Fine structure of translocation breakpoints in leukemic blasts with chromosomal translocation t(4;11): the DNA damage-repair model of translocation.
Chromosomal translocations t(4;11) are regularly associated with a specific type of acute leukemias and probably initiate the development of this disease. It has been proposed by others, that these translocations are mediated by recombinases of the immune system. The breakpoints on both derivative chromosomes for three t(4;11) leukemia-derived cell lines and primary blasts from two patients have been analysed here in detail. The results revealed that: (a) multiple double- or single-stranded DNA breaks must have occured near the translocation breakpoints on both participating chromosomes; and (b) DNA fragments flanked by these breaks must have either been deleted, inverted or duplicated during the translocation process. We found no evidence for the involvement of specific target sequences and recombinases of the immune system. Similar characteristic features were observed by re-interpretation of published t(6;11) and t(9;22) translocation data. Therefore we present a new model for the generation of these translocations which poses, that these translocations are reciprocal but not balanced at the fine structure level and that the DNA damage-repair machinery is likely involved in producing the final structure of the translocation breakpoint.


Management of Mastalgia.
Breast pain is a common symptom in most women during their lifetime, and many times is self-limited. Mastalgia is categorized into 3 main groups: cyclic, noncyclic and extramammary. A good history, examination and targeted imaging can help to delineate the underlying cause of mastalgia and therefore guide treatment options. Diet, medications, stress, hormonal fluctuations, and an ill-fitting bra can be contributing factors for physiologic causes of mastalgia. Breast cancer is rarely a cause but should be excluded. Reassurance, support, dietary changes, nonsteroidal anti-inflammatory drugs and occasionally hormonal medications are options to help with improving breast pain.


ASSOCIATION OF FLOW SIGNALS WITHIN POLYPS ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY WITH TREATMENT RESPONSES AFTER COMBINATION THERAPY FOR POLYPOIDAL CHOROIDAL VASCULOPATHY.
To evaluate the changes of blood circulation within the polypoidal lesions by OCT angiography in eyes with polypoidal choroidal vasculopathy after combination therapy with aflibercept and photodynamic therapy. A total of 46 eyes from 46 patients who underwent the combination therapy for polypoidal choroidal vasculopathy were followed for more than 6 months. OCT angiography, covering an area 6 mm2 × 6 mm2 including the macula, were performed at baseline, 2 weeks, and 3 months and 6 months post-treatment. The subretinal fluid resolved within 3 months after treatment in 44 eyes (95.7%), and 27 eyes (58.7%) showed no recurrence, with no additional treatment. Seventeen eyes (37.0%) showed recurrence, and two eyes (4.3%) showed poor response. On OCT angiography at 2 weeks after treatment, flow signals were detected in 3 of 27 eyes (11.1%) without recurrence and in 8 of 19 eyes (42.1%) with recurrence or poor responses. A detectable flow signal at 2 weeks was significantly associated with recurrence or poor response (P = 0.032). Persistent flow signals within polyps on OCT angiography at 2 weeks after combination therapy suggest less effectiveness of the initial treatment.


A consensus method for updating psychosocial measures used in NIOSH health hazard evaluations.
An expert panel was convened to select practical, valid psychosocial measures for use during National Institute for Occupational Safety and Health field investigations. A taxonomy of psychosocial constructs was developed using existing taxonomies and criteria regarding the malleability, actionability, and validity of constructs. Panel members identified measures for each construct based on their expertise and experience. Measures were selected on the basis of the following criteria: practicality, brevity, validity, availability of existing data, and lack of confounds between psychosocial constructs and outcomes. The panel came to a consensus in recommending 24 measures representing 22 constructs. It is important that the National Institute for Occupational Safety and Health regularly evaluates its methodologies to ensure it is in line with current best practices. The measures identified will be used modularly in the National Institute for Occupational Safety and Health fieldwork depending on the nature of the evaluation request, industry type, and worker population.


Phenotypic and genotypic characterization of Hodgkin's disease.
Although a few studies have reported clonal cytogenetic changes in Hodgkin's disease (HD), their correlation with histologic groups is poorly defined. This is because of insufficient numbers of clonally abnormal cases ascertained in each of these studies, an inherent problem associated with the cytogenetic studies of HD. In this report we present results of pathologic, phenotypic, and genetic studies on 29 HD tumors consecutively ascertained by us and the results of a comprehensive analysis of the cytogenetic data available in the literature. In our series 75% of the tumors were positive for Epstein-Barr virus (EBV) by polymerase chain reaction (PCR) assay. A higher frequency of EBV-positive tumors showed clonal karyotypic abnormalities than the EBV-negative tumors. Unlike the case in the previous reports, none of the 24 tumors studied by PCR showed the presence of t(14;18) (q32;q21)-carrying cells. From the comprehensive analysis of the literature, we identified recurring nonrandom numerical changes, deletions, and chromosome breaks in HD. Some of these are associated either with nodular sclerosis or with mixed cellular histologies. A comparison of the pattern of these nonrandom cytogenetic changes in HD and those reported for non-Hodgkin's lymphomas (NHL) identified common deletions and breaks between them. These common genetic lesions probably play a role in disease evolution.


Combinatorial prophylactic effect of phlorotannins with photobiomodulation against tracheal stenosis.
Several conventional treatments are used to manage tracheal stenosis after intubation and surgical procedures; however, patients are at risk of restenosis because of the absence of effective preventative therapy. In this study, we evaluate the biomodulatory effect of PT-combined blue light (BL) PBM in tracheostomal stenosis-induced animal models. The PT-combined BL group showed a significant decrease in the fibrotic protein synthesis by downregulating the release of stenosis-triggering fibrotic signals, without cytotoxicity or thermal damage. Moreover, the combined treatment ameliorated excessive granulation and collagen formation, and consequently preserved the opening of the tracheostoma ten days after fenestration. The current study demonstrated the biomodulatory effect of PT-combined BL on human tracheal fibroblasts and tracheal fenestration rodent models. Hence, PT-combined BL has the potential to be an effective preventative treatment for tracheal stenosis but also as an alternative option for fibrotic disorders.


[Effect of Basil Polysaccharide on Histone H3K9me2 Methylation and Expression of G9a and JMJD1A in Hepatoma Cells Under Hypoxic Conditions].
To study the effect of basil polysaccharide on the expression of histone methyltransferase G9a, demethylase JMJD1A and histone H3K9me2 methylation level in hepatoma cells MHCC97H and MHCC97L under hypoxic conditions, in order to explore the regulatory effect of basil polysaccharide on the epigenetics of hepatoma cells. Cobalt chloride(CoCl2) was used to simulate hypoxic, MHCC97H and MHCC97L hepatoma cells hypoxia model was established in vitro,and then intervened with different concantration of basil polysaccharide intervened 24 h. The expression of HIF-1α, G9a and JMJD1A mRNA in hepatoma cells were detected by real time fluorescent quantitative PCR. The expression of HIF-lα, G9a, JMJD1A protein and histone H3K9me2 methylation level was detected by Western-blot method. Basil polysaccharide down-regulated the expression of HIF-lα, G9a, JMJD1A mRNA and protein and histone H3K9me2 methylation level in MHCC97H cells under hypoxic condition,and down-regulated the expression of HIF-lα mRNA and protein and histone H3K9me2 methylation level in MHCC97L cells under hypoxic condition(P <0. 05). Basil polysaccharide can regulate histone H3K9me2 methylation levels in hepatoma cells MHCC97H and MHCC97L which have different metastatic potential under hypoxic conditions. On hepatoma cell MHCC97H, the regulation of histone H3K9me2 methylation is associated with histone methyltransferase G9a and demethylase JMJDlA. In hepatoma cell MHCC97L, the regulation of histone H3K9me2 methylation was probably through other pathways.


Nicotine serves as an effective reinforcer of intravenous drug-taking behavior in human cigarette smokers.
Although numerous studies have documented that nicotine can function as an effective reinforcer of intravenous self-administration behavior in animals, it has not been clearly shown to maintain intravenous self-administration behavior above vehicle placebo levels in humans. To compare the reinforcing effectiveness of nicotine versus saline placebo in human research volunteers responding under fixed-ratio (FR) schedules of intravenous drug self-administration while systematically increasing response requirements. Eight male cigarette smokers resided in an inpatient research unit. During 3-h sessions, intravenous injections of nicotine and saline were available concurrently and were contingent on responding (pulling a lever). Nicotine dose (0.75, 1.5, 3.0 mg/injection), time out (TO) value after each injection (1-20 min) and FR response requirement (10-1600) were varied in different subjects over consecutive sessions. Number of nicotine injections/session significantly decreased as dose/injection increased and the number of self-administered nicotine injections was significantly greater than the number of self-administered saline injections across conditions. When FR value was progressively increased over sessions, response rates for nicotine, but not saline, injections increased, with maximal rates at the highest FR values. Rates of responding and injections/session were markedly and significantly higher for nicotine than for saline at FR values of 200 and above. Subjects rated effects of nicotine as both significantly more positive and more negative than saline placebo, with positive ratings significantly higher than negative ratings. Nicotine functioned as a prototypic drug of abuse, serving as an effective reinforcer of intravenous drug-taking behavior in human cigarette smokers. Subjects adjusted their responding to response requirements in a way that maintained relatively constant levels of nicotine injections per session.


Costing the components of pain management: analysis of Trans-Tasman Radiation Oncology Group trial (TROG 96.05): one versus five fractions for neuropathic bone pain.
Bone metastases causing neuropathic pain (NBP) have traditionally been treated with fractionated radiotherapy (RT). A recently reported randomised Trans-Tasman Radiation Oncology Group trial (TROG 96.05) supports this approach in many cases [Roos DE, Turner SL, O'Brien PC et al. Randomised trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05). Radiother Oncol 2005;75:54-63]. This study sought to compare costs to the Australian health-care system for patients receiving 1 versus 5 fractions for NBP. The RT and medication costs for 245 patients treated on TROG 96.05 were determined from trial data out to 3 months from RT. Admission costs and causes were derived from hospital records. RT costs (including re-treatments) were calculated to be 222 and 724 Australian dollars (A dollars) per patient for the 8 Gy/1 and 20 Gy/5 arms, respectively. This difference increased when analgesics (A dollars 192 versus A dollars 229) and related hospital admissions (A dollars 1,411 versus A dollars 1,893) were considered. Sensitivity analysis demonstrated an incremental cost saving of between A dollars 795 and A dollars 1,468 for single fraction RT. Admission rates had the strongest potential to distort cost differences. Clinical outcomes are paramount in choice of fractionation scheme but are optimally considered in the light of economic implications. Overall cost differences between fractionation schedules may vary greatly from those incurred by the RT treatment centre alone. Ideally, such economic evaluations should be planned at the outset of a trial.


Outpatient mental health service use in major trauma survivors: A population-based cohort study from Ontario, Canada.
Mental health is recognized as an important outcome in major trauma survivors. There are limited data on how and when survivors access mental health services. Our objectives were to determine the frequency, timing, and factors associated with outpatient mental health service utilization in major trauma survivors. We conducted a population-based cohort study using linked administrative data on patients treated for major trauma in Ontario between 2009 and 2017. All trauma survivors were included in the cohort, and composite rates of outpatient mental health service use (family doctor, psychiatrist, or emergency department visits) were compared in the 3 years preinjury and postinjury. We used an exposure crossover study design and negative binomial regression with generalized estimating equations for the analysis. Multivariate logistic regression analyses were used to identify patient characteristics associated with mental health service use during the follow-up period. There were 37,260 patients included in the cohort, predominantly men (70.8%) from urban areas (84.8%) suffering blunt trauma (89.7%). Among the patients, 47.4% used mental health services during the preinjury period and 61.8% during the postinjury period (absolute increase of 14.4%). Compared with the 3 years preinjury, the rate of mental health service use increased by 80% (rate ratio, 1.8; 95% confidence interval, 1.75-1.77) in the 3 years following injury. Most survivors (62.2%) used services within the first year following discharge. Postinjury mental health service use (adjusted odds ratio, 3.4; 95% confidence interval, 2.2-3.7) was most strongly associated with preinjury mental health service use. Preinjury and postinjury outpatient mental health service use is common in trauma patients, with preinjury service use predictive of ongoing service use. Mental health concerns should be an expected outcome of major trauma and efforts made to implement and expand access to services for injury survivors across trauma systems. Therapeutic/Care Management; Level IV.


Statistical quality control procedures.
The right quality control (QC) should ensure the detection of important errors. Statistical QC (SQC) should be included in all QC plans. The Clinical and Laboratory Standards Institute (CLSI) C24A3 provides guidance for the application of SQC in medical laboratories. It describes a QC planning process and provides an SQC selection tool that relates the sigma-metric of a testing process to the medically important systematic error and the rejection characteristics of different SQC procedures. Once the right SQC has been selected, the laboratory must implement SQC right. CLSI C24A3 also provides guidance for establishing run length and control limits.


Refusal of treatment for acute leukemia in pregnancy: a case report.
Acute leukemia is rare in pregnancy. The importance of promptly diagnosing and treating this disease in pregnancy stems from its life-threatening potential, both to the mother and fetus. We report a case of relapse of acute myeloid leukemia at 23 weeks of pregnancy in a 24-year-old Albanian woman. Our patient categorically refused chemotherapy treatment, and in her 35th week of gestation, severe hemorrhagic diathesis rapidly developed. The manifestation and course of this life-threatening complication posed therapeutic challenges for the attending medical team. Based both on our experience and the results of other gynecological studies, there exists a strong indication that the earlier a patient's chemotherapy treatment begins, the better the maternal outcome. We support chemotherapy for patients who are pregnant presenting with such illness. The present case report testifies that refusal of chemotherapy by such patients is a high-risk decision.


Total saponins of panax ginseng inhibiting human endothelium cells' damages induced by angiotensin II via AT1 receptor.
To investigate the effect and mechanism of total saponins of panax ginseng (TSPG) on the damages of endothelium cells induced by Angiotensin II (AngII). Fifty SD rats were randomly divided into three groups: sham, AngII, and AngII+TSPG. The osmotic pumps with AngII were embedded in the backs of the animals in AngII and AngII+TSPG group, and TSPG was delivered through the gastric tube in AngII+TSPG group. The plasma tumor necrosis factor-α (TNF-α) and nitric oxide (NO) were measured by ELISA, and Human aortic endothelial cells (HAECs) were observed with scanning electron microscope (SEM). In addition, HAECs were treated with AngII and TSPG or Ang-(1-7), and the ECs were incubated with AngII for 30min, before with AT1 receptor antagonist (AT1RA) and TSPG. Tested were NAD(P)H oxidase subunit P22phox mRNA, intracellular reactive oxidative species (ROS), nuclear factor-κB (NF-κB) and vascular cell adhesion molecule-1(VCAM) expression. In the in vivo study, the plasma TNF-α increased significantly in AngII group when compared with the sham group, and decreased significantly in AngII+TSPG group. However, NO measurement produced opposite results. The surface of the thoracic aorta ECs desquamated in the AngII group, and most of them were restored in the AngII+TSPG group. In the in vitro study, TSPG reduced significantly the expressions of the NAD(P)H oxidize subunit P22phox, NF-κB and intracellular ROS production induced by AngII, and the inhibitory effects of TSPG were partially blocked by AT1 receptor antagonist. TSPG was found to be capable of preventing the damages of ECs induced by Ang II via AT1 receptor pathway.


Urinary tract infection after clean-contaminated pelvic surgery: a retrospective cohort study and prediction model.
Postoperative urinary tract infection (UTI) leads to increased patient morbidity and health care costs. A prediction model may identify patients at highest risk for UTI development. Our primary objective was to determine the rate of UTI in the first 6 weeks after benign gynecologic surgery. Our secondary objective was to identify risk factors and build a predictive model for postoperative UTI. We reviewed 310 patient records, which represent all patients who underwent clean-contaminated surgery at a tertiary center (2016-2017). UTI was defined as positive urine culture (> 100,000,000 CFU/l) in a symptomatic patient. Pre-, intra- and postoperative variables were collected. The relation between these variables and UTI was assessed through logistic regression. A clinical prediction model was built. Patients' mean age was 58.5 years and mean body mass index was 27.5 kg/m2. Most were inpatients (65.8%) and 269 had urogynecologic procedures, with the remainder undergoing pelvic surgery for other indications. The most common operation was vaginal reconstruction for prolapse (59.7%), associated with concomitant synthetic midurethral sling in 1/3 cases. Forty patients (12.9%) developed UTI. Multivariate prediction modeling showed increasing age (OR 1.33, CI 1.01-1.75), increasing number of procedures (OR 1.42, CI 1.14-1.78) and prolonged voiding dysfunction (OR 3.78, CI 1.66-8.60) to be significant UTI predictors. Urinary tract infection in the first 6 weeks after complex pelvic surgery is common. Our prediction model identifies that patients who are older women, have prolonged voiding dysfunction and have a greater number of concomitant pelvic floor surgeries have higher risk of postoperative UTI.


Enhanced consumer goal achievement through strengths-based group supervision.
This article seeks to enhance and support consumer-centered care in psychiatric rehabilitation through the use of strengths-based group supervision (SBGS). The article is based on social science research findings, 30 years of experience with the model, and the literature on supervision. Relevant findings from research on the model are included. SBGS is a promising approach for improving consumer goal achievement and centeredness. It warrants further implementation and research.


Hepatectomy in elderly patients: does age matter?
With the increase in average life expectancy in recent decades, the proportion of elderly patients requiring liver surgery is rising. The aim of the meta-analysis reported here was to evaluate the safety and efficacy of hepatectomy in elderly patients. An extensive electronic search was performed for relevant articles that compare the outcomes of hepatectomy in patients ≥70 years of age with those in younger patients prior to October 2012. Analysis of pooled data was performed with RevMan 5.0. Twenty-eight observational studies involving 15,480 patients were included in the analysis. Compared with the younger patients, elderly patients experienced more complications (31.8 vs 28.7 %; P = 0.002), mainly as a result of increased cardiac complications (7.5 vs 1.9 %; P < 0.001) and delirium (11.7 vs 4.5 %; P < 0.001). Postoperative major surgical complications (12.6 vs 11.3 %; P = 0.55) and mortality (3.6 vs 3.3 %; P = 0.68) were comparable between elderly and younger patients. For patients with malignancies, both the 5-year disease-free survival (26.5 vs 26.3 %; P = 0.60) and overall survival (39.5 vs 40.7 %; P = 0.29) did not differ significantly between the two groups. Postoperative major surgical complications, mortality, and long-term results in elderly patients seem to be comparable with those in younger patients, suggesting that age alone should not be considered a contraindication for hepatectomy.


Prey use of the fishing spider Dolomedes triton (Pisauridae, Araneae): an important predator of the neuston community.
Prey of feeding juvenile and adult Dolomedes triton (Walckenaer 1837) were sampled over two seasons on three small ponds in central Alberta, Canada. Prey were mainly insects active at the water surface with truly aquatic species making up about 14% of the diet. Throughout the season aquatic and semi-aquatic Heteroptera represented about 30% of the prey. Diptera and adult Odonata were also important prey items but their abundance in the diet was more variable seasonally. Of the 625 prey items recorded nearly 50% were represented by taxa taken no more than once by spiders in one of the five size classes (adult females, adult males, large, intermediate and small juveniles). Large spiders did not take the smallest prey available, although small and intermediate-sized spiders fed on nearly the full size range taken by larger spiders. Cannibalism was common, accounting for 5% of the observations, with females and large juveniles as the most frequently observed cannibals. We hypothesize that intraguild predation (including cannibalism) could be an important coevolutionary force structuring phenology, population dynamics and microhabitat use of the predatory guild of the neuston community.


Transfer of light-induced electron-spin polarization from the intermediary acceptor to the prereduced primary acceptor in the reaction center of photosynthetic bacteria.
In reaction centers and chromatophores of photosynthetic bacteria strong light-induced emissive ESR signals have been found, not only after a flash but also under continuous illumination. The signal, with g = 2.0048 and delta Hpp = 7.6 G, is only present under reducing conditions in material in which the primary acceptor, ubiquinone, U and its associated high-spin ferrous ion are magnetically uncoupled. its amplitude under continuous illumination is strongly dependent on light intensity and on microwave power. The emissive signal is attributed to the prereduced primary acceptor, U-, which becomes polarized through transfer of spin polarization by a magnetic exchange interaction with the photoreduced, spin polarized intermediary acceptor, I-. A kinetic model is presented which explains the observed dependence of emissivity on light intensity and microwave power. Applying this analysis to the light saturation data, a value of the exchange rate between I- and U- of 4.10(8) s-1 is derived, corresponding to an exchange interaction of 3--5 G.


Participation of GABAB Receptors of Parafacial Respiratory Group in the Regulation of Respiration in Rats.
The respiratory effects of microinjections of baclofen and 2-hydroxysaclofen into the parafacial respiratory group were studied in experiments on rats. It was shown that activation of GABAB receptors of the parafacial respiratory group suppressed external respiration due to a decrease in the tidal volume and inspiratory flow rate. In parallel, we observed a decrease in the amplitude and an increase in the duration of inspiratory bursts of the diaphragm. Injection of GABAB receptor blocker into the parafacial respiratory group increased pulmonary ventilation due to an increase in volumetric parameters of the inspiratory phase. This effect was accompanied by prolongation of expiration and lengthening of the intervals between the inspiratory bursts of the diaphragm. These results suggest that GABAB receptors of the parafacial respiratory group are an important element of the central mechanisms regulating the volumetric respiratory parameters and are involved in the regulation of the phases of the respiratory cycle.


A nystatin-resistant mutant of Rhodotorula gracilis. Transport properties and sterol content.
A nystatin-resistant mutant of Rhodotorula gracilis was obtained by treatment of the wild strain cells with N-methyl-N-nitro-N-nitrosoguanidine and selected on agar plates containing 150 micrograms nystatin/ml. Three important transport functions of the plasma membrane of mutant cells: the accumulation of monosaccharides, the generation and maintenance of the pH-gradient and of the membrane potential, as well as the cell respiration were insensitive to at least 10(-5) M nystatin. This concentration of nystatin inhibited completely all these processes in wild strain cells. Analysis of cellular sterols revealed a defect of ergosterol biosynthesis in the mutant, which was localized at the last oxidative step between 5,6-dihydroergosterol and ergosterol.


Is chronic pain a variant of depressive disease? The case of primary fibromyalgia syndrome.
The responses of 45 primary fibromyalgia syndrome (PFS) patients, 29 rheumatoid arthritis (RA) patients and 31 healthy non-pain controls (NC) on the Zung Self-Rating Depression scale were compared. No difference between the PFS and RA groups was found, although the former has no known organic pathology, unlike the latter. Therefore, the hypothesis that the presentation of chronic pain in the absence of a known organic pathology is a variant of 'depressive disease' was not supported in the case of PFS. However, a subgroup of PFS (28.6%) and RA (31.0%) patients appeared to be experiencing significant depressive symptomatology.


Virologic suppression and mortality of patients who migrate for HIV care in the province of British Columbia, Canada, from 2003 to 2012: a retrospective cohort study.
Migration among persons living with HIV (PLWH) seeking HIV care is common; however its effect on health outcomes in resource-rich settings is not well understood. We conducted a retrospective cohort study to quantify the extent to which PLWH are migrating for care within British Columbia (BC) and its association with virologic suppression and mortality. Eligible PLWH first initiated treatment in BC between 2003 and 2012 (N = 3653). Analyses were performed at the regional Health Authority (HA) level (N = 5). For privacy reasons, we kept the name of these HAs anonymous and we re-named these five regions as 1 to 5. PLWH were classified according to the HA where they resided and received HIV care. We calculated all-cause mortality rates, life expectancies (at age of 20 years), and in, out and net migration rates across HAs using different demographic methods. Virologic suppression (<50 copies/mL) was based on the last viral load available for each PLWH. We also calculated per-capita rates (per 100 PLWH ever on cART) for each HA by dividing the number of PLWH by the number of physicians attending this population. There is considerable heterogeneity in physician availability across all HAs, with per-capita rates (per 100 PLWH ever on cART) ranging from 2.2 (HA 1) to 12.7 (HA 3) based on the HA PLWH received care. We observed that in HAs 1, 4, and 5, between 4 and 10% of PLWH migrated to HA 3 (i.e. the largest urban center) to receive care, and for HA 2 this proportion increased to 21%. In HA 3, 77% of its PLWH residents remained in the same HA for their care. Migrating to a larger center for HIV care was not associated with higher rates of viral load suppression; it was significantly associated with lower mortality rates and higher life expectancies. A thorough understanding of the reason(s) for these significant migration rates across BC will be critical to inform resource allocation and optimize the impact of HIV treatment.


Thermal-responsive genetic and epigenetic regulation of DAM cluster controlling dormancy and chilling requirement in peach floral buds.
The Dormancy-associated MADS-box (DAM) gene cluster in peach serves as a key regulatory hub on which the seasonal temperatures act and orchestrate dormancy onset and exit, chilling response and floral bud developmental pace. Yet, how different temperature regimes interact with and regulate the six linked DAM genes remains unclear. Here, we demonstrate that chilling downregulates DAM1 and DAM3-6 in dormant floral buds with distinct patterns and identify DAM4 as the most abundantly expressed one. We reveal multiple epigenetic events, with tri-methyl histone H3 lysine 27 (H3K27me3) induced by chilling specifically in DAM1 and DAM5, a 21-nt sRNA in DAM3 and a ncRNA induced in DAM4. Such induction is inversely correlated with downregulation of their cognate DAMs. We also show that the six DAMs were hypermethylated, associating with the production of 24-nt sRNAs. Hence, the chilling-responsive dynamic of the different epigenetic elements and their interactions likely define distinct expression abundance and downregulation pattern of each DAM. We further show that the expression of the five DAMs remains steadily unchanged or continuously downregulated at the ensuing warm temperature after chilling, and this state of regulation correlates with robust increase of sRNA expression, H3K27me3 and CHH methylation, which is particularly pronounced in DAM4. Such robust increase of repressive epigenetic marks may irreversibly reinforce the chilling-imposed repression of DAMs to ensure flower-developmental programming free from any residual DAM inhibition. Taken together, we reveal novel information about genetic and epigenetic regulation of the DAM cluster in peach, which will be of fundamental significance in understanding of the regulatory mechanisms underlying chilling requirement and dormancy release, and of practical application for improvement of plasticity of flower time and bud break in fruit trees to adapt changing climates.


The experience of new nurses' early working life: Learning in a hospital care context - An interview study.
To explore how nurses during their early working life learn to provide high-quality care in relation to organisational prerequisites in a hospital setting. When nurses enter employment in contemporary hospital settings, they face multiple learning challenges. Organisational prerequisites that have been identified to affect their ability to learn to provide high-quality care are related to staffing turnovers, large patient groups and a lack of experienced staff to support their learning. Qualitative. The study was conducted between 2018 and 2019 at a medium-sized hospital in Sweden. Data from interviews with 10 nurses with fewer than two years' work experience were subjected to qualitative content analysis. The results describe the nurses' learning during their early working life in two categories: Performing tasks in relation to organisational prerequisites and Making use of clinical experiences to grasp the complexity of nursing care. The first theme reflected a learning process that was initially characterised by seeking confirmation and instructions from colleagues of how to act safely and by balancing the demands of time efficiency and sustaining patient safety. The second theme reflected that, after addressing organisational prerequisites, the nurses tried to understand and make use of clinical experiences to grasp the complexity of nursing care by encountering and processing clinical patient situations. The results of this study revealed that nurses' learning during early working life seemed to be primarily directed towards handling tasks, with sometimes limited opportunities to grasp the complexity of nursing care. Their learning depended largely on their own initiative and motivation and was strongly influenced by organisational prerequisites. The limited availability of experienced nurse colleagues and lack of time devoted for reflection needs to be dealt with to support nurses' learning.


Mechanical thrombectomy with second-generation devices for acute cerebral middle artery M2 segment occlusion: A meta-analysis.
The benefit of mechanical thrombectomy for an acute ischemic stroke involving M2 segment occlusion is not clear, especially when performed with second-generation thrombectomy devices. We reviewed the literature to investigate clinical outcomes and the rates of recanalization, symptomatic intracerebral hematoma, and mortality in mechanical thrombectomy performed using second-generation thrombectomy devices. We compared the outcomes between patients treated for M2 and M1 occlusions. Seven studies involving 805 patients with M2 thrombectomy were included in this meta-analysis. The functional independence rate 90 days after thrombectomy (modified Rankin Scale 0-2) was 59.3% (OR 1.81, 95% CI 1.74-1.88). The recanalization rate (thrombolysis in cerebral infarction 0-2) was 84.16% (OR 2.32, 95% CI 2.08-2.29). The symptomatic intracerebral hematoma rate was 4.9% (OR 1.05, 95% CI 1.03-1.09). The mortality was 7.7% (OR 1.08, 95% CI 1.03-1.13). The outcomes were better in patients with M2 occlusion than in those with M1 occlusion. In a subgroup analysis, we found that among patients with hypertension, mechanical thrombectomy achieved better functional outcomes and recanalization in M2 occlusion than M1 occlusion. Mechanical thrombectomy performed with second-generation thrombectomy devices for M2 occlusion can provide a good functional outcome as well as satisfying recanalization. Moreover, there was no significant difference in the symptomatic intracerebral hematoma and mortality rates, suggesting this procedure is as safe in M2 occlusion as in M1 occlusion.


Ovine pulmonary adenomatosis in Patagonia, Argentina.
An outbreak of pulmonary adenomatosis (OPA) occurred in sheep in Patagonia, Argentina's southernmost region. On the affected farm, nine animals died over a 6-month period with pulmonary lesions of OPA. In all cases, the histology of the lungs was characterized by proliferation of cuboideal and prismatic cells lining the alveoli. Inflammatory exudates and accumulation of alveolar macrophages were marked in most cases, but in six of the cases there was no excess fluid in the airways. The presence of the Jaagsiekte retrovirus was demonstrated in the lungs by immunocytochemistry and PCR. To the best of our knowledge, this is the first report of OPA in Patagonia.


Neutrophil function and diagnosis of pre-leukaemic states.
Haemopoietic dysplasia is a condition which often precedes the development of acute non-lymphocytic leukaemia. Before this event, however, patients are at risk from severe infections even in the absence of neutropenia. This paper describes 3 patients with haemopoietic dysplasias in whom neutrophil microbicidal activity was deficient in vitro. The important abnormality appeared to be defective release of myeloperoxidase into the phagocytic vacuole. Two of these patients suffered from numerous baterial infections.


[Bilateral desensitization in CRPS with allodynia of the hand : An innovative treatment approach in ergotherapy].
This article describes the case of a female patient with symptoms of complex regional pain syndrome (CRPS) of the right wrist and forearm. Ergotherapy of the affected hand (unilateral desensitization) showed little success and became impossible with increasing environmental temperature due to excessive pain. A physiological feedback via simultaneous treatment of the unaffected healthy arm (bilateral treatment approach) ultimately led to a clear decline of all CRPS symptoms.


Performance of ceftriaxone susceptibility testing on the Accelerate Pheno® system of ESBL-producing isolates.
The correlation of ceftriaxone nonsusceptibility and ESBL production was evaluated in 40 characterized isolates. Performance of ceftriaxone susceptibility testing on the Accelerate Pheno was evaluated and compared with reference broth microdilution in triplicate. The CLSI ESBL confirmatory test was also evaluated. Ceftriaxone categorical agreement of the Accelerate Pheno was 97.5% with 1 minor error. The ESBL confirmatory disk test resulted in 4 false-negatives and 1 false positive. The Accelerate Pheno provides an expedited and accurate method of ceftriaxone susceptibility testing allowing for optimization of antimicrobial regimens sooner. These data indicate that ESBL production has a high likelihood of ceftriaxone non-susceptibility.


Engineering of new graphene-based materials as potential materials to assist near-infrared photothermal therapy cancer treatment.
Photothermal therapy is an emerging method of cancer treatment in which tumors are ablated by heating agents using near-infrared light (700-1000 nm). A semiconductor with a band gap between 0.3-0.7 eV would therefore efficiently emit near-infrared light. The new "magic" material graphene has a band gap of zero, which is advantageous with regard to designing a new material with a suitable band gap for the emission of near infrared light. In our investigations, using the first principles density functional theory calculation method, we aimed to and successfully designed graphene-based materials with a direct band gap of 0.68 eV. They have the potential to be optimal and efficient near-infrared light sources, due to their narrow yet fitting band gap. The present results open up a new avenue for the application of graphene-based materials to assist in photothermal therapy.


Evaluation of criteria for the acceptance of bioanalytical data.
Results from bioanalytical analyses for registration of a new drug entity are used to define its pharmacokinetics and bioavailability/bioequivalence. Whilst analytical data may be derived from the application of a validated method, it is essential to apply mathematical criteria to its acceptance, in order that the analyst can be assured that the assay is performing within defined limits and to its validated specification. Parameters evaluated for acceptability are the batch calibration curve, the minimum quantifiable concentration and the quality control (QC) sample acceptability. Specifically, six QC samples per analytical batch are used, two samples at each of three concentrations. The rationale for the definition of these criteria is evaluated together with a consideration of their applications and limitations. The relevance and use of Shewhart and Cusum plots to monitor assay performance is illustrated.


Results of AIEOP LNH-97 protocol for the treatment of anaplastic large cell lymphoma of childhood.
Anaplastic large cell lymphoma (ALCL) represents approximately 15% of all pediatric non-Hodgkin lymphomas (NHL). It has distinct clinical features, including frequent involvement of extranodal sites and rare localization to the central nervous system (CNS). Despite varying treatment approaches the outcome of patients with ALCL has not significantly improved during the last two decades. From October 1997 to beginning of 2000, newly diagnosed ALCL patients were enrolled into AIEOP LNH-97 protocol for ALCL. Thereafter and until 2007, only CNS positive patients were included. AIEOP LNH-97 was based on the BFM-95 schema for ALCL and included six high-dose chemotherapy courses. CNS prophylaxis was obtained with one intrathecal injection of chemotherapy in each course, whereas treatment of CNS involvement included three intrathecal injections without irradiation. Thirty-two patients were eligible for the study. Lymph-node disease was the most frequent localization (69% of the cases), followed by mediastinal (25%), CNS (22%), bone marrow (16%), and skin (13%) involvement. Probabilities of overall survival (OS) and of event-free survival (EFS) at 5 years for the whole population were 87% (SE 6%) and 68% (SE 8%), respectively. This study confirmed that short pulse chemotherapy is an efficacious treatment option for first line therapy of pediatric ALCL, and that dose intensity may have some relevance for outcome, but not in all of the patients. Refinement and optimization of therapy strategies for ALCL may originate from a combination of clinical and biological prospective studies, as those in the pipeline of current international collaboration.


Estrogen synthetase in choriocarcinoma cell culture. Stimulation by dibutyryl cyclic adenosine monophosphate and theophylline.
The stimulation of estrogen biosynthesis by N6,O2'--dibutyryl adenosine 3':5'-cyclic monophosphate and theophylline dbT) in cultures of the JAr line of choriocarcinoma cells was investigated by measuring the specific activity and kinetic constants of estrogen synthetase (aromatase) in the various subcellular fractions after differential centrifugation of homogenized cells in isotonic sucrose. The low speed (900xg) pellet, from cells grown with or without dbT and homogenized in isotonic sucrose, contains the majority of the aromatase activity and the highest aromatase specific activity. The aromatase specific activity in the homogenate of cells grown with dbT and in the various subcellular fractions is 4- to 10-fold higher than in cells grown without dbT. The Vmax of androstenedione (4-androstene-3,17-dione) aromatization in homogenates from dbT-stimulated cells (6.9 pmol estrogen/min per mg protein) is significantly increased over that measured in the absence of dbT (1.5 pmol estrogen/min per mg protein); the Km values, however, are not significantly different (average of 43.8nM in dbT-stimulated fractions; 53.2nM in control fractions). These results suggest that the increased aromatase specific activity in dbT-stimulated cells results from an increase in amount of active enzyme, rather than from an increase in affinity of the enzyme for its substrate.


Transdiagnostic Motivational Enhancement Therapy to Reduce Treatment Attrition: Use in Emerging Adults.
Improving outcomes of youth with mental health (MH) needs as they transition into adulthood is of critical public health significance. Effective psychotherapy MH treatment is available, but can be effective only if the emerging adult (EA) attends long enough to benefit. Unfortunately, completion of psychotherapy among EAs is lower than for more mature adults (Edlund et al., 2002; Olfson, Marcus, Druss, & Pincus, 2002). To target the high attrition of EAs in MH treatment, investigators adapted a developmentally appropriate brief intervention aimed at reducing treatment attrition (TA) in psychotherapy and conducted a feasibility study of implementation. The intervention employs motivational interviewing strategies aimed at engaging and retaining EAs in outpatient MH treatment. Motivational enhancement therapy for treatment attrition, or MET-TA, takes only a few sessions at the outset of treatment as an adjunct to usual treatment. Importantly, it can be used for TA with psychotherapy for any MH condition; in other words, it is transdiagnostic. This article presents the first description of MET-TA, along with a case example that demonstrates important characteristics of the approach, and then briefly describes implementation feasibility based on a small pilot randomized controlled trial.


Of Brains and Blood: Developmental Origins of Glioma Diversity?
The multiple cell types of brain and blood arise from pluripotent stem cells via progressively more committed downstream progenitors. In this issue of Cancer Cell, Alcantara Llaguno and colleagues show that identical genetic drivers give rise to distinct glioma subtypes within differentially committed neural progenitors-a paradigm well established for leukemias.


Puerol and pueroside derivatives from Pueraria lobata and their anti-inflammatory activity.
Five undescribed puerols and puerosides and three known analogues were obtained from the roots of Pueraria lobata. Their structures were determined by comprehensive analysis of spectroscopic data and chemical methods. Since puerol D and puerol C were racemic compounds, resolved into their enantiomers, and their absolute configurations were determined by experimental and calculated ECD spectra. Six of the isolates were evaluated for their inhibitory activities on NO generation and the expression of inflammatory factors in the LPS-stimulated RAW 264.7 macrophage cells. The results showed that (S)-puerol C, (R)-puerol C, isokuzubutenolide A and kuzubutenolide A significantly decreased the NO production (IC50 values in the range of 16.87-39.95 μM). Meanwhile, (S)-puerol C, isokuzubutenolide A and kuzubutenolide A also reduced the mRNA expression of inflammatory factors (TNF-α, IL-1β and IL-6).


Early snowmelt significantly enhances boreal springtime carbon uptake.
We determine the annual timing of spring recovery from space-borne microwave radiometer observations across northern hemisphere boreal evergreen forests for 1979-2014. We find a trend of advanced spring recovery of carbon uptake for this period, with a total average shift of 8.1 d (2.3 d/decade). We use this trend to estimate the corresponding changes in gross primary production (GPP) by applying in situ carbon flux observations. Micrometeorological CO2 measurements at four sites in northern Europe and North America indicate that such an advance in spring recovery would have increased the January-June GPP sum by 29 g⋅C⋅m-2 [8.4 g⋅C⋅m-2 (3.7%)/decade]. We find this sensitivity of the measured springtime GPP to the spring recovery to be in accordance with the corresponding sensitivity derived from simulations with a land ecosystem model coupled to a global circulation model. The model-predicted increase in springtime cumulative GPP was 0.035 Pg/decade [15.5 g⋅C⋅m-2 (6.8%)/decade] for Eurasian forests and 0.017 Pg/decade for forests in North America [9.8 g⋅C⋅m-2 (4.4%)/decade]. This change in the springtime sum of GPP related to the timing of spring snowmelt is quantified here for boreal evergreen forests.


[Comparative Estimate of the Sheep Breed Gene Pools using ISSR Analysis].
Using the ISSR-PCR technique, the genetic structure of nine sheep breeds (Ovis aries) bred on the territories of Russia and Mongolia was examined. Species-specific and breed-specific DNA fragments were identified. For the first time, data on the genetic diversity of Telengit and Buubey sheep breeds were obtained. The main parameters of the genetic diversity and the breed structure were assessed, and the phylogenetic relationships and genetic distances between the studied breeds were determined. Using the method of hierarchical frequency averaging, the prototypal sheep gene pool was reconstructed. The three-tiered analysis of diversity based on the ISSR fingerprinting data showed that 15.8% of variability was found between the breeds, 31.4% of variability was found between the populations within the breeds, and the diversity among the individuals within the populations constituted 52.8%.


Comparison of mitral inflow and superior vena cava Doppler velocities in chronic obstructive pulmonary disease and constrictive pericarditis.
This study was conducted to determine whether Doppler recording of superior vena cava flow velocities can differentiate chronic obstructive pulmonary disease from constrictive pericarditis in patients with a respiratory variation of > or = 25% in mitral inflow E velocity. Although respiratory variation (> or = 25%) in mitral E velocity is the main diagnostic criterion for constrictive pericarditis by Doppler echocardiography, it can also be present in chronic obstructive pulmonary disease. Because the respiratory variation is due to increased change in intrathoracic pressure with respiration in chronic obstructive pulmonary disease, and to dissociation of intrathoracic-intracardiac pressure changes in constriction, it was hypothesized that the Doppler flow velocity pattern in the superior vena cava (affected by intrathoracic pressure) would be different in these two conditions. Pulsed-wave Doppler recording of mitral and superior vena cava flow velocities in 20 patients with chronic obstructive pulmonary disease who had > or = 25% respiratory variation in mitral E-wave velocity were compared with those of 20 patients who had surgically proved constrictive pericarditis. Constrictive pericarditis and chronic obstructive pulmonary disease had similar respiratory variation in mitral E velocity (41% versus 46%). In the latter, the E/A ratio was lower (inspiration, 0.8+/-0.3 versus 1.5+/-0.7 [p < 0.0001]; expiration, 1.0+/-0.3 vs. 1.9+/-0.7 [p < 0.0001]) and deceleration time longer (inspiration, 198+/-53 ms versus 137+/-32 ms; expiration, 225+/-43 ms vs. 161+/-33 ms [p < 0.0001]). Inspiratory superior vena cava systolic forward flow velocity was significantly higher in chronic obstructive pulmonary disease (72.9+/-22.6 cm/s versus 36.2+/-9.3 cm/s, p < 0.0001), while expiratory systolic forward flow velocity was similar. Hence, there was a significantly greater respiratory variation in superior vena cava systolic forward flow velocity in chronic obstructive pulmonary disease without an overlap with constrictive pericarditis (39.5+/-18.8 cm/s vs. 4.2+/-3.4 cm/s, p < 0.0001). Despite a similar respiratory variation in mitral E wave velocities, mitral inflow variables in chronic obstructive pulmonary disease are less restrictive compared with those in constrictive pericarditis. More importantly, patients with chronic obstructive pulmonary disease show a marked increase in inspiratory superior vena cava systolic forward flow velocity, which is not seen in patients with constrictive pericarditis.


Cancer screening: evidence and practice in Europe 2008.
We examine the theoretical basis of screening, followed by an evaluation of screening initiatives from a population health perspective and a discussion of the organisation of mass screening programmes. Evidence for the effectiveness of screening by primary site from both randomised trials and evaluation of service screening is summarised and the existing cancer screening programmes in the European Union are described. Sufficient evidence from several randomised trials to demonstrate mortality reduction exists for breast cancer and colorectal cancer screening. At least one trial has shown efficacy with a mortality end-point in screening for hepatocellular carcinoma and oral cancer. Randomised trials have demonstrated a lack of mortality effect in lung cancer screening based on chest X-ray and sputum cytology. Despite the lack of randomised trials, population screening for cervical cancer with cytological smears has been convincingly shown to reduce cervical cancer incidence and mortality.


Hybrid-DIA: intelligent data acquisition integrates targeted and discovery proteomics to analyze phospho-signaling in single spheroids.
Achieving sufficient coverage of regulatory phosphorylation sites by mass spectrometry (MS)-based phosphoproteomics for signaling pathway reconstitution is challenging, especially when analyzing tiny sample amounts. To address this, we present a hybrid data-independent acquisition (DIA) strategy (hybrid-DIA) that combines targeted and discovery proteomics through an Application Programming Interface (API) to dynamically intercalate DIA scans with accurate triggering of multiplexed tandem mass spectrometry (MSx) scans of predefined (phospho)peptide targets. By spiking-in heavy stable isotope labeled phosphopeptide standards covering seven major signaling pathways, we benchmark hybrid-DIA against state-of-the-art targeted MS methods (i.e., SureQuant) using EGF-stimulated HeLa cells and find the quantitative accuracy and sensitivity to be comparable while hybrid-DIA also profiles the global phosphoproteome. To demonstrate the robustness, sensitivity, and biomedical potential of hybrid-DIA, we profile chemotherapeutic agents in single colon carcinoma multicellular spheroids and evaluate the phospho-signaling difference of cancer cells in 2D vs 3D culture.


Common occurrence of Cryptosporidium hominis in horses and donkeys.
Extensive genetic variation is observed within the genus Cryptosporidium and the distribution of Cryptosporidium species/genotypes in humans and animals appears to vary by geography and host species. To better understand the genetic diversity of Cryptosporidium spp. in horses and donkeys, we characterized five horse-derived and 82 donkey-derived Cryptosporidium isolates from five provinces or autonomous regions (Sichuan, Gansu, Henan, Inner Mongolia and Shandong) in China at the species/genotype and subtype levels. Three Cryptosporidium species/genotypes were identified based on the analysis of the SSU rRNA gene, including Cryptosporidium parvum (n=22), the Cryptosporidium horse genotype (n=4), and Cryptosporidium hominis (n=61). The identification of C. hominis was confirmed by sequence analysis of the HSP70 and actin genes. Subtyping using sequence analysis of the 60kDa glycoprotein gene identified 21 C. parvum isolates as subtype IIdA19G1, the four horse genotype isolates as subtypes VIaA15G4 (n=2) and VIaA11G3 (n=2), and the 61 C. hominis isolates as IkA16G1 (n=59) and IkA16 (n=2). The common finding of C. hominis reaffirms the heterogeneity of Cryptosporidium spp. in horses and donkeys and is possibly a reflection of endemic transmission of C. hominis in these animals. Data of the study suggest that horses and donkeys as companion animals may potentially transmit Cryptosporidium infections to humans.


High speed single nucleotide polymorphism typing of a hereditary haemochromatosis mutation with capillary array electrophoresis microplates.
A single nucleotide polymorphism (SNP) typing assay is developed and evaluated on a microfabricated capillary array electrophoresis system. Using fluorescently labeled allele-specific primers, the S65C (193A-->T) substitution associated with hereditary haemochromatosis in the HFE gene is genotyped. The covalently labeled polymerase chain reaction (PCR) products are separated on a microfabricated radial capillary array electrophoresis microplate using nondenaturing gel media in under two minutes. Detection is accomplished with a laser-excited rotary confocal scanner. The Rox-labeled A-allele specific amplicon (211 bp) is differentiated from the R110-labeled T-allele specific amplicon (201 bp) by both size and color. This study demonstrates the feasibility of using allele-specific PCR with covalently labeled primers for high speed fluorescent SNP typing on microfabricated radial capillary array electrophoresis microplates.


Treatment trajectories of patients with End Stage Kidney Disease
On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of trajectory of ESKD patients, the following key messages were retained. Apart from a few rare, absolute or relative contraindications, till date, there is no medical consensus on the indications of one treatment modality as compared to another, and therefore, no recommendations allowing defining criteria for guiding patients, based on their characteristics, to a technique/treatment modality. In addition, the patients' choices and their changing needs over time must be taken into account. Thus, due to the limitations of each of these modalities, a good number of patients with stage 5 renal failure treated with kidney replacement therapy will move between these different modalities. For many years, the REIN registry has endeavoured to represent the patient flows between the different treatment modalities. In order to better understand and then optimise the trajectories followed by patients who have reached stage 5 of their chronic renal failure, it was necessary to develop tools to model these complex trajectories where the treatment modalities are considered as complementary.


A genome-wide structure-based survey of nucleotide binding proteins in M. tuberculosis.
Nucleoside tri-phosphates (NTP) form an important class of small molecule ligands that participate in, and are essential to a large number of biological processes. Here, we seek to identify the NTP binding proteome (NTPome) in M. tuberculosis (M.tb), a deadly pathogen. Identifying the NTPome is useful not only for gaining functional insights of the individual proteins but also for identifying useful drug targets. From an earlier study, we had structural models of M.tb at a proteome scale from which a set of 13,858 small molecule binding pockets were identified. We use a set of NTP binding sub-structural motifs derived from a previous study and scan the M.tb pocketome, and find that 1,768 proteins or 43% of the proteome can theoretically bind NTP ligands. Using an experimental proteomics approach involving dye-ligand affinity chromatography, we confirm NTP binding to 47 different proteins, of which 4 are hypothetical proteins. Our analysis also provides the precise list of binding site residues in each case, and the probable ligand binding pose. As the list includes a number of known and potential drug targets, the identification of NTP binding can directly facilitate structure-based drug design of these targets.


Unusual intermolecular "through-space" j couplings in p-se heterocycles.
Solid-state NMR spectra of new P-Se heterocycles based on peri-substituted naphthalene motifs show the presence of unusual J couplings between Se and P. These couplings are between atoms in adjacent molecules and occur "through space", rather than through conventional covalent bonds. Experimental measurements are supported by relativistic DFT calculations, which confirm the presence of couplings between nonbonded atoms, and provide information on the pathway of the interaction. This observation improves the understanding of J couplings and offers insight into the factors that affect crystal packing in solids, for future synthetic exploitation.


Transperitoneal vs extraperitoneal approach for aortic sentinel node detection in endometrial cancer.
Although the sentinel lymph node technique in endometrial cancer is currently replacing pelvic and aortic lymphadenectomy for the evaluation of lymph node status in endometrial cancer, its performance is not yet standardized. This study aimed to describe the detection rates and locations of aortic sentinel lymph node detection after dual cervical and fundal indocyanine green injection in patients with endometrial cancer, using the transperitoneal and extraperitoneal approaches. Between June 26, 2014 and December 31, 2019, 278 patients underwent laparoscopic surgery for endometrial cancer at our institution. In all cases, we performed sentinel lymph node biopsy with dual cervical and fundal indocyanine green injection, and back-up lymphadenectomy in high-risk cases. A post hoc analysis was performed to evaluate differences between the transperitoneal and extraperitoneal approach to aortic sentinel lymph nodes. The detection rates were as follows: overall detection rate: 93.2% (259/278); pelvic detection rate: 90.3% (251/278); bilateral pelvic detection rate: 68.0% (189/278); aortic detection rate: 66.9% (186/278); and isolated aortic detection rate: 2.88% (8/278). Transperitoneal and extraperitoneal aortic detection rates were similar (65.0% and 69.6%, respectively), with no significant differences (P=.441). Isolated aortic metastases were similar in both groups (2% vs 4.7%, respectively; P=.185). The laterality of aortic sentinel lymph node detection was influenced by the surgical approach (P=.002), but not its location above or below the inferior mesenteric artery (P=.166 and P=.556, respectively). The detection rates at the aortic level were similar between the transperitoneal and extraperitoneal approaches, with no impact on subsequent pelvic detection. The transperitoneal approach detected more laterocaval, precaval, and interaortocaval nodes, whereas the extraperitoneal approach detected more preaortic and left lateroaortic nodes.


The Impact of Previous History of Bariatric Surgery on Outcome of COVID-19. A Nationwide Medico-Administrative French Study.
To determine the risk of invasive mechanical ventilation and death in obese individuals with a history of bariatric surgery (BS) admitted for COVID-19. All obese inpatients recorded during a hospital stay by the French National Health Insurance were included, and their electronic health data were reviewed retrospectively. Patients who had undergone bariatric surgery comprised the BS group and patients with obesity but no history of BS served as controls. The primary outcome was COVID-19-related death and the secondary outcome was the need for invasive mechanical ventilation. 4,248,253 obese individuals aged 15-75 years were included and followed for a mean observation time of 5.43 ± 2.93 years. 8286 individuals with a previous diagnosis of obesity were admitted for COVID-19 between January 1 and May 15, 2020. Of these patients, 541 had a history of BS and 7745 did not. The need for invasive mechanical ventilation and death occurred in 7% and 3.5% of the BS group versus 15% and 14.2% of the control group, respectively. In logistic regression, the risk of invasive mechanical ventilation was independently associated with increasing age, male sex, and hypertension, and mortality was independently associated with increasing age, male sex, history of heart failure, cancer, and diabetes, whereas BS had an independent protective effect. Two random exact matching tests confirmed the protective effect of BS. This nationwide study showed that BS is independently associated with a reduced risk of death and invasive mechanical ventilation in obese individuals with COVID-19.


Joint attention: inferring what others perceive (and don't perceive).
Research has shown that observers automatically align their attention with another's gaze direction. The present study investigates whether inferring another's attended location affects the observer's attention in the same way as observing their gaze direction. In two experiments, we used a laterally oriented virtual human head to prime one of two laterally presented targets. Experiment 1 showed that, in contrast to the agent with closed eyes, observing the agent with open eyes facilitated the observer's alignment of attention with the primed target location. Experiment 2, where either sunglasses or occluders concealed the agent's eye direction, showed that only the agent with the sunglasses facilitated the observer's alignment of attention with the target location. Taken together, the data demonstrate that head orientation alone is not sufficient to trigger a shift in the observer's attention, that gaze direction is crucial to this process, and that inferring the region to which another person is attending does facilitate the alignment of attention.


ONLAY VERSUS SUBLAY TECHNIQUES FOR INCISIONAL HERNIA REPAIR: 30-DAY POSTOPERATIVE OUTCOMES.
The development of an incisional hernia is a common complication following laparotomy. It also has an important economic impact on healthcare systems and social security budget. The mesh reinforcement of the abdominal wall was an important advancement to increase the success of the repairs and reduce its long-term recurrence. The two most common locations for mesh placement in ventral hernia repairs include the premuscular (onlay technique) and retromuscular planes (sublay technique). However, until now, there is no consensus in the literature about the ideal location of the mesh. The aim of this study was to compare the two most common incisional hernia repair techniques (onlay and sublay) with regard to the complication rate within the first 30 days of postoperative care. This study analyzes 115 patients who underwent either onlay or sublay incisional hernia repairs and evaluates the 30-day postoperative surgical site occurrences and hernia recurrence for each technique. We found no difference in the results between the groups, except in seroma formation, which was higher in patients submitted to the sublay technique, probably due to the lower rate of drain placement in this group. Both techniques of mesh placement seem to be adequate in the repair of incisional hernias, with no major difference in surgical site occurrences.


Inhibition of the microsomal N-hydroxylation of 2-amino-6-nitrotoluene by a metabolite of methimazole.
Inhibition studies were used to investigate the identity of the microsomal enzyme(s) responsible for the NADPH-dependent N-hydroxylation of 2-amino-6-nitrotoluene. The N-hydroxylation reaction was inhibited by several cytochrome P-450 inhibitors as well as by methimazole, a substrate for flavin-containing monooxygenase. Heat inactivation of flavin-containing monooxygenase had no effect on the rate of the reaction but abolished the inhibition by methimazole. These results indicate that the flavin-containing monooxygenase-mediated metabolism of methimazole produced an inhibitor of the cytochrome P-450-catalyzed N-hydroxylation reaction. When glutathione was included in the incubation the inhibition by methimazole was abolished, presumably due to the reduction of oxygenated metabolites of methimazole. These results show that methimazole inhibition does not necessarily implicate flavin-containing monooxygenase in microsomal N-hydroxylation reactions.


Lignin-derived sulfonate base metal-free N, S co-doped carbon microspheres doped with different nitrogen sources as catalysts for oxygen reduction reactions.
The oxygen reduction reaction (ORR) is an important step in the widespread application of metal-air batteries, so it is necessary to study and develop low-cost and efficient metal-free carbon-based catalysts to catalyze the ORR reaction. Heteroatomic doping, especially N and S co-doped carbon materials, has received much focus as a promising ORR catalyst. Meanwhile, the lignin material has high carbon content, wide source, and low price, and has wide application prospects for the preparation of carbon material catalysts. Here we report a hydrothermal‑carbonation preparation method for the synthesis of carbon microspheres by utilizing lignin derivatives as carbon precursors. And a variety of N, S co-doped carbon microsphere materials were prepared by adding different nitrogen sources (urea, melamine, NH4Cl) to the microspheres. The N, S co-doped carbon microspheres (NSCMS-MLSN) catalysts achieved with NH4Cl as the nitrogen source displayed superior RR catalytic activity with high half-wave potential (E1/2 = 0.83 V vs. RHE) and current density (JL = 4.78 mA cm-2). This work provides some references on the method of preparing carbon materials co-doped with N and S and the choice of nitrogen sources.


Anterior chamber tube shunt to an encircling band in the treatment of neovascular glaucoma.
A new procedure for neovascular glaucoma that has reduced intraocular pressure (IOP) significantly and has caused relatively few postoperative complications is introduced. Aqueous is shunted to the reservoir of an encircling no. 20 silicone band from which fluid is postulated to diffuse into the orbit. The anterior chamber tube shunt to an encircling band (ACTSEB) procedure was conducted in 19 eyes with neovascular glaucoma. After surgery 18 of the 19 eyes (95%) followed for periods ranging between five and 26 months (mean: 59 weeks) had controlled IOP using less than or equal to 20 mm Hg as normal, and one eye had partial control (eye 9) at 26 mm Hg. Despite the preoperative use of atropine sulfate, timolol maleate, acetazolamide, and 20% mannitol, the patients' average preoperative IOP was 54.1 mm Hg. After surgery the average IOP fell, dramatically, to 16.2 mm Hg. The mean change in IOP was 37.9 +/- 9.8 (SD). This change is statistically significant by the paired t-test, P less than 0.01. Minimal postoperative medications were required for pressure control. Postoperative complications included hyphema (21%), prolonged flat chamber (74%), localized peripheral lens opacity (5%), localized corneal opacity (5%), and possible acceleration of progressive cataract formation (25%). Results of current surgical procedures used to manage neovascular glaucoma are compared to the ACTSEB results.


Resting metabolic connectivity in prodromal Alzheimer's disease. A European Alzheimer Disease Consortium (EADC) project.
We explored resting-state metabolic connectivity in prodromal Alzheimer's disease (pAD) patients and in healthy controls (CTR), through a voxel-wise interregional correlation analysis of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) by means of statistical parametric mapping. Baseline 18F-fluorodeoxyglucose-positron emission tomography of 36 patients with amnestic mild cognitive impairment who converted to Alzheimer's disease (AD) dementia after an average time of 2 years (pAD) and of 105 CTR were processed. The area of hypometabolism in pAD showed less metabolic connectivity in patients than in CTR (autocorrelation and correlation with large temporal and frontal areas, respectively). pAD patients showed limited correlation even in selected nonhypometabolic areas, including the hippocampi and the dorsolateral prefrontal cortex (DLFC). On the contrary, in CTR group correlation was highlighted between hippocampi and precuneus/posterior cingulate and frontal cortex, and between dorsolateral prefrontal cortex and caudate nuclei and parietal cortex. The reduced metabolic connections both in hypometabolic and nonhypometabolic areas in pAD patients suggest that metabolic disconnection (reflecting early diaschisis) may antedate remote hypometabolism (early sign of synaptic degeneration).


Rns, a virulence regulator within the AraC family, requires binding sites upstream and downstream of its own promoter to function as an activator.
Strains of enterotoxigenic Escherichia coli that express CS1 and CS2 pili require the transcriptional activator Rns, a member of the AraC family, for the expression of the pilin genes. Rns is also an activator of its own expression. However, the arrangement of its binding sites near its own promoter is unusual for a prokaryotic activator. Most activators have at least one binding site 30-80 nucleotides upstream of the transcription start site, but Rns has a single upstream binding site centred at -227. Rns also has two binding sites downstream of the transcription start site centred at +43 and +82, a region generally thought to be reserved for repressors. In vitro, the binding of a MBP::Rns fusion protein to each of these sites facilitates the binding of RNA polymerase to the rns promoter and the formation of an open complex. In vivo, the upstream binding site and one downstream site are required for Rns-dependent activation of its promoter despite the atypical location of these binding sites for an activator. This suggests that Rns may represent a new class of prokaryotic activators.


A new approach and first steps to strengthen trauma management and road safety in North Vietnam.
In Vietnam, the number of road traffic accidents increased dramatically which is a major threat for the national health system. Reliable data on the magnitude of traffic accidents as well as the current management of victims is missing. Our multistep international cooperation project aims to (1) identify local needs and knowledge related to trauma management, to (2) assess basic behavioural patterns and attitudes of road users in order to (3) establish a school-based educational programme and trauma courses for doctors. As part of a European Union co-financed cooperation, two European and one Vietnamese university set up three action lines (Trauma and Emergency Courses, school-based education programs, public awareness campaigns). Specific contents of the activities were derived from a literature search, a questionnaire pilot-study and by panel consensus technique. After adjustment to local capabilities (equipment, infrastructure, etc.) these were implemented within a professional network of hospitals, schools, public and media institutions.The literature research and questionnaire results from 1 000 young road users indicates that for pedestrian and two-wheelers accidents, low compliance with traffic regulations and high prevalence of risk-taking behaviour dominate Vietnam's road traffic environment. A school-based educational program (4 hrs/month) was set up using teachers who were trained on road safety issues. Also, major parts of the public awareness campaigns (i.e. broadcasts, media conferences) reflected these topics. From panel discussions and Delphi-technique, diagnosis and early treatment of severe head trauma and internal haemorrhage were identified as topics of highest interest for doctors therefore representing key topics of the Trauma and Emergency Courses. Knowledge on behaviour and attitudes of road users in Vietnam as well as on local infrastructure and effective networks is essential to establish sustainable and effective countermeasures. Our approach might serve as guideline for future small scale projects as it proved to be feasible, cost-effective but provided scientific base for immediate on spot activities.


"INSIDE" Project on Sexual Health in Spain: Sexual Life During the Lockdown Caused by COVID-19.
The COVID-19 pandemic is becoming a major hazard to public health worldwide. This is causing a significant impact on life and physical health, as well as on the psychological well-being of the general population. Since the emotional distress and the social restrictions caused by this epidemic, it must be expected that its impact will also extend to sexual health. The purpose of this study, the first including a large sample of the Spanish general population, was to analyze sexual behavior during the 99 days of confinement in Spain (INSIDE Project). One thousand four hundred forty-eight Spanish people, between 18 and 60 years old, were evaluated through an online survey during April 2020. The variables analyzed were the physical and social environment during confinement, sexual desire, type of sexual activity, masturbation, sexual intercourse, online sexual activity, general sexual frequency, sexual fantasies, degree of self-control over sexual drive, sexual abuse, general impact of confinement on sexuality, and emotional mood. Confinement has affected the sexual life of half of the Spanish population (47.7%), especially women. Those who reported a worsening of their sexual life are almost three times more (37.9%) than those who reported an improvement (14.4%). Different factors have been significant predictors of the positive or negative evaluation about the impact of this confinement on sexual life, such as gender, couple life, privacy, stress level, and the perception of confinement as unbearable. These results have important implications for the public health and more especially sexual health of the Spanish population.


Co-use of cigarettes and cannabis among people with HIV: Results from a randomized controlled smoking cessation trial.
People with HIV (PWH) who smoke cigarettes have lower cessation rates than the general population. This study investigated whether changes in cannabis use frequency impedes cigarette cessation among PWH who are motivated to quit. Between 2016-2020, PWH who smoked cigarettes were enrolled in a randomized controlled trial for cigarette cessation. Analyses were limited to PWH who reported on their past 30-day (P30D) cannabis use during four study visits (baseline, 1-month, 3-month, and 6-month) (N=374). Descriptive statistics and multivariable logistic regression were used to evaluate changes in cannabis use frequency from baseline to 6 months and associations with cigarette abstinence at 6 months among PWH who reported no use during all four visits (n=176), as well as those who reported use during at least one visit and who increased (n=39), decreased (n=78), or had no change (n=81) in use frequency. Among those who reported cannabis use during at least one visit (n=198), at baseline, 18.2% reported no use. At 6 months, 34.3% reported no use. Controlling for covariates, increased cannabis use frequency from baseline was associated with reduced odds of cigarette abstinence at 6 months versus decreased use frequency (aOR=0.22, 95% CI=0.03, 0.90) or no use at either time-point (aOR=0.25, 95% CI=0.04, 0.93). Increased cannabis use over 6 months was associated with reduced odds of cigarette smoking abstinence among PWH who were motivated to quit. Additional factors that influence cannabis use and cigarette cessation simultaneously are in need of further study.


Aspects of modelling and simulating tumor growth and treatment.
The proliferation of malignant cells and tumor growth can be studied at various levels and from different viewpoints in the field of tumor biology and oncology. The aim of this paper is to outline how control theory and computer science can pave the way to new approaches to interpreting tumor growth and treatment. The present development is based on the hypothesis that the proliferation of malignant cells may be simulated by an unstable closed-loop control circuit. This type of model only describes the number of cells as a function of time. Therefore, an extended model permitting the study of the spatial structure of tumor growth is chosen. This approach leads to three-dimensional models simulating tumor growth in a vascularized tissue segment and opens the possibility of determining optimized chemotherapeutic tumor-treatment schedules. In the future it may become possible to perform computer simulations of different kinds of tumor treatment prior to clinical therapy.


Paradoxical emboli from left superior vena cava causing recurrent brain abscess.
Persistent left superior vena cava is a rare but well-recognised condition. We describe a case of persistent left superior vena cava draining directly into the left atrium, with a fixed anatomical right-to-left shunt and paradoxical embolic events causing recurrent brain abscess. Surgical ligation was curative.


A controlled study of cellular immune function in affective disorders before and during somatic therapy.
Lymphocyte blastogenesis induced by lectins (PHA, Con A, and PWM) was assessed in 27 drug-free patients with unipolar (n = 21) or bipolar (n = 5) depression and 13 normal controls. Fifteen patients were restudied after clinical remission. Symptomatic patients did not differ from controls nor did endogenous and nonendogenous depressions differ in their lymphocyte blastogenesis response to any of the three lectins. However, a significant reduction in lymphocyte blastogenesis with both PHA and Con A stimulation was found following somatic treatment. Cellular immune function appears to be normal in depressed patients, although the somatic therapies are associated with a reduction in this function.


Antigen-specific HLA-restricted human T-cell lines. I. An MT3-like restriction determinant distinct from HLA-DR.
The results presented provide evidence that the HLA specificity known as MT3, BR4, or Hon7 can serve as a restriction epitope for the proliferation of certain T cells responding to mumps viral antigen. This restriction determinant was found to be HLA-linked in family studies, and to segregate centromeric to a crossover between HLA-B and DR in one family. In the population studied, the specificity was found to be associated with the DR antigens DR4, DR7, and DRw9, which are known to be associated with MT3. The ability of accessory cells to present mumps antigen in the context of this supertypic restriction determinant was blocked by a monoclonal antibody specific for MT3. Since MT3 (BR4, Hon7) has been shown to be expressed on molecules distinct from DR, our experiments suggest that such molecules are functionally important in antigen presentation to T cells.


[Corneal endothelial cell changes in triple procedure].
A retrospective study was performed to examine time-related changes in the corneal endothelium in eyes that underwent a triple procedure consisting of penetrating keratoplasty, extracapsular excision, and intraocular lens (IOL) insertion. We studied 39 eyes from 36 patients who underwent a triple procedure associated with corneal transplantation at Tokyo Medical University between February 1989 and May 1996. The ages of the patients at the time of operation ranged from 61 to 91 years (mean, 70.9 +/- 10.8 years). The postoperative follow-up period ranged from 13.6 to 107.5 months (mean, 53.4 +/- 27.1 months). The following were evaluated: 1) cure rate of transparency, 2) complications, 3) time-related changes of endothelial cell density during 7 years after operation, and 4) comparison of changes in endothelial cell density associated with various factors such as primary disease, graft, IOL, and rejection. The following results were obtained. 1. The cure rate of transparency of the graft at the last examination(a mean of 53.4 +/- 27.1 months after surgery) was 82.1%. 2. The incidence of rejection at the last examination was 35.9%. 3. The mean endothelial cell density in the graft was 2945.8 cells/mm2 before operation, and decreased to 1806.7 cells/mm2 one year after operation, and further to 1161.1 cells/mm2 five years after operation, showing a reduction of 60.6% compared to the mean before operation. 4. The annual rate of endothelial cell reduction in the same patient was approximately 25% the first year after operation and gradually lessened from the second year, reaching a stable level of 6% after the third year. 5. The punching method(done from the epithelial side), diameter of optical zone of IOL (6 mm or less), and rejection contributed to the reduction of endothelial cell density by one year after the operation. The triple procedure is considered to be a technique that may be chosen actively.


Human cell-mediated immunity to tuberculin as assayed by the agarose micro-droplet leukocyte migration inhibition technique: comparison with the capillary tube assay.
Direct and indirect agarose microdroplet migration inhibition assays were performed with log dilutions (50--5 X 10(-8) microgram/ml) of soluble purified protein derivative (PPD) of tuberculin and leukocytes (4 X 10(5)/droplet) from PPD skin test positive or negative individuals. Some tests were run in parallel with the capillary tube method. Inhibition of migration of leukocytes from 9/11 PPD skin test positive donors studied was observed in direct tests when employing PPD doses ranging from 1--50 microgram/ml PPD. Inhibition of migration of leukocytes from some PPD skin reactive donors was obtained with as little as 5 X 10(-3)--5 X 10(-7) microgram/ml (i.e., 5 nanograms to 0.5 picograms). Some inhibition of leukocyte migration was seen with skin test negative donors (presumably toxicity) with the higher doses of PPD (50 microgram/ml), but generally little inhibition was observed with these donors at lower doses. Comparative experimetns of the agarose micromethod and the capillary tube technique indicated that the agarose assay was more sensitive in that it could detect reactivity with 2--4 logs lower antigen concentration. Indirect assays using supernatants of cultures of PPD triggered mononuclear cells and indicator granulocytes in agarose droplets demonstrating that a lymphokine (presumable leukocyte inhibitory factor) was being produced and suggested that cell-mediate immune (CMI) reactions were operative. The results indicate the usefulness of this technique in the sensitive-detection of CMI against such antigens as soluble PPD. The assay should prove useful in quantitative assessment of cell-mediated reactivity by using a wide range of antigen concentrations and the leukocytes from as little as 2--5 ml of blood.


Persistent organic pollutants and contaminants of emerging concern in spinner dolphins (Stenella longirostris) from the Western Atlantic Ocean.
The presence and distribution of persistent organic pollutants (POPs) and contaminants of emerging concern (CECs) were evaluated in spinner dolphins (Stenella longirostris) from the Fernando de Noronha Archipelago (Western Atlantic Ocean). Blubber samples (n = 37) were Soxhlet extracted and analyzed using gas chromatography tandem mass spectrometry. The levels of POPs reported in this study are far below those previously reported in spinner dolphins from the Indian and Pacific Oceans. Despite relatively low levels of contaminants, the presence of chemicals represents an additional stressor to these marine mammals, which are subject to increasing anthropogenic pressures, especially regarding tourism activities, in Fernando de Noronha.


In-situ spatial and temporal electrical characterization of ZnO thin films deposited by atmospheric pressure chemical vapour deposition on flexible polymer substrates.
A technique is presented for collecting data on both the spatial and temporal variations in the electrical properties of a film as it is deposited on a flexible substrate. A flexible printed circuit board substrate with parallel electrodes distributed across its surface was designed. Zinc oxide films were then deposited on the flexible substrate at different temperatures via atmospheric pressure chemical vapour deposition (AP-CVD) using a spatial atomic layer deposition system. AP-CVD is a promising high-throughput thin film deposition technique with applications in flexible electronics. Collecting data on the film properties in-situ allows us to directly observe how deposition conditions affect the evolution of those properties in real-time. The spatial uniformity of the growing film was monitored, and the various stages of film nucleation and growth on the polymer substrate were observed. The measured resistance of the films was observed to be very high until a critical amount of material has been deposited, consistent with Volmer-Weber growth. Furthermore, monitoring the film resistance during post-deposition cooling enabled immediate identification of metallic or semiconducting behaviour within the conductive ZnO films. This technique allows for a more complete understanding of metal chalcogen film growth and properties, and the high volume of data generated will be useful for future implementations of machine-learning directed materials science.


The Murky Life of Merkel Cell Polyomavirus.
Merkel cell polyomavirus (MCPyV) expressing viral T antigens is a common feature of most Merkel cell carcinomas, a primary neuroendocrine skin tumor. MCPyV has been difficult to propagate in vitro. In this issue of Cell Host & Microbe, Liu et al. (2016) report that human dermal fibroblasts support productive MCPyV infection.


Phase-locking in double-point-contact spin-transfer devices.
Spin-transfer in nanometre-scale magnetic devices results from the torque on a ferromagnet owing to its interaction with a spin-polarized current and the electrons' spin angular momentum. Experiments have detected either a reversal or high-frequency (GHz) steady-state precession of the magnetization in giant magnetoresistance spin valves and magnetic tunnel junctions with current densities of more than 10(7) A cm(-2). Spin-transfer devices may enable high-density, low-power magnetic random access memory or direct-current-driven nanometre-sized microwave oscillators. Here we show that the magnetization oscillations induced by spin-transfer in two 80-nm-diameter giant-magnetoresistance point contacts in close proximity to each other can phase-lock into a single resonance over a frequency range from approximately <10 to >24 GHz for contact spacings of less than about approximately 200 nm. The output power from these contact pairs with small spacing is approximately twice the total power from more widely spaced (approximately 400 nm and greater) contact pairs that undergo separate resonances, indicating that the closely spaced pairs are phase-locked with zero phase shift. Phase-locking may enable control of large arrays of coupled spin-transfer devices with increased power output for microwave oscillator applications.


Effects of Shenling Baizhu powder on intestinal microflora metabolites and liver mitochondrial energy metabolism in nonalcoholic fatty liver mice.
Non-alcoholic fatty liver disease (NAFLD) is characterised by the excessive accumulation of triglycerides in the liver. Shenling Baizhu powder (SLBZP) is formulated from various natural medicinal plants that protect the liver and are used to treat intestinal diseases. SLBZP improves the symptoms of NAFLD. However, its mechanism of action remains unclear. Herein, we investigated the ameliorative effect of SLBZP on model mice with high-fat-diet (HFD)-induced NAFLD. Additionally, we evaluated the impact of SLBZP on the intestinal flora and its metabolites and mitochondrial energy metabolism in NAFLD. We used HFD to establish a mouse model of NAFLD. Different drug interventions were administered. We measured serum biochemical indices. Liver sections were visualised with hematoxylin-eosin and oil red O staining. 16S rDNA amplicon sequencing technology was used to analyse the diversity and abundance of the intestinal flora. Short-chain fatty acids (SCFAs) in the intestinal contents were detected using GC-MS. Liver tissue was sampled to detect mitochondrial membrane functional indices. Western blotting was used to determine the levels of mitochondrial pathway-related proteins, namely, uncoupling protein 2 (UCP2), adenosine monophosphate-activated protein kinase (AMPK) and inhibitory factor 1 (IF1) of F1Fo ATP synthesis/hydrolase, in the liver. The spleen-invigorating classic recipe of SLBZP reduced liver lipid deposition in mice with HFD-induced NAFLD. Additionally, SCFAs produced by intestinal flora metabolism regulated the UCP2/AMPK/IF1 signalling pathway involved in liver mitochondrial energy metabolism to improve the liver mitochondrial membrane permeability, respiratory state and oxidative phosphorylation efficiency of mice with NAFLD. Finally, SLBZP increased the liver ATP level. Our results suggest that the therapeutic effect of SLBZP on NAFLD is related to the regulation of hepatic mitochondrial energy metabolism by intestinal flora and its metabolites and is possibly associated with the UCP2/AMPK/IF1 signalling pathway.


Editorial: fecal granins in IBS: cause or indicator of intestinal or colonic irritation?
Ohman et al. report increased fecal granins in patients with irritable bowel syndrome (IBS). Several interesting questions arise from their observations. Are the granins a cause of the pathophysiology or phenotype in IBS? Is the elevation of granins specific to IBS? What is the cause of increased fecal granin levels? Can fecal granin levels be used to diagnose IBS? Are increased fecal granins an expression of intestinal or colonic irritation? This paper adds to the body of evidence suggesting there are gastrointestinal disturbances in IBS; understanding these disturbances may provide clues to its pathogenesis and optimize management.


Penetrating colon trauma - outcomes related to single versus multiple colonic injuries.
There is no conclusive evidence to guide surgical management in the presence of multiple colonic injuries as opposed to a single colonic injury, and whether multiple colonic suture lines are associated with worse outcomes than single suture lines. We reviewed the outcomes of penetrating colonic trauma in relation to whether patients had single versus multiple colonic suture lines (primary repair or anastomosis) following laparotomy. A retrospective study was conducted at a major trauma centre in South Africa from 2012-2020 for all patients over 18 years who had sustained penetrating colon injury. 541 cases were included: 409 with single suture line and 54 with multiple suture lines. There were no differences between groups in terms of mechanism of injury (gunshot vs stab; p = 0.328), Injury Severity Score (p = 0.071), or Penetrating Abdominal Trauma Index (p = 0.396). Admission lactate was worse for multiple suture line patients (p = 0.049), but no other blood gas parameters were different, and there was no higher incidence of damage control surgery (p = 0.558) or ICU admission (p = 0.156) for this group. There was a higher rate of diversion in the multiple suture line group (p < 0.001). Univariable logistic regression did not show an increased risk of gastro-intestinal complications, suture line leak rate, or mortality for multiple suture lines compared to single. It appears that there is no appreciable difference in outcome between patients with a single colonic suture line compared to patients with more than one suture line following trauma laparotomy. In light of this, each injury should be treated on its own merit, in the context of the patient's overall physiological condition, without undue fear of leaving the patient with more than one colonic suture line. However, judicious use of diversion remains advisable.


Monitoring at home.
To reduce time committment and expense in the diagnosis of sleep apnea it is necessary to develop simplified monitoring techniques. The monitoring systems to detect apneas should have high sensitivity, good reproducibility, be inexpensive and practical to use. The following methods have been suggested: inductance plethysmography, capnography, flow measurements by thermistors, tracheal sound recording, static charge sensitivity bed, oximetry, activity monitoring, detection of snoring. Some devices to registrate breathing have been combined with oximetry and other methods. The results have been validated by polysomnography and show rather good correlations. However, there exists no information on the time and cost savings of a step wise diagnosis of sleep apnea.


Characterization of 69- and 100-kDa forms of 2-5A-synthetase from interferon-treated human cells.
The existence of distinct 69- and 100-kDa forms of 2-5A-synthetase in addition to the smaller (40 and 46 kDa) forms has recently been established. Using specific monoclonal antibodies we investigated the induction, synthesis, and activity of 69- and 100-kDa 2',5'-oligoadenylate (2-5A) synthetases in interferon-treated human Daudi cells. Although induction of these synthetases is detectable in cells treated with as little as 1-5 units/ml of human alpha-interferon, higher concentrations are required for maximum synthesis of the 100 kDa than the 69-kDa protein. At 5 units/ml of interferon, enhanced synthesis of both proteins is detectable at 4 h with maximum synthesis occurring between 8 to 12 and 12 to 16 h for 69- and 100-kDa 2-5A-synthetases, respectively. At 24 h after addition of interferon, synthesis of these synthetases declines due to a decrease of active interferon in the culture medium. The synthesis of both synthetases is blocked by actinomycin D, and the half-life of these proteins is estimated to be 8 h. The activities of immunoaffinity purified 69- and 100-kDa synthetases are dependent on double-stranded (ds)RNA but show different requirements for optimum concentration of dsRNA and pH of the reaction. The apparent Km of 69- and 100-kDa synthetases for ATP is 1.7 X 10(-3) M and 3.6 X 10(-3) M, respectively. At optimum conditions for the activity of these enzymes, the pattern of 2',5'-linked oligoadenylates synthesized are different, the 69-kDa protein synthesizing higher oligomers than the 100-kDa species. Taken together, these results indicate that the 69- and 100-kDa 2-5A-synthetases are distinct proteins each with specific characteristics of induction and enzymatic activity.


Application of amplitude-modulated radiofrequency fields to the magic-angle spinning NMR of spin-7/2 nuclei.
We report pulse sequences for the sensitivity enhancement of magic-angle spinning and multiple-quantum magic-angle spinning spectra of spin-72 systems. Sensitivity enhancement is obtained with the use of fast amplitude-modulated (FAM) radiofrequency pulses. In one-dimensional magic-angle spinning experiments, signal enhancement of 3 is obtained by a FAM pulse followed by a soft 90 degrees pulse. In two-dimensional multiple-quantum magic-angle spinning experiments, FAM pulses are used for both the excitation of multiple-quantum coherences and for their conversion into observable single-quantum coherences. The observed signal enhancements are 2.2 in 3Q experiments, 3.1 in 5Q experiments, and 4.1 in 7Q experiments, compared to the conventional two-pulse scheme. The pulse schemes are demonstrated on the 45Sc NMR of Sc2(SO4)3 x 5H2O and the 139La NMR of LaAlO3. We also demonstrate the generation of FAM pulses by double-frequency irradiation.


Mycobacterium malmoense infection. An unusual cause of wrist swelling.
We report a case of non-tuberculous tenosynovitis of the wrist caused by Mycobacterium malmoense. The patient presented with a ganglion-like swelling on the flexor aspect of the wrist. The diagnosis was confirmed by fine needle aspiration biopsy. A satisfactory resolution was obtained by antibiotic therapy alone, indicating that radical synovectomy may not be necessary in all cases of M. malmoense infection.