any of the four groups of exposed herds vs. the hazard in herds in the reference group. We controlled for other known risk factors as well taking into account a temporal component. Our analysis showed that the hazard ratio for the index herds (group 1) were non-significantly increased, indicating that there was no difference in the hazard of failing a BTB test (after the targeted badger removal was conducted) between index herds and reference herds. For the rest of the herds farther away from badger removal activities the hazards were lower than herds in areas not under badger removal. The hazard in the reference group decreased over the study period.


Characterization of reticulocyte release factor.
The release factor (RF) of reticulocytes has been purified to greater than 75% homogeneity. The RF has a native molecular weight of 105,000 and subunit molecular weight of 56,500. The RF protein will bind to reticulocyte ribosomes in response to UAAA, UAGA, or UGAA and therefore participates in codon recognition. The fraction possess a ribosome-dependent GTPase activity. The RF is stimulated in its activity by a second protein fraction.


Introduction to Functional MR Imaging.
During the past decade, functional MR imaging has rapidly moved from the research environment into clinical practice. Preoperative functional MR imaging is now standard clinical practice not only in major academic institutions, but also in community neurosurgical and neuroradiologic practices. The clinical use of functional MR imaging will only increase in the years to come. Application of functional MR imaging (including resting-state functional MR imaging) to the context of neuropsychiatric diseases is likely to continue to advance.


Emergency department management of nerve agent exposure.
Nerve agents are toxic chemicals developed for use by the military, but used by terrorists against civilian populations. As threats of terrorism increase, it is possible that health care providers will be confronted with multiple victims of nerve agent exposure. Nerve agents are highly toxic forms of organophosphate poisons that potentially could cause harm to anyone who comes in contact. Emergency personnel need to be familiar with the agents, know how to prepare for encountering and treating victims, and know how to protect all people involved from further poisoning.


Iatrogenic radial nerve palsy in the surgical treatment of humerus shaft fracture -anterolateral versus posterior approach: A systematic review and meta-analysis.
Although many studies have investigated iatrogenic radial nerve palsy (RNP) in humerus shaft fracture, there is inconsistent evidence on which approach leads to iatrogenic RNP. Moreover, no meta-analysis has directly compared the anterolateral and posterior approaches regarding iatrogenic RNP. In this systematic review and meta-analysis, the MEDLINE, Embase, and Cochrane Library databases were searched systematically for studies published before March 30, 2021. We included studies that (1) assessed the RNP in the surgical treatment of humerus shaft fracture and (2) directly compared the anterolateral and posterior approaches regarding the RNP. We performed synthetic analyses of the incidence of iatrogenic RNP and the recovery rate of iatrogenic RNP in humerus shaft fracture between the anterolateral and posterior approaches. Our study enrolled nine studies, representing 1303 patients who underwent surgery for humerus shaft fracture. After exclusion of traumatic RNP, iatrogenic RNP was reported in 35 out of 678 patients in the anterolateral approach and in 69 out of 497 patients in the posterior approach. Pooled analysis revealed that the incidence of iatrogenic RNP was significantly higher in the posterior approach than in the anterolateral approach (OR = 2.72; 95% confidence interval (CI), 1.70-4.35; P < 0.0001, I2 = 0%), but there was no significant difference in the recovery rates of iatrogenic RNP between the two approaches (OR = 1.55; 95% CI, 0.26-9.18; P = 0.63, I2 = 0%). In this meta-analysis, the posterior approach showed a higher incidence of iatrogenic RNP than the anterolateral approach in the surgical treatment of humerus shaft fracture. With limited studies, it is difficult to anticipate if any particular approach favors the recovery of iatrogenic RNP.


Young driver involvement in fatal motor vehicle crashes and trends in risk behaviors, United States, 1988-95.
To review trends and risk factors in fatal motor vehicle crashes (MVCs) for drivers aged 15-20 years. Fatality Analysis Reporting System data from 1988 to 1995 were used. Drivers were divided into three age strata: 15-17 years, 18-20 years, and > or = 21 years. Comparisons were made based on rates of driver involvement in fatal MVCs, the percentage of drivers involved in night time fatal MVCs, fatal MVCs without the use of restraints, and fatal MVCs with positive blood alcohol concentration. Over the eight years, the rate of driver involvement in fatal MVCs for those 15-17 dropped 15.5%; for those 18-20 years it dropped 22.0%, and for those > or = 21 years it declined 13.5%. When combining both age groups results were similar. In 1988, 60.4% of young drivers involved in fatal MVCs were not using restraints, but by 1995 the percentage dropped to 46.0%. Night time fatal crashes, the second most frequent risk behavior, declined from 41.7% in 1988 to 35.2% in 1995. Alcohol related traffic fatalities were responsible for 32.1% of fatal MVCs among young drivers in 1988 and for 20.3% in 1995. To accelerate these trends, implementation and evaluation of complete graduated driver licensing systems (GDLSs) is recommended. Under GDLSs, young drivers are subject to zero alcohol tolerance, curfews, and passenger restraint requirements.


Microarray analysis of thapsigargin-induced stress to the endoplasmic reticulum of mouse osteoblasts.
Activating transcription factor 4 (ATF4) protein has a dual role in osteoblasts. It functions as a responder to stress to the endoplasmic reticulum (ER) as well as a transcription factor for bone formation. Little is known about molecular pathways that can potentially lead to stress-induced apoptosis or homeostasis of extracellular matrix (ECM) molecules. Based on microarray-derived mRNA expression data for mouse osteoblasts (MC3T3 E1 cells, clone 4), we analyzed the ER-stress responses in the presence of 10 nM Thapsigargin using two computational approaches: "Gene Set Enrichment Analysis (GSEA)" and "Ingenuity Pathways Analysis (IPA)." GSEA presented a strong linkage to an expression pattern observed in the responses to hypoxia, and IPA identified two molecular pathways: ATF4-unlinked connective tissue development and ATF4-linked organ morphology. Real-time polymerase chain reaction (PCR) and Western blot analyses validated eIF2alpha-driven translational regulation as well as ATF4-linked transcriptional activation of transcription factors and growth factors including FOS, FGF-9, and BMP-2. Consistent with the role of p38 MAPK in hypoxia, phosphorylation of p38 MAPK was activated in nonapoptotic osteoblasts under surviving ER stress. Furthermore, the level of phosphorylated PERK was elevated. These results support cross-talk between p38 MAPK and ER kinase, presenting a similarity to the responses to hypoxia as well as a pathway toward connective tissue development and organ morphology.


RASopathy mutations open new insights into the mechanism of BRAF activation.
Spencer-Smith et al. (2022)1 investigate multiple functions of the BRAF cysteine-rich domain (CRD), finding distinct classes of RASopathy-associated BRAF mutations and unique features among RAF paralogs that may contribute to the spectrum of mutations observed in disease.


First case report of sepsis caused by Mycobacterium wolinskyi in chronic myelogenous leukemia.
Infections caused by Mycobacterium wolinskyi have rarely been reported, and essentially all were cellulitis and/or osteomyelitis related with traumatic event or surgical wound. Here, we present the 1st case of septic complication due to this organism in a patient with chronic myelogenous leukemia of the 1st but late chronic phase.


Refined study of the interaction between HIV-1 p6 late domain and ALIX.
The interaction between the HIV-1 p6 late budding domain and ALIX, a class E vacuolar protein sorting factor, was explored by using the yeast two-hybrid approach. We refined the ALIX binding site of p6 as being the leucine triplet repeat sequence (Lxx)4 (LYPLTSLRSLFG). Intriguingly, the deletion of the C-terminal proline-rich region of ALIX prevented detectable binding to p6. In contrast, a four-amino acid deletion in the central hinge region of p6 increased its association with ALIX as shown by its ability to bind to ALIX lacking the proline rich domain. Finally, by using a random screening approach, the minimal ALIX391-510 fragment was found to specifically interact with this p6 deletion mutant. A parallel analysis of ALIX binding to the late domain p9 from EIAV revealed that p6 and p9, which exhibit distinct ALIX binding motives, likely bind differently to ALIX. Altogether, our data support a model where the C-terminal proline-rich domain of ALIX allows the access of its binding site to p6 by alleviating a conformational constraint resulting from the presence of the central p6 hinge.


Maternal-biased H3K27me3 correlates with paternal-specific gene expression in the human morula.
Genomic imprinting is an epigenetic mechanism by which genes are expressed in a parental origin-dependent manner. We recently discovered that, like DNA methylation, oocyte-inherited H3K27me3 can also serve as an imprinting mark in mouse preimplantation embryos. In this study, we found H3K27me3 is strongly biased toward the maternal allele with some associated with DNA methylation-independent paternally expressed genes (PEGs) in human morulae. The H3K27me3 domains largely overlap with DNA partially methylated domains (PMDs) and occupy developmental gene promoters. Thus, our study not only reveals the H3K27me3 landscape but also establishes a correlation between maternal-biased H3K27me3 and PEGs in human morulae.


The role of radiocarpal injection arthrography and magnetic resonance imaging in the diagnosis of triangular fibrocartilage complex injuries.
To investigate the radiocarpal joint injection arthrography and magnetic resonance imaging for diagnosis of the triangular fibrocartilage complex (TFCC) injuries. Thirteen cases whose main complaints were ulnar wrist pain were given radiocarpal joint arthrography and eight of them were also given magnetic resonance imaging for evaluating the integrity of the triangular fibrocartilage complex. Ten of thirteen cases presented the leakage of contrast medium to distal radioulnar joint from the radiocarpal joint, in whom, 8 were demonstrated triangular fibrocartilage tear on magnetic resonance imaging, and 3 located at radial side, 2 at central, 3 at ulnar side. One of three cases which were demonstrated without the leakage of contrast medium in arthrography were displayed with marked TFCC tear on magnetic resonance imaging. The wrist arthrography can provide a definite diagnosis for triangular fibrocartilage disruption with higher sensitivity. magnetic resonance imaging not only demonstrates the site of triangular fibrocartilage disruption as the same value as wrist arthrography, but also displays the other related bony and soft tissues changes.


Demographic and Clinical Predictors of High Healthcare Use in Patients with Inflammatory Bowel Disease.
Inflammatory bowel disease (IBD) is a heterogeneous chronic inflammatory condition requiring significant healthcare expenditure. Subgroups of individuals contribute disproportionately to spending. We aimed to determine demographic and clinical factors predictive of high healthcare expenditures for IBD patients followed over a multiyear period. This was a registry analysis using a prospective observational, consented, natural history registry from a tertiary IBD center and associated medical charges, not including pharmacy expenses. The 100 patients with the highest medical charges (top 5%) were compared with the median 300 patients. Logistic regression determined demographic and clinical factors associated with high charge patients. IBD patients in the high charge group had significantly more unemployment (P < 0.0001), were of black race (P = 0.013), comorbid psychiatric illness (P = 0.002), hypertension (P = 0.01), diabetes (P = 0.004), opiate use (P < 0.0001), perianal involvement (P = 0.002), penetrating disease (P < 0.0001), and extensive colitis (P = 0.01). In multivariate analysis, unemployment (Crohn's disease [CD]: odds ratio [OR], 3.04; 95% confidence interval [CI], 1.32-7.02; ulcerative colitis [UC]: OR, 2.68; 95% CI, 1.20-5.99), psychiatric illness (UC: OR, 2.08; 95% CI, 1.03-4.19), opiates (CD: OR, 5.61; 95% CI, 2.67-11.82; UC: OR, 5.14; 95% CI, 2.52-10.48), prior surgery (CD: OR, 3.29; 95% CI, 1.59-6.82; UC: OR, 2.72; 95% CI, 1.39-5.32), penetrating CD (OR, 3.29; 95% CI, 1.02-10.62), and corticosteroid requirement (CD: OR, 3.78; 95% CI, 1.86-7.65; UC: OR, 2.98; 95% CI, 1.51-5.90) remained independently associated with high charges. High expenditure IBD patients were affected by more severe disease. The high prevalence of depression, anxiety, and chronic pain in these patients suggests the need for focused treatment of these comorbidities ultimately to reduce financial burden.


Development and nitrate reductase activity of sugarcane inoculated with five diazotrophic strains.
Diazotrophs are able to stimulate plant growth. This study aimed at evaluating the effect of inoculation of five diazotrophic strains on growth promotion and nitrate reductase (NR, EC 22.214.171.124) activity in sugarcane. An experiment was carried out from three stages of cultivation: sprouting, tubes, and in hydroponics. On the first two stages, seven treatments were adopted: uninoculated control; mixed inoculation with five strains; and individual inoculation with Gluconacetobacter diazotrophicus (Gd), Herbaspirillum rubrisubalbicans (Hr), Herbaspirillum seropedicae (Hs), Nitrospirillum amazonense (Na), and Paraburkholderia tropica (Pt). The four treatments showing the best performance were transferred to the hydroponic system for analysis of NR activity. Hs, Pt, and the mixture of all strains led to the highest seedling biomass in tubes, followed by Hr. In hydroponics, the mixture and the strain Hr had the highest growth-promoting effect. NR activity was influenced by inoculation only under low N supply conditions, with positive effect of Hr, Pt, and the mixture.


Confidentiality in crisis: Part I--The duty to inform.
To discuss the ethical and legal imperatives to protect third parties from harm in circumstances often believed to be protected by doctor-patient confidentiality. A review of recent legislative changes and legal decisions pertaining to a psychiatrist's duty to warn. The current legislative and legal climate presents many risks to the concept of doctor-patient confidentiality. Psychiatrists must carefully consider any guarantees of confidentiality made to patients and must discuss the limits of confidentiality when obtaining consent for treatment.


The selective NLRP3 inflammasome inhibitor MCC950 improves isoproterenol-induced cardiac dysfunction by inhibiting cardiomyocyte senescence.
Activation of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome contributes to heart failure (HF) pathogenesis. However, the effect of NLRP3 inhibition on β-adrenergic receptor agonist-induced HF remains unknown. Here, we evaluated the role of MCC950, a selective NLRP3 inhibitor, in isoproterenol (ISO)-induced cardiac dysfunction. Mice were administered ISO (30 mg/kg/day) for 14 days with or without MCC950 (10 mg/kg) injection every other day. Cardiac function and the extent of hypertrophy and fibrosis were measured by echocardiography, HE and Masson trichrome staining, respectively. Immunohistochemistry, quantitative real-time PCR and Western blotting were performed to investigate the impact of MCC950 on ISO-induced cardiac dysfunction. The levels of oxidative stress and cell senescence were detected in H9C2 cells to explore the mechanism of MCC950 on ISO-induced myocardial injury in vitro. We found that the NLRP3 inflammasome was significantly activated in response to ISO treatment in mice. Selective inhibition of the NLRP3 inflammasome by MCC950 ameliorated cardiac fibrosis, hypertrophy and inflammation in ISO-treated mice, ultimately improving heart function. Furthermore, MCC950 significantly inhibited ISO-induced oxidative stress in the myocardium, accompanied by increased superoxide dismutase 2 (SOD2) and nuclear factor erythroid 2-related factor 2 (Nrf2) protein. In addition, MCC950 attenuated cardiomyocyte death and senescence in ISO-treated H9C2 cells, which was attributed to the decreased oxidative stress. NLRP3 inhibition by MCC950 ameliorated ISO-induced cardiac dysfunction by inhibiting cardiomyocyte senescence and oxidative stress. Therefore, inhibition of the NLRP3 inflammasome may be a potential therapeutic strategy for preventing cardiac dysfunction, especially age-related HF.


Effects of composting on the fate of doxycycline, microbial community, and antibiotic resistance genes in swine manure and broiler manure.
Aerobic composting is an economical and effective technology that is widely used to treat animal manure. To study the fate of doxycycline (DOX), the microbial community, and antibiotic resistance genes (ARGs) during composting, aerobic composting of broiler manure and swine manure was carried out under natural environmental conditions. Aerobic composting effectively removed DOX (with a removal rate > 97%) and most ARGs from animal manure. The microbial diversity and the numbers of ARGs were higher in composted swine manure compared with composted broiler manure. The microbial community structure changed during composting, and the dominant phyla of broiler manure and swine manure changed from Firmicutes to Bacteroidetes and Proteobacteria, respectively. DOX changed the structure and relative abundance of the microbial community during composting, and the relative abundance of multidrug resistance genes and mobile genetic elements (MGEs) increased, which might lead to the risk of transmission of resistance in the environment. The C / N ratio, DOX concentration, Firmicutes, intl1, and intl2 were the key factors driving the change in ARGs during composting. These results help to reveal the effects of DOX on microbial communities, ARGs, and MGEs during composting and clarify the possible ways to reduce the risk of resistance gene transmission in the environment.


Specimen mammography for intraoperative margin assessment in breast conserving surgery: a meta-analysis.
In breast conserving surgery (BCS), specimen mammography is one of the most widely used intraoperative methods of assessing margin status. We performed a meta-analysis to evaluate the diagnostic accuracy of specimen mammography. Literature databases including PubMed, Cochrane Library, Web of Science, and EMBASE were searched prior to Jun 2022. A total of 1967 patients were included from 20 studies. A pooled analysis, heterogeneity testing, threshold effect testing, publication bias analysis, and subgroup analyses were performed from extracted data. The pooled weighted values were a sensitivity of 0.55 (95% confidence interval [CI], 0.47-0.63), a specificity of 0.85 (95% CI, 0.78-0.90), a diagnostic odds ratio of 7 (95% CI, 4-12), and a pooled positive likelihood ratio of 3.7 (95% CI 2.6-5.5). The area under the receiver operator characteristic curve was 0.75 (95% CI 0.71-0.78). In the subgroup analysis, the pooled specificity in the positive margin defined as tumor at margin subgroup was lower than the other positive margin definition subgroup (0.82 [95% CI: 0.71, 0.92] vs. 0.87 [95% CI: 0.80, 0.94], p = 0.01). Our findings indicated that specimen mammography was an accurate intraoperative imaging technique for margin assessment in BCS.


'Localism and intimacy, and… other rather imponderable reasons of that sort': A qualitative study of patient experience of community hospitals in England.
Debates over the value and contribution of community hospitals are hampered by a lack of empirical assessment of the experience of patients using these services. This paper presents findings from a study which included a focus on patient and family-carer experiences of community hospitals in England. We adopted a qualitative design involving nine case study hospitals. Data collection included interviews with patients (n = 60), carers (n = 28) and staff (n = 89). Through patients and carers highlighting the value of community hospitals feeling 'close to home', providing holistic and personalised care and supporting them through difficult transitions, the study confirms the importance of functional and interpersonal aspects of care, while also highlighting the importance of social and psychological aspects. These included having family, friends and the community close, maintaining social connections during periods of hospital treatment, and feeling less anonymous and anxious when attending the hospital due to the high levels of familiarity and connectedness. Although the experiences uncovered in this study were not uniformly positive, patients and carers placed a high overall value on the care provided by community hospitals, often arguing that these were distinctive when compared to their experiences of using other health and care services. The study suggests the need to weigh the full range of these dimensions of patient experience-functional, interpersonal, social and psychological-when assessing the role and contribution of community hospitals.


Effects of galanin-like peptide (GALP) on locomotion, reproduction, and body weight in female and male mice.
Galanin-like peptide (GALP) has been implicated in the neuroendocrine regulation of both feeding and reproduction. In male rodents and primates, intracerebroventricular (icv) infusions of GALP stimulate luteinizing hormone (LH) release, induce Fos expression in brain areas implicated in feeding and reproduction, and affect food intake and body weight in rodents. In gonad-intact and castrated male rats, icv administration of GALP also stimulates male sexual behavior. While the effects of GALP on male physiology and behavior are well documented, no studies have addressed such a role of GALP in females. We tested the effects of icv GALP infusions on LH release, locomotor activity, motor control, and body weight regulation in adult ovariectomized female mice hormonally primed with estradiol benzoate and progesterone. In addition, sexually-experienced male and female mice were treated with GALP and tested for sexual behavior. In females, GALP reduced open-field locomotor activity, the ability to maintain grip on an accelerating rotarod, and 24-h body weight in a dose-dependent manner. GALP also increased LH secretion in female mice, an effect that was blocked by pre-treatment with Antide, a gonadotropin-releasing hormone (GnRH) type-1 receptor antagonist. GALP infusions slightly decreased the occurrence of lordosis behavior in female mice and significantly increased the latencies with which females displayed receptivity. Unlike previous reports in male rats, GALP inhibited male sexual behavior in mice. Our data indicate that in female mice, GALP stimulates LH release via GnRH, and decreases body weight, motor control, and locomotor activity via GnRH-independent pathways. Furthermore, our sexual behavior and locomotor findings suggest species-specific differences in the mechanism and/or location of GALP action in the brains of rats and mice.


Singlet oxygen induced mutagenesis of benzo[a]pyrene derivatives.
Singlet oxygen activates the mutagenicity of several benzo[a]pyrene (BP) derivatives in the absence of mammalian metabolic action. This has been demonstrated using a separated-surface-sensitizer system for generating chemically pure singlet oxygen, eliminating most of the complications that arise with singlet oxygen generation by conventional photosensitization. Salmonella typhimurium bacteria were exposed to singlet oxygen in the presence of certain BP derivatives and the mutation frequency determined with an azaguanine forward mutation assay. The mutation frequency was increased by exposure to singlet oxygen compared to light-only controls for those BP derivatives that were saturated at either the 7,8 or 9,10 positions but not both. The increase in mutation frequency depends on both the concentration of BP derivative and on the dose of singlet oxygen. Mutation frequency was also significantly increased when bacteria were treated with a solution of trans-7,8-dihydrodiol-BP that had been separately exposed to singlet oxygen, unequivocally demonstrating that the mutagenicity is due to the formation of a product of BP derivative oxidation by singlet oxygen and that this product has a lifetime at least on the order of minutes in acetonitrile. The requirement for singlet oxygen rather than some other form of reactive oxygen was confirmed by determination of the gas phase lifetime of the intermediate responsible for activating mutagenicity. This was performed by measuring the dependence of the mutation frequency on the distance separating the sensitizer from the target. This gives a value of 88 +/- 35 ms, which is in excellent agreement with the mean value of 89 ms calculated from previous independent determinations of the gas phase lifetime of singlet oxygen reported in the literature.


Slow progress in diarrhea case management in low and middle income countries: evidence from cross-sectional national surveys, 1985-2012.
Diarrhea remains to be a main cause of childhood mortality. Diarrhea case management indicators reflect the effectiveness of child survival interventions. We aimed to assess time trends and country-wise changes in diarrhea case management indicators among under-5 children in low-and-middle-income countries. We analyzed aggregate data from Demographic and Health Surveys and Multiple Indicator Cluster Surveys done from 1986 to 2012 in low-and-middle-income countries. Two-week prevalence rates of diarrhea, caregiver's care seeking behavior and three case management indicators were analyzed. We assessed overall time trends across the countries using panel data analyses and country-level changes between two sequential surveys. Overall, yearly increase in case management indicators ranged from 1 · 3 to 2 · 5%. In the year 2012, <50% of the children were given correct treatment (received oral rehydration and increased fluids) for diarrhea. Annually, an estimated 300 to 350 million children were not given oral rehydration solutions, or recommended home fluids or 'increased fluids' and 304 million children not taken to a healthcare provider during an episode of diarrhea. Overall, care seeking for diarrhea, increased from pre-2000 to post-2000, i.e. from 35 to 45%; oral rehydration rates increased by about 7% but the rate of 'increased fluids' decreased by 14%. Country-level trends showed that care seeking had decreased in 15 countries but increased in 33 countries. Care seeking from a healthcare provider increased by ≥10% in about 23 countries. Oral rehydration rates had increased by ≥10% in 15 countries and in 30 countries oral rehydration rates increased by <10%. Very limited progress has been made in the case management of childhood diarrhea. A better understanding of caregiver's care seeking behavior and health care provider's case management practices is needed to improve diarrhea case management in low- and-middle-income countries.


The pulmonary vasculature in haematite lung.
A histological study was made of the pulmonary vasculature in two cases of haematite lung. Between fibrotic nodules in the lung the muscular pulmonary arteries showed the development of longitudinal muscle in the intima, a change thought to be associated with stretch and distortion of these vessels. In some arteries this muscular layer in the intima showed secondary fibrosis. No muscularized pulmonary arterioles were seen, indicating an absence of constriction of the terminal portions of the pulmonary arterial tree. Pulmonary arteries in fibrotic areas had become progressively engulfed by the fibrous tissue. The occlusive and obliterative vascular changes in 'haematite lung' are in reality those of silicosis which are brought about by the inhalation of silica particles with the iron sesquioxide. The only feature peculiar to haematite lung is the intense accumulation of iron-containing dust in and around the pulmonary blood vessels.


Presentation, Morbidity and Treatment Outcome of Acromegaly Patients at a Single Centre.
The management of acromegaly, a rare and potentially curable disease, has undergone a paradigm shift in the past few decades. Many of the treatment modalities recommended for acromegaly are either too expensive or not available in many parts of India. There is a dearth of treatment and outcome data in Indian patients. Our aim was to study the clinical presentation, hormonal profile, radiology, management, and outcome of the disease at our center. Fifty one patients with acromegaly who attended the Department of Endocrinology, SKIMS, Srinagar, between October 2015 and April 2017, were included in the study. Clinical and hormonal profiles, comorbidities, treatment modalities, and outcome were evaluated. The gender distribution was equal with the mean age of 42.3 ± 10.9 years at diagnosis. The majority (41) of the patients had macroadenoma. The most common presenting manifestations were acral enlargement and headache. Hypertension was present in 23, musculoskeletal manifestations in 19, and diabetes mellitus in 11 patients. Surgery was the most common method of treatment. Preoperatively only one patient with micro-adenoma had hypocortisolism, which was persistent in postoperative period, while no patient had preoperative or postoperative hypothyroidism or hypogonadism. As per the present consensus criteria, 23.7% patients achieved disease control (40% with microadenoma and only 19.5% with macroadenoma). The surgical complications occurred in 5 patients-CSF leak in 3 meningitis in 2 patients all except one having macroadenoma. The presentation of disease was generally comparable to that reported in literature. Cure rates were significantly lower than those reported from many large centers.


Toxic epidermal necrolysis in a 6-week-old infant.
Toxic epidermal necrolysis was documented in a 6-week-old infant with Klebsiella pneumoniae sepsis who received many medications. We inoculated infant mice with the K. pneumoniae isolate but were unable to produce histologic changes resembling those seen in our patient. This condition should be included in the differential diagnosis of severe drug reactions in very young infants with clinical scalded-skin syndromes.


Cumulative Disadvantage and Youth Well-Being: A Multi-Domain Examination with Life Course Implications.
The accumulation of disadvantage has been shown to increase psychosocial stressors that impact life course well-being. This study tests for significant differences, based on disadvantage exposure, on youths' emotional and physical health, as well as family supports, peer assets, and academic success, which hold potential for resilience and amelioration of negative health outcomes. A 12 item cumulative disadvantage summed index derived from surveys of a racially and socioeconomically diverse sample of urban high school seniors (n=9,658) was used to distinguish youth at low, moderate, and high levels. Findings supported hypothesized stepped patterns such that as multiple disadvantages accumulate, a concomitant decline is evident across the assessed outcome variables (except positive academic identity). Post-hoc tests indicated a pattern of groups being significantly different from one another. Overall, results lend support for an additive stress load associated with stacked disadvantage, with implications for continuing trends into adulthood as well as preventive interventions.


Retention of hemopoiesis in tail vertebrae of newborn rats.
In newborn rats, the marrow cavity of tail vertebrae is hemopoietic and contains no adipose tissue. The latter develops soon after birth to replace the hemopoietic tissue within the nonexpansile volume of the marrow cavity. By transposing the tail into the warmer environment of the abdomen, hemopoiesis was retained, and the development of adipose tissue was prevented in the transposed segment, when the operation was done in preweanling but not in adult animals. Systemic stimuli of erythropoiesis (phlebotomy, induced hemolysis) acted synergistically with the temperature increment to retain hemopoiesis. The findings support the concept that adipose cells in the yellow marrow are relatively stable and once developed, they are not readily mobilized. The findings may also explain the discrepancies in the results obtained by rat tail transposition.


Constitutive expression and inducibility of CYP1A1 in the H9c2 rat cardiomyoblast cells.
Cardiomyocytes are a valuable tool for studying the drug metabolizing enzymes in the heart. However, isolated cardiomyocytes are rather fragile and difficult to isolate. Therefore, there is an urgent need for an in vitro cell line model. The H9c2 cells are commonly used as an in vitro model for studying the cellular mechanisms and signaling pathways involved in drug-induced cardiotoxicity. These cells maintain many molecular markers of cardiomyocytes and show morphological characteristics of immature embryonic cardiomyocytes. Therefore, in the present study we examined the expression and inducibility of CYP1A1 in the H9c2 rat cardiomyoblast cells. Our results showed that treatment of H9c2 cells with the CYP1A1 inducer, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) significantly induced CYP1A1 at mRNA, protein, and activity levels in a concentration-dependent manner. The RNA synthesis inhibitor, actinomycin D, completely blocked the CYP1A1 mRNA induction by TCDD, indicating the requirement of de novo RNA synthesis through transcriptional activation. In conclusion, we demonstrated for the first time the constitutive expression and inducibility of CYP1A1 in H9c2 cells. Therefore, this cell line offers a unique in vitro model to study the role of CYP1A1 in the pathogenesis of various cardiovascular diseases.


Analysis of the (H-2b X H-2k)F1-restricted response to insulin. Ab alpha Ak beta hybrid Ia molecules restrict the response towards the glutamic acid A4 epitope.
The aim of these studies was to characterize the (H-2b X H-2k)F1-unique restriction element(s) responsible for presentation of bovine insulin (BI) to a long-term cultured T-cell line (BK-BI-1.2). (B10.BR X bm12)F1 spleen cells, which express a normal Ab alpha Ak beta molecule but a mutated Ak alpha Abm12 beta product on their cell surface, were perfectly able to act as BI-presenting cells. Antibody inhibition experiments with antibodies directed at I-Ak products revealed that monoclonal antibody 10-2.16, which reacts with the Ak beta polypeptide chain, abrogated BI-directed T-cell proliferation, whereas antibody H116-32.R5 with specificity for the Ak alpha chain was not inhibitory. These results identified the Ab alpha Ak beta complex as restriction structure. Recognition of BI in the context of the Ab alpha Ak beta molecule depended on the glutamic acid residue in position 4 of the A chain of bovine insulin. Twenty to twenty-five percent of the secondary proliferative response of (B10 X B10.BR)F1 lymph node T cells primed with BI in vivo was directed at the A4 determinant, suggesting that BK-BI-1.2 T blasts are representative of T-cell clones with measurable frequency. In (B10.BR X bm12)F1 mice, which lack a functional Ab alpha Ab beta restriction element, up to 80% of the proliferative response was dependent on the A4 epitope.


Contribution to the ethnobotanical, phytochemical and pharmacological studies of traditionally used medicinal plants in the treatment of dysentery and diarrhoea in Lomela area, Democratic Republic of Congo (DRC).
In order to collect ethnobotanical information about antidiarrhoeal plants, we performed inquiries among traditional healers, community leaders, and native people of Lomela villages in Congo. Six medicinal plants widely used in this region were designated as having antidysenteric and antidiarrhoeal properties. These six medicinal plants were screened for groups of phytochemical compounds with antibacterial and antiamoebic activities. They were found to contain tannins, alkaloids, saponins, flavonoids, sterols and/or triterpenes and reducing sugars. Of the six tested plants, three showed prominent antibacterial activity whereas two acted against Entamoeba histolytica. The usefulness of the phytochemical bases and biological activities of these plants as potential source of antidiarrhoeal remedies is discussed.


Metal(oid)s in plastic debris, with distinct features, from Spanish Mediterranean beaches with different anthropogenic pressure: Are these particles potential monitors for metal pollution?
Metal(oid)s concentrations have been quantified in plastic pieces collected from four beaches located in the Mediterranean coast of Spain with different characteristics (i.e. anthropogenic pressure, zone). Metal(oid)s content was also related to selected plastic criteria (i.e. color, degradation status, polymer). The selected elements were quantified with mean concentrations in the sampled plastics with the following order: Fe > Mg > Zn > Mn > Pb > Sr > As > Cu > Cr > Ni > Cd > Co. Moreover, black, brown, PUR, PS, and coastal line plastics concentrated the higher metal(oid)s levels. Local of sampling (influence of mining exploitation) and severe degradation were key factors for uptake of metal(oid)s from water by plastics as modification of surfaces strengths their adsorption capacity. Determined high levels of Fe, Pb and Zn in plastics reflected the pollution degree of the marine areas. Therefore, this study is a contribution for the potential use of plastics as pollution monitors.


Embracing Technology for Capacity Building in Mental Health: New Path, Newer Challenges.
Technology driven capacity building initiatives are the way to break the barrier of shortage of mental health human resources in India. This new path, while is a welcome step, comes with its own set of challenges. In one prototypic project that is being implemented in Ramanagara District of Karnataka, a south Indian state, we encountered many such issues. They ranged from issues related to availability of dedicated space to set up the hub-studio, inconsistent internet connectivity (particularly in remote areas) and inadequate digital literacy among the grassroot community health workers who hail from villages. This article summarises these challenges and ends by looking into ways and means of overcoming them.


Percutaneous absorption of nicardipine and ketorolac in rhesus monkeys.
Vehicle effects on the percutaneous absorption of nicardipine base, nicardipine hydrochloride, ketorolac acid, and ketorolac tromethamine were determined using the rhesus monkey as an in vivo model for human skin penetration. Vehicles investigated included blends of propylene glycol, trimethylene glycol, ethanol, Azone, Tween 20, water, and long-chain fatty acids. Formulations were prepared such that the compound dose, application area, and percentage saturation of the compound in the vehicle were held constant. Variations in absorption of the compounds were therefore attributable to vehicle effects. Each formulation was applied to three monkeys for a period of 24 hr using 10 Hill Top Chambers. Plasma samples were taken at appropriate intervals for 36 to 48 hr. The results indicated that trimethylene glycol and Tween 20 did not enhance absorption of the test compounds despite claims by other investigators. Azone and ethanol provided moderate enhancement of both the rate and the extent of absorption, while long-chain fatty acids in combination with propylene glycol significantly enhanced penetration. In general, higher fluxes were observed with the more lipophilic compounds nicardipine base and ketorolac acid as compared to the hydrochloride and tromethamine salts.


Medical and nonmedical use of prescription pain medication by youth in a Detroit-area public school district.
The purpose of this descriptive study was to examine the nonmedical use of prescription pain medications in a sample of public school students in the Detroit metropolitan area. The Web-based survey occurred during a two-week period in May 2003 and drew on a diverse population between the ages of 10 and 18 years. An 87% response rate was achieved, providing a final sample of 1017 students. Twenty-two percent of girls and 10% of boys reported lifetime nonmedical use of a pain medication (chi2 = 25.2, d.f. = 1, p < 0.001). Fifteen percent of girls and 7% of boys reported past year nonmedical use (chi2 = 12.7, d.f. = 1, p < 0.01). Compared to nonusers, nonmedical users of prescription pain medication were seven times more likely to smoke cigarettes, five times more likely to drink alcohol and smoke marijuana, almost four times more likely to binge drink, and eight times more likely to have used other illicit drugs. Of those reporting lifetime nonmedical use of prescription pain medication, 70% noted how they obtained the drugs; 34% reported getting the drugs from a family member, 17% from a friend and 14% from a dealer or theft.


Simulation of crack propagation in alumina with ab initio based polarizable force field.
We present an effective atomic interaction potential for crystalline α-Al(2)O(3) generated by the program potfit. The Wolf direct, pairwise summation method with spherical truncation is used for electrostatic interactions. The polarizability of oxygen atoms is included by use of the Tangney-Scandolo interatomic force field approach. The potential is optimized to reproduce the forces, energies, and stresses in relaxed and strained configurations as well as {0001}, {1010}, and {1120} surfaces of Al(2)O(3). Details of the force field generation are given, and its validation is demonstrated. We apply the developed potential to investigate crack propagation in α-Al(2)O(3) single crystals.


Insights into the inhibitory activities of neolignans and diarylnonanoid derivatives from nutmeg (Myristica fragrans Houtt.) seeds on soluble epoxide hydrolase using in vitro and in silico approaches.
Two new neolignans, myrifralignans F-G (14 and 18), four new diarylnonanoid derivatives, myrifragranones A-D (21-24), and 18 known compounds were isolated and structurally elucidated from nutmeg (Myristica fragrans Houtt.) seeds. The absolute configurations of these secondary metabolites were determined using the electronic circular dichroism technique. The inhibitory potential of these isolated compounds on soluble epoxide hydrolase (sEH) was investigated for the first time. Among them, malabaricones B and C (19 and 20) and four new compounds 21-24 displayed inhibitory activities against sEH, with IC50 values ranging from 14.24 to 46.35 µM. Additionally, the binding mechanism, key binding interactions, stability, and dynamic behaviour of the active compounds with the sEH enzyme were analysed using in silico molecular docking and dynamics simulations. Our findings suggest that nutmeg could become a promising natural source for discovering and developing new sEH inhibitors.


Smad2 and Smad3 expressed in skeletal muscle promote immobilization-induced bone atrophy in mice.
Skeletal muscle is known to regulate bone homeostasis through muscle-bone interaction, although factors that control this activity remain unclear. Here, we newly established Smad3-flox mice, and then generated skeletal muscle-specific Smad2/Smad3 double conditional knockout mice (DcKO) by crossing Smad3-flox with skeletal muscle-specific Ckmm Cre and Smad2-flox mice. We show that immobilization-induced gastrocnemius muscle atrophy occurring due to sciatic nerve denervation was partially but significantly inhibited in DcKO mice, suggesting that skeletal muscle cell-intrinsic Smad2/3 is required for immobilization-induced muscle atrophy. Also, tibial bone atrophy seen after sciatic nerve denervation was partially but significantly inhibited in DcKO mice. Bone formation rate in wild-type mouse tibia was significantly inhibited by immobilization, but inhibition was abrogated in DcKO mice. We propose that skeletal muscle regulates immobilization-induced bone atrophy via Smad2/3, and Smad2/3 represent potential therapeutic targets to prevent both immobilization-induced bone and muscle atrophy.


A nationwide survey of the use of the laparoscopic power morcellator.
Laparoscopic power morcellator (LPM) can be used for tissue retrieval through laparoscopic port site, but the dissemination of uterine and/or myoma tissues is a serious complication. To study the use of LPM for uterine fibroid treatment in Japan, we aimed to perform two national cross-sectional surveys comprising multiple questionnaires. The first survey (2011-2013) was conducted in November 2014, and 203 medical institutions responded. The second survey (2017-2019) was conducted in December 2020, and 302 medical institutions were investigated. Overall, 72 104 and 120 425 surgeries and 0.04% and 0.05% cases of postoperative malignancy diagnosis were reported in the first and second surveys, respectively. Magnetic resonance imaging was performed in >90% of the cases in the first and second surveys as preoperative examinations. The frequency of LPM at hysterectomy was 8.9% and 4.6% and the frequency of LPM at laparoscopic myomectomy was 80.4% and 54.8% in the first and second surveys, respectively; both the parameters decreased in the second survey. It is impossible to completely exclude malignant diseases even if extensive preoperative diagnosis has been done before surgery. Therefore, the use of LPM in patients requires careful attention and informed consent in Japan.


[Imaging of locally advanced prostate cancer : Importance of ultrasound and especially MRI].
Prostate cancer is the most common male malignant tumor in Germany, which thus places growing demands on differentiated imaging and risk-adapted therapeutic approaches. Multiparametric MRI (mpMRI) of the prostate enables reliable detection of clinically significant cancers and is currently the leading imaging modality for the detection, characterization, and local staging of prostate cancer. According to the German S3 guideline, mpMRI of the prostate is currently primarily recommended in patients with previous negative TRUS biopsies and persisting tumor suspicion. The serial use of mpMRI in the pretherapeutic setting can support individual therapy planning of patients with locally advanced prostate cancer in the near future.


Gm allotypes in IgA deficiency.
Gm phenotypes were examined in 90 Swedish IgA-deficient (less than 0.05 g/litre of serum IgA) donors and 40 normal first and second degree relatives of six of these donors. The G1m1,2, G3m5 and Km1 frequency in the group of IgA-deficient donors did not differ from that found in the normal population. Among the relatives, HLA and/or Gm identical normal sibs were observed. Anti-IgA antibodies were present in 29 of the IgA-deficient donors and anti-IgG in seven. No association between the two was found. A statistically significant association between the G1m-2 phenotype and the presence of anti-IgA antibodies was observed. When subdivided according to HLA type, a non-random distribution of Gm phenotypes was seen in HLA-B8/DR3 positive individuals with anti-IgA antibodies (HLA-B8/DR3 being the haplotype associated with IgA deficiency). These data suggest an association between IgA deficiency, anti-IgA and the studied Gm allotypes.


Effects of cyclosporin A on humoral immunity to ticks and on cutaneous immediate and delayed hypersensitivity reactions to Ixodes ricinus L. salivary-gland antigens in re-infested rabbits.
When rabbits are repeatedly infested with Ixodes ricinus L. adults, they acquire resistance to these ticks. A humoral response occurs and the skin of the host becomes progressively sensitized to the saliva of the ectoparasites. The present study examined the effects of cyclosporin A on these two aspects of immunity in re-infested rabbits. Using the enzyme-linked immunosorbent assay (ELISA), moderate suppression of the secondary IgG response to bites of these ticks was observed in animals given this immunosuppressive drug. The agent blocked the immediate cutaneous (type I) reaction normally developed in response to the intradermal injection of I. ricinus salivary gland antigens, as detected by measuring the skinfold thickness. The same method revealed a decreased delayed (type IV) hypersensitivity to these antigens. The present experiments demonstrate the major role of cyclosporin A-sensitive cells (mostly T-lymphocytes, mast cells and basophils) involved in the complex phenomenon of resistance to ticks.


The bacterial flagellar switch complex is getting more complex.
The mechanism of function of the bacterial flagellar switch, which determines the direction of flagellar rotation and is essential for chemotaxis, has remained an enigma for many years. Here we show that the switch complex associates with the membrane-bound respiratory protein fumarate reductase (FRD). We provide evidence that FRD binds to preparations of isolated switch complexes, forms a 1:1 complex with the switch protein FliG, and that this interaction is required for both flagellar assembly and switching the direction of flagellar rotation. We further show that fumarate, known to be a clockwise/switch factor, affects the direction of flagellar rotation through FRD. These results not only uncover a new component important for switching and flagellar assembly, but they also reveal that FRD, an enzyme known to be primarily expressed and functional under anaerobic conditions in Escherichia coli, nonetheless, has important, unexpected functions under aerobic conditions.


High-performance subambient radiative cooling enabled by optically selective and thermally insulating polyethylene aerogel.
Recent progress in passive radiative cooling technologies has substantially improved cooling performance under direct sunlight. Yet, experimental demonstrations of daytime radiative cooling still severely underperform in comparison with the theoretical potential due to considerable solar absorption and poor thermal insulation at the emitter. In this work, we developed polyethylene aerogel (PEA)-a solar-reflecting (92.2% solar weighted reflectance at 6 mm thick), infrared-transparent (79.9% transmittance between 8 and 13 μm at 6 mm thick), and low-thermal-conductivity (k PEA = 28 mW/mK) material that can be integrated with existing emitters to address these challenges. Using an experimental setup that includes the custom-fabricated PEA, we demonstrate a daytime ambient temperature cooling power of 96 W/m2 and passive cooling up to 13°C below ambient temperature around solar noon. This work could greatly improve the performance of existing passive radiative coolers for air conditioning and portable refrigeration applications.


Studies on bursting pacemaker potential activity in molluscan neurons. II. Regulations by divalanet cations.
Identified cells in Aplysia (R15, R2, LPG) and cell 11 in Otala have been used to investigate the effects of divalent cations, temperature, pH and ouabain on neuronal activity. Divalent cations act primarily to regulate the appearance of bursting pacemaker potential (BPP) activity in these cells. These ions are necessary for B generation and will inhibit its appearance at high concentrations (Ca greater than Mg greater that greater than Sr). In addition, Ca is involved in the seasonal modulation of BPP activity in a neurosecretory cell in Otala. Monovalent cations play secondary roles as regulators of BPP activity by competing with divalent cations for the sites involved in the regulation of the (probable) monovalent conductances underlying BPPs. The effects of pH, temperature and ouabain on membrane properties and BPP activity are partly related to their interaction with divalent cations. The results described indicate important roles for divalent cations in the regulation of the expression of BPP activity and its underlying membrane properties both in different nerve cells and in the same cell during dormancy and activity of the snails.


On the iteration of coincidence summing correction for determination of gamma-ray intensities.
In order to determine the γ-ray emission intensities of nuclei far from the β-stability line with HPGe detectors under large solid-angle geometry, coincidence summing corrections should be performed, even if full energy peak efficiencies of detectors are accurately measured with standard sources. Because the summing effects depend on decay schemes and emission intensities, the correction needs to be iterated several times starting from the initial values of intensities obtained directly from the measured peak counts of γ-rays. Considering (134)Cs, (154)Eu and (56)Co as typical examples, we discuss the number of iterations of summing correction required for self-consistency with respect to the total efficiencies of the detectors.