Circulating tumor necrosis factor-alpha correlates with electrodiagnostic abnormalities in Guillain-Barré syndrome.
Autoimmune damage to peripheral nerves, mediated by activated T lymphocytes and macrophages, underlies the pathogenesis of inflammatory demyelination in Guillain-Barré syndrome. Both T lymphocytes and macrophages secrete tumor necrosis factor-alpha, a cytokine that exerts toxic effects on myelin, Schwann cells, and endothelial cells. The reportedly high serum levels of this cytokine in patients with Guillain-Barré syndrome may reflect the degree of immune activation rather than a direct pathogenic effect. We compared serum levels of tumor necrosis factor-alpha, interleukin-1 beta, and soluble interleukin-2 receptor with well-established electrodiagnostic criteria for primary demyelination in 23 patients with Guillain-Barré syndrome, to assess the relationship between these cytokines and peripheral myelin damage. High serum levels of tumor necrosis factor-alpha were associated with prolonged distal motor latencies and slowed motor conduction velocities, prolonged or absent F-wave responses, and reduced amplitude of distal compound muscle action potentials. No significant correlation was observed between electrodiagnostic criteria for primary demyelination and serum levels of interleukin-1 beta or soluble interleukin-2 receptor. These findings suggest a putative role of tumor necrosis factor-alpha in the pathogenesis of peripheral nerve demyelination in Guillain-Barré syndrome.


Development of a Dynamic Oriented Rehabilitative Integrated System (DORIS) and Preliminary Tests.
Moving platforms were introduced in the field of the study of posturography since the 1970s. Commercial platforms have some limits: a limited number of degrees of freedom, pre-configured protocols, and, usually, they are expensive. In order to overcome these limits, we developed a robotic platform: Dynamic Oriented Rehabilitative Integrated System (DORIS). We aimed at realizing a versatile solution that can be applied both for research purposes but also for personalizing the training of equilibrium and gait. We reached these goals by means of a Stewart platform that was realized with linear actuators and a supporting plate. Each actuator is provided by an ad hoc built monoaxial load cell. Position control allows a large range of movements and load cells measure the reactive force applied by the subject. Transmission Control Protocol/Internet Protocol (TCP/IP) guarantees the communication between the platform and other systems. We integrated DORIS with a motion analysis system, an electromyography (EMG) system, and a virtual reality environment (VR). This integration and the custom design of the platform offer the opportunity to manipulate the available information of the subject under analysis, which uses visual, vestibular, and plantar feet pressure inputs. The full access to the human movements and to the dynamic interaction is a further benefit for the identification of innovative solutions for research and physical rehabilitation purposes in a field that is widely investigated but still open.


Bubble Cloud Behavior and Ablation Capacity for Histotripsy Generated from Intrinsic or Artificial Cavitation Nuclei.
The study described here examined the effects of cavitation nuclei characteristics on histotripsy. High-speed optical imaging was used to compare bubble cloud behavior and ablation capacity for histotripsy generated from intrinsic and artificial cavitation nuclei (gas-filled microbubbles, fluid-filled nanocones). Results showed a significant decrease in the cavitation threshold for microbubbles and nanocones compared with intrinsic-nuclei controls, with predictable and well-defined bubble clouds generated in all cases. Red blood cell experiments showed complete ablations for intrinsic and nanocone phantoms, but only partial ablation in microbubble phantoms. Results also revealed a lower rate of ablation in artificial-nuclei phantoms because of reduced bubble expansion (and corresponding decreases in stress and strain). Overall, this study demonstrates the potential of using artificial nuclei to reduce the histotripsy cavitation threshold while highlighting differences in the bubble cloud behavior and ablation capacity that need to be considered in the future development of these approaches.


Differences in airway wall compliance as a possible mechanism for wheezing disorders in infants.
High-frequency input impedance measurements (Z(f)) provide useful noninvasive information on airway geometry and especially airway wall mechanics in the canine and human adult respiratory system. Using the high-speed interrupter technique (HIT), we have shown that it is possible to measure high-frequency Z(f) in infants up to 900 Hz, including antiresonant phenomena which are known to be related to wave propagation velocity. This implies that the first antiresonant frequency (far,1) is a function of airway wall compliance. Since, airway wall mechanics are particularly important for the flow limitation phenomena, we wondered whether we could find evidence that airway wall properties were important for the occurrence of flow limitation during incremental methacholine challenge in infants. We measured Z(f) from 32-900 Hz and maximal flow at functional residual capacity (V'maxFRC) by the rapid chest compression technique in 10 infants (aged 36-81 weeks) with wheezing disorders. far,1 increased significantly at very low doses of mch before any decline could be detected in V'maxFRC. We hypothesize that these changes in far,1 are determined by mch-induced decrease in airway wall compliance. High-speed interrupter technique in combination with rapid chest compression technique can be used to study developmental differences in airway function (particularly of airway wall properties) and their contribution to airway disease and response to bronchodilator therapy in infants.


Preventing perinatal depression in low-income home visiting clients: a randomized controlled trial.
To assess the efficacy of a 6-week cognitive-behavioral intervention in preventing the onset of perinatal depression and reducing depressive symptoms among low-income women in home visitation programs. Sixty-one women who were pregnant or who had a child less than 6 months of age and who were assessed as at risk for perinatal depression were randomized to a 6-week, group-based cognitive-behavioral intervention or usual home visiting services. Study participants were predominately African American, unmarried, and unemployed. Intervention sessions were led by a licensed clinical social worker or clinical psychologist. Home visitors provided 1-on-1 reinforcement of key intervention messages between group sessions. Depressive symptoms were measured with the Beck Depression Inventory-II (Beck, Steer, & Brown, 1996), and major depressive episodes were measured with the Maternal Mood Screener (MMS; Le & Muñoz, 1998). Outcomes were assessed at baseline and at 1 week and 3 months postintervention. Repeated measures analysis of variance indicated that there was a significant Time × Condition interaction, F(2, 112) = 4.1, p = .02. At 3 months postintervention, 9 of 27 (33%) women receiving usual care reported levels of depressive symptoms that met clinical cutoff for depression on the MMS compared with 3 of 32 (9%) women in the intervention condition, χ²(1, N = 59) = 5.18, p < .05. This study provides preliminary data on the efficacy of a cognitive-behavioral intervention to prevent perinatal depression among home visiting clients and suggests it is feasible to embed such an intervention in home visitation programs. A larger trial is warranted to attempt to replicate study findings.


Kinematic 3-D motion analysis of shoulder resurfacing hemiarthroplasty - An objective assessment method.
Shoulder replacement is indicated in the treatment of pain due to osteoarthritis. Few studies have objectively assessed range of motion (RoM) gains at different post-operative time points. This is a prospective 3D motion analysis study to objectively quantify RoM changes at multiple time points following shoulder resurfacing arthroplasty (SRA) for primary gleno-humeral osteoarthritis, comparing it with clinically measured RoM. Clinical assessment, Visual Analog Scale (VAS) pain score, Constant-Morley (CS) and Oxford Shoulder Score (OSS) were recorded. Motion analysis was performed for RoM and three activities of daily living tasks (ADL), pre-operatively and post-operatively at 4 and 12 months. Nineteen shoulders in fifteen patients were included. The mean age was 72 years (range 52-84). There were significant improvements in external and internal rotation, ability to place the hand behind the head and reach the fifth lumbar vertebra, at 4 months on clinical examination and kinematic analysis with no further improvements at 12 months. There was significant improvement in abduction at 4 months with further improvement at 12 months, which was significantly more than noted on clinical assessment. In contrast, kinematic analysis showed a reduction in flexion between 4 and 12 months, while clinically there appeared to be an improvement between these time periods. This is the first study to prospectively utilise objective kinematic 3-D motion analysis in addition to clinical measurements and outcome scores, to investigate the outcome of resurfacing arthroplasty at multiple time points after surgery, providing an understanding into the trends of change in these parameters.


The effect of group support psychotherapy on adherence to anti-retroviral therapy and viral suppression among HIV positive young people: Study protocol for a pilot randomized controlled trial.
Several studies have demonstrated an association between psychological risk factors and HIV disease progression. However, there is limited information on the use of psychological interventions to improve HIV treatment outcomes in young people living with HIV. This pilot trial aims to evaluate the feasibility, acceptability and preliminary effectiveness of group support psychotherapy in improving adherence to anti-retroviral therapy and viral suppression in young people living with HIV in Uganda. We recruited 120 young people with HIV, aged 10-18 years, who had non-viral suppression 6 months after initiating first-line anti-retroviral therapy (ART) from community based HIV clinics in Kitgum district, northern Uganda. Participants were randomly assigned to receive GSP plus IAC (N = 60) or IAC alone (N = 60). Primary outcomes will be indicators of feasibility and acceptability as well as preliminary effectiveness of GSP in improving ART adherence and viral suppression analysed by intention to treat using cluster-adjusted t tests and permutation tests. Secondary outcomes will be measures of depression, anxiety and cost-effectiveness. The trial has been approved by the Makerere College of Health Sciences School of Health Sciences Research Ethics Committee, and the Uganda National Council of Science and Technology. Recruitment began in June 2021 and 120 young people living with HIV with their adult caregivers have been recruited to the trial. An analysis of baseline and 6-month data is in progress. The results of this trial will not only be presented at national and international conferences but also submitted for publication in peer-reviewed journals and as a report to the funding agencies. This pilot trial will provide critical evidence to support the ongoing mental health integration into routine HIV care in Uganda. Pan African Clinical Trials Registry (PACTR): 202006601935462.


Lung cancer symptom appraisal among people with chronic obstructive pulmonary disease: A qualitative interview study.
The incidence of lung cancer is four times higher in people with chronic obstructive pulmonary disease (COPD) compared with the general population. Promotion of a shorter time from symptom onset to presentation is one potential strategy for earlier lung cancer diagnosis, but distinguishing respiratory symptoms can be difficult. We investigated how the experience of COPD influences symptom appraisal and help seeking for potential lung cancer symptoms. We conducted qualitative interviews with men (n = 17) and women (n = 23) aged 40 to 83 years with COPD. Topic guides drew on the integrated symptom-response framework and covered symptom experience, interpretation, action, recognition, help seeking, evaluation, and reevaluation. We used the framework method to analyse the data. Participants said that they attributed chest symptoms to their COPD; no other cause was considered. Participants said that family/friends noticed changes in their symptoms and encouraged help seeking. Others felt isolated by their COPD because they could not get out, were fatigued, or were embarrassed. Participants visited health professionals frequently, but increased risk of lung cancer was not discussed. Our study provides insight into different levels of influence on symptom appraisal and targets for intervention. Greater awareness of increased lung cancer risk and support to act on symptom changes is essential and could be achieved through a concerted information campaign. Health professionals working with people with COPD could also optimise appointments to support symptom appraisal of potential lung cancer symptoms.


Estimating Downstream Budget Impacts in Implementation Research.
Health care decision makers often request information showing how a new treatment or intervention will affect their budget (i.e., a budget impact analysis; BIA). In this article, we present key topics for considering how to measure downstream health care costs, a key component of the BIA, when implementing an evidence-based program designed to reduce a quality gap. Tracking health care utilization can be done with administrative or self-reported data, but estimating costs for these utilization data raises 2 issues that are often overlooked in implementation science. The first issue has to do with applicability: are the cost estimates applicable to the health care system that is implementing the quality improvement program? We often use national cost estimates or average payments, without considering whether these cost estimates are appropriate. Second, we need to determine the decision maker's time horizon to identify the costs that vary in that time horizon. If the BIA takes a short-term time horizon, then we should focus on costs that vary in the short run and exclude costs that are fixed over this time. BIA is an increasingly popular tool for health care decision makers interested in understanding the financial effect of implementing an evidence-based program. Without careful consideration of some key conceptual issues, we run the risk of misleading decision makers when presenting results from implementation studies.


Partial-volume effect correction in positron emission tomography brain scan image using super-resolution image reconstruction.
The partial-volume effect (PVE) is a consequence of limited (i.e. finite) spatial resolution. PVE can lead to quantitative underestimation of activity concentrations in reconstructed images, which may result in misinterpretation of positron emission tomography (PET) scan images, especially in the brain. The PVE becomes significant when the dimensions of a source region are less than two to three times the full width at half maximum spatial resolution of the imaging system. In the present study, the ability of super-resolution (SR) image reconstruction to compensate for PVE in PET was characterized. The ability of SR image reconstruction technique to recover activity concentrations in small structures was evaluated by comparing images before and after image reconstruction in the NEMA/IEC phantom (Washington, DC), in the Hoffman brain phantom and in four human brain subjects (three normal subjects and one atrophic brain subject) in terms of apparent recovery coefficient (ARC) and percentage yield. Both the ARC and percentage yield are improved after SR implementation in NEMA/IEC phantom and Hoffman brain phantom. When tested in normal subjects, SR implementation can improve the intensity and justify SR efficiency to correct PVE. SR algorithm can be used to effectively correct PVE in PET images. The current research focused on brain PET scanning exclusively; future work will extend to whole-body imaging.


Fondazione Italiana Linfomi (FIL) expert consensus on the use of intensity-modulated and image-guided radiotherapy for Hodgkin's lymphoma involving the mediastinum.
Advances in therapy have resulted in improved cure rates and an increasing number of long-term Hodgkin's lymphoma (HL) survivors. However, radiotherapy (RT)-related late effects are still a significant issue, particularly for younger patients with mediastinal disease (secondary cancers, heart diseases). In many Centers, technological evolution has substantially changed RT planning and delivery. This consensus document aims to analyze the current knowledge of Intensity-Modulated Radiation Therapy (IMRT) and Image-Guided Radiation Therapy (IGRT) for mediastinal HL and formulate practical recommendations based on scientific evidence and expert opinions. A dedicated working group was set up within the Fondazione Italiana Linfomi (FIL) Radiotherapy Committee in May 2018. After a first meeting, the group adopted a dedicated platform to share retrieved articles and other material. Two group coordinators redacted a first document draft, that was further discussed and finalized in two subsequent meetings. Topics of interest were: 1) Published data comparing 3D-conformal radiotherapy (3D-CRT) and IMRT 2) dose objectives for the organs at risk 3) IGRT protocols and motion management. Data review showed that IMRT might allow for an essential reduction in the high-dose regions for all different thoracic OAR. As very few studies included specific dose constraints for lungs and breasts, the low-dose component for these OAR resulted slightly higher with IMRT vs. 3D-CRT, depending on the technique used. We propose a set of dose objectives for the heart, breasts, lungs, and thyroid. The use of IGRT is advised for margin reduction without specific indications, such as the use of breath-holding techniques. An individual approach, including comparative planning and considering different risk factors for late morbidity, is recommended for each patient. As HL therapy continues to evolve, with an emphasis on treatment reduction, radiation oncologists should use at best all the available tools to minimize the dose to organs at risk and optimize treatment plans. This document provides indications on the use of IMRT/IGRT based on expert consensus, providing a basis for clinical implementation and future development.


Diabetic neuropathy after pancreas transplantation: determinants of recovery.
Although simultaneous pancreas and kidney transplantation (SPK) achieves normoglycemia and correction of uremia in type I diabetic patients with renal failure, little data are available on long-term outcome and clinical determinants of recovery of peripheral neuropathy. In this prospective study, 219 electrophysiological studies using a standardized protocol were performed before and up to 8 years after SPK in 44 patients. Nine control diabetic recipients with functioning kidney but nonfunctioning pancreas transplants were studied on 35 occasions. Patients were 38.5+/-7.9 years old (mean+/-SD) with pretransplant diabetes present for 25.2+/-7.6 years. Significant polyneuropathy (total nerve conduction scores [NCS] <-1.0) was present in 89% before transplantation, which correlated with body weight (r=0.628, P<0.001). Two distinct patterns of neurological recovery were observed after SPK. Conduction velocity (CV) improved in a biphasic pattern, with a rapid initial recovery followed by subsequent stabilization. In contrast, the recovery of nerve amplitude was monophasic, and continued to improve for up to 8 years. Initial improvement in NCS was primarily due to an increase in CV (P=0.002 vs. baseline), and was best in shorter and younger patients. Recovery of total NCS at 6 months after SPK, assessed by multivariate analysis, was least in obese recipients and when performed in patients who had started dialysis before SPK, and was associated with lower transplant kidney isotopic glomerular filtration rate and HLA mismatch (P<0.05 to 0.001). Subsequent improvement was associated with less severe initial neuropathy, smaller body weight, and longer duration of diabetes (P<0.01 to 0.001). Fasting hyperinsulinemia was associated with impairment of initial recovery and subsequent NCS after SPK, but was worse in the control group. Recovery of nerve action potential amplitudes was predicted by better initial amplitudes and HLA mismatch, lower body weight, and the use of nifedipine (P<0.05 to 0.001). Nifedipine was used for hypertension in 33% of SPK and was associated with better CV and amplitudes, particularly in the upper limbs, where there was less neuropathy. The use of angiotensin-converting enzyme inhibitors also appeared beneficial, but this was confined to the lower limbs. SPK resulted in a gradual, sustained, and late improvement in nerve action potential amplitudes, consistent with axonal regeneration and partial reversal of diabetic neuropathy. These data suggest that early transplantation of uremic diabetic patients before onset of severe neuropathy, minimizing obesity and optimizing renal transplant function, maximizes neurological recovery after SPK. Furthermore, the preliminary data support randomized clinical trials for evaluation of nifedipine and angiotensin-converting enzyme inhibitors in diabetic neuropathy.


[Liver regeneration after resection: molecular and cellular mechanism].
It has been well established that the liver can regenerate after resection. Liver regeneration is a fundamental mechanism by which the liver responds to injury. This review article discusses molecular and cellular mechanism of liver regeneration, including growth factors and cytokines in the initiation and regulation of liver regeneration, the importance of the liver extracellular matrix and its dynamic effect on hepatocyte growth, and finally, stem cell biology in liver regeneration.


Support to aging parents and grown children in Black and White families.
Black and White middle-aged adults typically are in a pivot position of providing support to generations above and below. Racial differences in support to each generation in the family remain unclear, however. Different factors may account for racial differences in support of grown children versus aging parents. Middle-aged adults (aged 40-60 years; 35%, n = 216 Black and 65%, n = 397 White) rated social support they provided each aging parent and grown child. Participants reported background characteristics representing their resources and measures of needs for each family member. Interviews also assessed beliefs about obligation to support parents and grown children and rewards from helping. Multilevel models revealed White middle-aged adults provided more support to grown children than Black middle-aged adults. Demands from offspring, beliefs about support, and rewards from helping explained these racial differences. Black middle-aged adults provided more support to parents than White middle-aged adults. Beliefs about support and feelings of personal reward from providing support explained this difference but resources and demands did not. Racial differences varied by generation (parent or offspring). The prolonged transitions common for White young adults explained racial differences in support of offspring. Middle-aged adults may treat support of parents as more discretionary, with cultural ideas about obligation and personal rewards guiding behaviors.


Non-professional Medical Interpreting as a Contextualized Practice: Chinese Volunteer Interpreters' Role-Spaces in Mediating Provider-Patient Conflicts Amid the Pandemic.
Non-professional medical interpreters are frequent participants of bilingual health communication. Yet, scholarly attention paid to this group's roles in less routinized medical encounters is insufficient. Adopting the concept of "role-space," this study explores volunteer medical interpreters' (VMIs) roles in mediating provider-patient conflicts at a designated hospital tasked to admit and treat foreign patients in City Y, China. In-depth interviews with eight VMIs, two doctors, two patients, and one Foreign Affairs officer indicate that VMIs took on the roles of provider proxy, patient advocates, information gatekeepers, and emotional supporters while navigating through challenges at the macro-, meso- and micro-level; Their practices led to four role-spaces that featured high presentation of VMIs' self-driven actions during dyadic communication with patients only and, in most cases, minimal interaction management and participant alignment in provider-patient encounters.


Toddler milk: a scoping review of research on consumption, perceptions, and marketing practices.
Toddler milk is an ultra-processed beverage consisting primarily of powdered milk, caloric sweeteners, and vegetable oil. Pediatric health authorities do not support the use of toddler milk, and emerging evidence suggests that toddler-milk marketing practices may mislead consumers. However, studies have not synthesized the extent of toddler-milk marketing practices or how these practices affect parents' decisions about whether to serve toddler milk. We aimed to summarize the literature about toddler milk to identify what is known about: (1) parents' toddler-milk purchasing and feeding behaviors, (2) toddler-milk marketing, and (3) how marketing practices influence parents' beliefs and perceptions about toddler milk. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), we systematically searched 8 databases (PubMed, APA PsycINFO, Scopus, Cochrane Central, Embase, CINAHL, Communication & Mass Media Complete, and Business Source Premier). We identified 45 articles about toddler milk. Studies were conducted in 25 countries across 6 continents. Five types of findings emerged: (1) consumption and feeding behaviors, (2) demographic correlates of toddler-milk purchasing and consumption, (3) misperceptions and beliefs, (4) increased sales, and (5) increased marketing and responses to marketing. The included articles suggested that toddler-milk sales are growing rapidly worldwide. Findings also revealed that toddler-milk packages (eg, labels, branding) resemble infant formula packages and that toddler-milk marketing practices may indirectly advertise infant formula. Purchasing, serving, and consumption of toddler milk were higher in Black and Hispanic populations than in non-Hispanic White populations, and parents with higher educational attainment and income were more likely to offer toddler milk to their children. Findings suggest a need for policies to prevent cross-marketing of toddler milk and infant formula, reduce provision of toddler milk to infants and toddlers, and prevent caregivers from being misled about toddler-milk healthfulness.


Prognosis and management of scleroderma and scleroderma-like disorders in children.
Scleroderma is a spectrum of disorders of which juvenile scleroderma forms a part. Fortunately, most children develop one of the localised forms and systemic disease is late. The prognosis of any individual type of scleroderma is dependent upon the subset of the disease, its extent, and internal organ involvement. In childhood, the problem is usually not one of survival, but of morbidity due to atrophy of skin, muscle and bone, with the potential for eventual growth defects and deformity. Drug treatment, when required, is usually directed towards suppressing inflammation and collagen deposition; vascular therapy does not play a major role, but physical therapy is crucial in certain forms of the disease.


Evidence for multiple tachykinin receptor subtypes on the rabbit iris sphincter muscle.
The actions of mammalian tachykinins (substance P, substance K/neurokinin a, neuromedin K/neurokinin b) and non-mammalian tachykinins (eledoisin, kassinin, physalaemin) were compared on the rabbit pupillary sphincter. All acted as direct spasmogens with potencies in the order: eledoisin greater than physalaemin = neurokinin b = substance P greater than kassinin greater than neurokinin a. However, their actions could be divided into at least two categories on the basis of similar kinetics of contractions, differential sensitivity to the tachykinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11) substance P and specific cross-protection against phenoxybenzamine inactivation by structurally related tachykinins. The relationship between these observations and the suggested "P" and "E" subtypes of tachykinin receptors is discussed.


Idiopathic ventricular arrhythmias originating from the left ventricular summit: anatomic concepts relevant to ablation.
The summit of the left ventricle (LV) is the most superior portion of the epicardial LV bounded by an arc from the left anterior descending coronary artery, superior to the first septal perforating branch to the left circumflex coronary artery. Ventricular arrhythmias (VAs) originating from this region may present challenges for catheter ablation. We studied 27 consecutive patients with VAs originating from the LV summit. The great cardiac vein (GCV) divides this region between an inferior area accessible to ablation and a superior, inaccessible area. Successful ablation was achieved within the GCV in 14 patients and on the epicardial surface in 4. Ventricular prepotentials were recorded at the successful ablation site in 80% of these patients. In 5 patients, ablation was abandoned because of inaccessibility of the catheter to the myocardium or high impedance with radiofrequency application within the GCV. In the remaining 4 patients, epicardial mapping suggested VA origins in a region of low voltage that was located superior to the GCV (inaccessible area), and ablation was abandoned because of close proximity to the coronary arteries or high impedance. A right bundle-branch block, transition zone, R-wave amplitude ratio in leads III to II, Q-wave amplitude ratio in leads aVL to aVR, and S waves in lead V(6) accurately predicted the site of origin. LV summit VAs may be ablated within the GCV or inferior to the GCV on the epicardial surface, though sites superior to the GCV are usually inaccessible to ablation.


Emotional Exhaustion of Burnout Among Medical Staff and Its Association With Mindfulness and Social Support: A Single Center Study During the COVID-19 Pandemic in Japan.
Although higher rates of burnout have been reported during the COVID-19 pandemic, the contribution of the modifiable factors is lesser-known. We investigated how the risk of emotional exhaustion was associated with mindfulness skills and social support in a single medical center in Japan. We conducted a cross-sectional web survey on mental health for all staff of a national medical hospital from February to March 2021. We examined the association between self-rated emotional exhaustion and levels of mindfulness and social support using multivariate logistic regression. Of the 830 participants, signs of emotional exhaustion were observed in 261 (31%) individuals. Among those highly exposed to the virus at work, individuals with low levels of mindfulness and social support had significantly higher odds of emotional exhaustion [OR 3.46 (95% CI; 1.48-8.09), OR; 3.08 (95% CI; 1.33-7.13), respectively] compared to those with high levels. However, among those not highly exposed to the virus, individuals with both low and moderate levels of mindfulness had significantly higher odds of emotional exhaustion. [OR 3.33 (95% CI; 2.22-5.00), OR; 2.61 (95% CI; 1.73-3.94), respectively]. We found that factors associated with emotional exhaustion differed by exposure to SARS-CoV-2. Building mindfulness skills can help reduce the high burden placed on the staff. Additionally, increasing social support may be useful especially for workers highly exposed to SARS-CoV-2.


Embryonic extracts derived from the nematode Caenorhabditis elegans remove uracil from DNA by the sequential action of uracil-DNA glycosylase and AP (apurinic/apyrimidinic) endonuclease.
DNA bases continuously undergo modifications in response to endogenous reactions such as oxidation, alkylation or deamination. The modified bases are primarily removed by DNA glycosylases, which cleave the N-glycosylic bond linking the base to the sugar, to generate an apurinic/apyrimidinic (AP) site, and this latter lesion is highly mutagenic. Previously, no study has demonstrated the processing of these lesions in the nematode Caenorhabditis elegans. Herein, we report the existence of uracil-DNA glycosylase and AP endonuclease activities in extracts derived from embryos of C. elegans. These enzyme activities were monitored using a defined 5'-end (32)P-labelled 42-bp synthetic oligonucleotide substrate bearing a single uracil residue opposite guanine at position 21. The embryonic extract rapidly cleaved the substrate in a time-dependent manner to produce a 20-mer product. The extract did not excise adenine or thymine opposite guanine, although uracil opposite either adenine or thymine was processed. Addition of the highly specific inhibitor of uracil-DNA glycosylase produced by Bacillus subtilis to the extract prevented the formation of the 20-mer product, indicating that removal of uracil is catalysed by uracil-DNA glycosylase. The data suggest that the 20-mer product was generated by a sequential reaction, i.e., removal of the uracil base followed by 5'-cleavage of the AP site. Further analysis revealed that product formation was dependent upon the presence of Mg(2+), suggesting that cleavage of the AP site, following uracil excision, is carried out by a Mg(2+)-dependent AP endonuclease. It would appear that these activities correspond to the first two steps of a putative base-excision-repair pathway in C. elegans.


Tanshinone IIA improves diabetes mellitus via the NF-κB-induced AMPK signal pathway.
Diabetes mellitus (DM) is a systemic metabolic disease. Tanshinone IIA (Tan-IIA) presents potential benefits for DM. The purpose of this study was to investigate the efficacy of Tan-IIA in type 2 DM rats and explore its potential mechanism in renal cells. A type 2 DM rat model was established and administered with Tan-IIA or PBS. It was demonstrated that Tan-IIA treatment significantly reduced levels of total cholesterol, non-esterified fatty acids, total triglyceride and low-density lipoprotein cholesterol in experimental DM rats compared with the control group. The results indicated that Tan-IIA treatment significantly decreased levels of interleukin (IL)-8, tumor necrosis factor-α, C-reactive protein and IL-6. It was identified that Tan-IIA treatment significantly decreased nuclear factor-κB levels and significantly elevated 5' adenosine monophosphate-activated protein kinase levels. Western blot analysis indicated that Tan-IIA elevated immunocyte precipitation in renal cells. Furthermore, Tan-IIA treatment improved lipid metabolism, glucose metabolism, insulin resistance and body weight of type 2 DM rats. In conclusion, Tan-IIA administration may inhibit inflammatory cytokines and alleviate type 2 DM symptoms in experimental rats.


Age-related disparities in cancer screening: analysis of 2001 Behavioral Risk Factor Surveillance System data.
Although few studies have explored age-related health care disparities, some researchers have asserted such disparities uniformly disfavor the elderly and are largely attributable to ageism in the health care system. We compared age-related patterns of screening for colorectal cancer with those for breast and prostate cancer in persons aged 50 years and older. We analyzed data for all adults aged 50 years and older (N = 88,213) in the 2001 Behavioral Risk Factor Surveillance System (BRFSS), a nationally representative, telephone-administered survey of personal health behaviors. Main outcome measures were adjusted prevalence by 5-year age-groups of colorectal cancer screening using fecal occult blood testing, flexible sigmoidoscopy, or colonoscopy for men and women; rates of mammography screening for women; and rates of prostate-specific antigen (PSA) screening for men. After adjustment for race/ethnicity, education level, income, health insurance, and self-rated health, predicted reported colorectal cancer screening (all modalities) increased significantly from when patients reached age 50 years until 70 to 74 years (66.0%, standard error [SE] 0.8%), remained constant until age 80 years, and then declined. The age-related gain in colorectal cancer screening was confined to whites among patients older than 60 years. Reported PSA screening increased until age 75 to 79 years (79.3%, SE 1.1%) and then declined, whereas reported mammography screening peaked at age 55 to 59 years (83.3%, SE 1.2%) and then declined. Significant age-related disparities appear to exist for both evidence-based and non-evidence-based cancer-screening interventions. The issue of age-related disparities in cancer screening is complex, with the direction of disparity favoring the elderly for some services yet disfavoring them for others.


IVIG inhibits TNF-α-induced MMP9 expression and activity in monocytes by suppressing NF-κB and P38 MAPK activation.
Matrix metalloproteinase-9 (MMP9) has been involved in inflammatory and pathologic processes of coronary artery lesions (CAL) in Kawasaki disease (KD). Intravenous immunoglobulin (IVIG), a traditional treatment for Kawasaki disease, could decrease the expressions of MMP9. The purpose of this study was to investigate the protective effect of IVIG in chemotactic migration of monocyte and the regulation of MMP9 induced by tumor necrosis factor-α (TNF-α) in U937s. Studies were carried out with real time polymerase chain reaction (RT-PCR), zymographic, Western blotting and immunofluorescence. U937s' migration was enhanced by TNF-α stimulation, while was inhibited by IVIG pretreatment. MMP9 expression and activity in U937s were also significantly enhanced by TNF-α and inhibited by IVIVG pretreatment. During inflammatory stimulus, nuclear factor kappa B (NF-κB) and P38 Mitogenactivated protein kinase (P38 MAPK) pathways play a significant role in regulating MMP9 gene expression. TNF-α induced nuclear translocation of NF-κB and P38 MAPK activation in U937s were inhibited significantly by IVIG. Furthermore, we clarified that nuclear NF-κB and P38 MAPK pathways play pivotal roles in regulating U937s' migration and MMP9 expressions using PDTC and SB203580, which were specific inhibitors of NF-κB and p38 MAPK pathways. IVIG displays striking biological effects, notably promoting monocyte migration. These effects involve the NF-κB and p38 pathways, and increased MMP9 activity. It might be a crucial mechanism of IVIG reducing the occurrence of CAL that IVIG inhibited monocytes expressing MMP9 and decreased chemotactic migration of monocyte.


Is dabigatran cost effective compared with warfarin for stroke prevention in atrial fibrillation? A critically appraised topic.
Warfarin has provided protection against cardioembolic stroke in the setting of nonvalvular atrial fibrillation (NVAF) for the past 60 years. Dabigatran, the first oral direct thrombin inhibitor to be approved in the United States, promises to provide the same or better stroke protection with reduced risk of intracranial hemorrhage. However, it remains to be seen whether grand-scale adoption of dabigatran will be cost effective. To critically assess current evidence regarding the cost effectiveness of dabigatran for preventing stroke in patients with NVAF compared with warfarin. The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of vascular neurology. A cost-effectiveness analysis (CEA) that followed a hypothetical cohort of NVAF patients 65 years of age or older and CHADS2≥1 over their lifetime comparing dabigatran with adjusted-dose warfarin was reviewed. Assuming a willingness to pay a threshold of $50,000 per quality-adjusted life year (QALY), base case results favored high-dose (150 mg bid) dabigatran as a cost-effective alternative to warfarin. Sensitivity analysis asserted that the cost effectiveness of dabigatran improved if it could be obtained for ≤$13/d or if it was used in populations with high risk of stroke or intracranial hemorrhage. Dabigatran 150 mg bid ($12,286 per QALY) is a cost-effective alternative to International Normalized Ratio-adjusted warfarin for the prevention of ischemic stroke in patients 65 years of age or older with NVAF.


Non-replication of an association of Apolipoprotein E2 with sinistrality.
A recent report found that left-handed adolescents were more than three times more likely to have an Apolipoprotein (APOE) ϵ2 allele. This study was unable to replicate this association in young adults (N=166). A meta-analysis of nine other datasets (N=360 to 7559, Power > 0.999) including that of National Alzheimer's Coordinating Center also failed to find an over-representation of ϵ2 among left-handers indicating that this earlier outcome was most likely a statistical artefact.


The Prevalence of Burnout Among Entry-Level Dental Hygiene Program Directors.
Purpose: Workplace burnout in academia is a problem that affects career satisfaction and longevity. The purpose of this study was to determine the prevalence of burnout among entry-level dental hygiene program directors.Methods: The Copenhagen Burnout Inventory (CBI) survey was used to determine prevalence of burnout in 325 dental hygiene program directors from across the United States. The survey was disseminated electronically. The CBI contains 19 questions that measure overall, personal, work-related, and client/student-related burnout on a five-point Likert type scale. The survey also included nine demographic and three open-ended questions related to burnout. Descriptive statistics, one sample t-tests, and one-way ANOVA tests were used to analyze the data.Results: One hundred twenty-seven dental hygiene program directors completed the survey for a 39.1% response rate. Most participants (62.2%, n=79) indicated moderate to high burnout on the personal burnout subscale, approximately one half (51.2%, n=65) on the work-related burnout subscale, and one third (33.1%, n=42) on the client/student-related burnout subscale. No statistically significant differences were found when comparing mean scores between directors of two-year and four-year program or between participants under age 50 and those 50 years of age and older (p-values>0.05). Program directors with teaching workloads of 51-60% had significantly lower burnout on the work-related burnout subscale when compared to participants with teaching workloads of 31-40% (p=0.045). Participants with the lowest workload allocations for administrative duties had higher overall mean burnout scores.Conclusion: Results from this study suggest one out of two dental hygiene program directors have symptoms of some type of burnout with the highest prevalence rate in the personal burnout subscale. Findings underscore the need for further research to identify stressors that lead to burnout as well as identify prevention strategies that promote a healthier work climate for dental hygiene program administrators.


Thoracic Spinal Cord Stimulation for Heart Failure as a Restorative Treatment (SCS HEART study): first-in-man experience.
Preclinical studies suggest that neuromodulation with thoracic spinal cord stimulation (SCS) improves left ventricular (LV) function and remodeling in systolic heart failure (HF). The purpose of this study was to evaluate the safety and efficacy of a SCS system for the treatment of systolic HF. We performed a prospective, multicenter pilot trial in patients with New York Heart Association (NYHA) class III HF, left ventricular ejection fraction (LVEF) 20%-35%, and implanted defibrillator device who were prescribed stable optimal medical therapy. Dual thoracic SCS leads were used at the T1-T3 level. The device was programmed to provide SCS for 24 hours per day (50 Hz at pulse width 200 μs). We enrolled 22 patients from 5 centers:17 patients underwent implantation of a SCS device and 4 patients who did not fulfill the study criteria served as nontreated controls. No deaths or device-device interactions were noted during the 6-month period in the 17 SCS-treated patients. Fifteen of 17 completed the efficacy endpoint assessments: composite score improved by 4.2 ± 1.3, and 11 patients (73%) showed improvement in ≥4 of 6 efficacy parameters. There was significant improvement in NYHA class (3.0 vs 2.1, P = .002; 13/17 improved); Minnesota Living with Heart Failure Questionnaire (42 ± 26 vs 27 ± 22, P = .026; 12/17 improved); peak maximum oxygen consumption (14.6 ± 3.3 vs 16.5 ± 3.9 mL/kg/min, P = .013; 10/15 improved); LVEF (25% ± 6% vs 37% ± 8%, P<.001; 14/16 improved); and LV end-systolic volume (174 ± 57 vs 137 ± 37 mL, P = .002; 11/16 improved) but not in N-terminal prohormone brain natriuretic peptide. No such improvements were observed in the 4 nontreated patients. The results of this first-in-human trial suggest that high thoracic SCS is safe and feasible and potentially can improve symptoms, functional status, and LV function and remodeling in patients with severe, symptomatic systolic HF.


Multicopy tRNA genes functionally suppress mutations in yeast eIF-2 alpha kinase GCN2: evidence for separate pathways coupling GCN4 expression to unchanged tRNA.
GCN2 is a protein kinase that stimulates translation of GCN4 mRNA in amino acid-starved cells by phosphorylating the alpha subunit of translation initiation factor 2 (eIL-2). We isolated multicopy plasmids that overcome the defective derepression of GCN4 and its target genes caused by the leaky mutation gcn2-507. One class of plasmids contained tRNA(His) genes and conferred efficient suppression only when cells were starved for histidine; these plasmids suppressed a gcn2 deletion much less efficiently than they suppressed gcn2-507. This finding indicates that the reduction in GCN4 expression caused by gcn2-507 can be overcome by elevating tRNA(His) expression under conditions in which the excess tRNA cannot be fully aminoacylated. The second class of suppressor plasmids all carried the same gene encoding a mutant form of tRNA(Val) (AAC) with an A-to-G transition at the 3' encoded nucleotide, a mutation shown previously to reduce aminoacylation of tRNA(Val) in vitro. In contrast to the wild-type tRNA(His) genes, the mutant tRNA(Val) gene efficiently suppressed a gcn2 deletion, and this suppression was independent of the phosphorylation site on eIF-2 alpha (Ser-51). Overexpression of the mutant tRNA(Val) did, however, stimulate GCN4 expression at the translational level. We propose that the multicopy mutant tRNA(Val) construct leads to an accumulation of uncharged tRNA(Val) that derepresses GCN4 translation through a pathway that does not involve GCN2 or eIF-2 alpha phosphorylation. This GCN2-independent pathway was also stimulated to a lesser extent by the multicopy tRNA(His) constructs in histidine-deprived cells. Because the mutant tRNA(Val) exacerbated the slow-growth phenotype associated with eIF-2 alpha hyperphosphorylation by an activated GCN2c kinase, we suggest that the GCN2-independent derepression mechanism involves down-regulation of eIF-2 activity.


Species delimitation in native South American fire ants.
The taxonomy of fire ants has been plagued by difficulties in recognizing species on the basis of morphological characters. We surveyed allozyme markers and sequences of the mtDNA COI gene in several closely related nominal species from two areas of sympatry in the native ranges to learn whether the morphology-based delimitation of these species is supported by genetic data. We found that Solenopsis invicta and Solenopsis richteri, pest species whose distinctiveness has been debated, appear to be fully reproductively isolated at both study sites. This isolation contrasts with the extensive hybridization occurring between them in the USA, where both have been introduced. We also found strong genetic differentiation consistent with barriers to gene flow between Solenopsis quinquecuspis and the other two species. However, several lines of evidence suggest that nuclear and mitochondrial genes of S. invicta and S. richteri are introgressing into S. quinquecuspis. The latter apparently is a recently derived member of the clade that includes all three species, suggesting that there has been insufficient time for its full development of intrinsic isolating mechanisms. Finally, our discovery of genetically distinct populations within both S. invicta and S. richteri suggests the presence of previously unrecognized (cryptic) species. Their existence, together with the difficulties in developing diagnostic morphological characters for described species, imply that the group is actively radiating species and that morphological divergence generally does not keep pace with the development of reproductive isolation and neutral genetic divergence in this process.


Effective isolation of retrotransposons and repetitive DNA families from the wheat genome.
New classes of repetitive DNA elements were effectively identified by isolating small fragments of the elements from the wheat genome. A wheat A genome library was constructed from Triticum monococcum by degenerate cleavage with EcoO109I, the recognition sites of which consisted of 5'-PuGGNCCPy-3' multi-sequences. Three novel repetitive sequences pTm6, pTm69 and pTm58 derived from the A genome were screened and tested for high copy number using a blotting approach. pTm6 showed identity with integrase domains of the barley Ty1-Copia-retrotransposon BARE-1 and pTm58 showed similarity to the barley Ty3-gypsy-like retrotransposon Romani. pTm69, however, constituted a tandem array with useful genomic specificities, but did not share any identity with known repetitive elements. This study also sought to isolate wheat D-genome-specific repetitive elements regardless of the level of methylation, by genomic subtraction. Total genomic DNA of Aegilops tauschii was cleaved into short fragments with a methylation-insensitive 4 bp cutter, MboI, and then common DNA sequences between Ae. tauschii and Triticum turgidum were subtracted by annealing with excess T. turgidum genomic DNA. The D genome repetitive sequence pAt1 was isolated and used to identify an additional novel repetitive sequence family from wheat bacterial artificial chromosomes with a size range of 1 395-1 850 bp. The methods successfully led pathfinding of two unique repetitive families.


Manipulating the interfacial structure of nanomaterials to achieve a unique combination of strength and ductility.
The control of interfaces in engineered nanostructured materials has met limited success compared with that which has evolved in natural materials, where hierarchical structures with distinct interfacial states are often found. Such interface control could mitigate common limitations of engineering nanomaterials. For example, nanostructured metals exhibit extremely high strength, but this benefit comes at the expense of other important properties like ductility. Here, we report a technique for combining nanostructuring with recent advances capable of tuning interface structure, a complementary materials design strategy that allows for unprecedented property combinations. Copper-based alloys with both grain sizes in the nanometre range and distinct grain boundary structural features are created, using segregating dopants and a processing route that favours the formation of amorphous intergranular films. The mechanical behaviour of these alloys shows that the trade-off between strength and ductility typically observed for metallic materials is successfully avoided here.


[Pathological restructuring of compact bone tissue as evidenced by detailed x-rays of hands].
The author analyzes precise roentgenograms of the hands in more than 250 patients with diseases of the skeleton, resultant from dysmetabolism. He emphasizes the similarity between juxta-endosteal and intracortical resorption of compact bone tissue at some sites of the compact matter. Three degrees of intracortical resorption are distinguished and its relationship to the blood parathyroid hormone level revealed. Both the intracortical and the juxta-endosteal resorption reflect the accelerated rate of bone tissue restructuring along the Haversian surfaces. The markedness of these resorption types depends on the specific features of the productive phase of restructuring as well. Intracortical resorption reflects the reversible and the juxta-endosteal resorption the irreversible bone tissue loss. The latter resorption type is associated with accelerated loss of compact matter. Laminar stratification and spongious degeneration of the compact matter in the juxta-endosteal zone is the most marked not in osteoporosis, but in osteomalacia and hyperparathyroid osteodystrophy. Intracortical resorption is valuable for the differential diagnosis of osteomalacia and hyperparathyroid osteodystrophy with osteoporosis in subjects aged under 50; in older persons irreversible loss of compact matter predominates and osteoporosis of the peripheral skeleton is therefore particularly marked.


Urinary testosterone and epitestosterone excretions in women with idiopathic hirsutism.
Urinary testosterone and epitestosterone were determined in 90 normal healthy women and in 90 women with idiopathic hirsutism, both groups aged between 16 and 46 years. Testosterone and epitestosterone excretion values were above the normal range in 27 of the 90 hirsute women (30%), and these 27 women had much more prominent hair growth than the others. When these results were statistically analysed according to the age groups or for all ages as a whole, they were found to be highly significant (P less than 0.0005). Therefore, it is concluded that the estimation of urinary testosterone and epitestosterone could be meaningfully applied to study the androgen status of hirsute women.


Three-Dimensional Lead Iodide Perovskitoid Hybrids with High X-ray Photoresponse.
Large organic A cations cannot stabilize the 3D perovskite AMX3 structure because they cannot be accommodated in the cubo-octhedral cage (do not follow the Goldschmidt tolerance factor rule), and they generally template low-dimensional structures. Here we report that the large dication aminomethylpyridinium (AMPY) can template novel 3D structures which resemble conventional perovskites. They have the formula (xAMPY)M2I6 (x = 3 or 4, M = Sn2+ or Pb2+) which is double of the AMX3 formula. However, because of the steric requirement of the Goldschmidt tolerance factor rule, it is impossible for (xAMPY)M2I6 to form proper perovskite structures. Instead, a combination of corner-sharing and edge-sharing connectivity is adopted in these compounds leading to the new 3D structures. DFT calculations reveal that the compounds are indirect band gap semiconductors with direct band gaps presenting at slightly higher energies and dispersive electronic bands. The indirect band gaps of the Sn and Pb compounds are ∼1.7 and 2.0 eV, respectively, which is slightly higher than the corresponding AMI3 3D perovskites. The Raman spectra for the compounds are diffuse, with a broad rising central peak at very low frequencies around 0 cm-1, a feature that is characteristic of dynamical lattices, high anharmonicity, and dissipative vibrations very similar to the 3D AMX3 perovskites. Devices of (3AMPY)Pb2I6 crystals exhibit clear photoresponse under ambient light without applied bias, reflecting a high carrier mobility (μ) and long carrier lifetime (τ). The devices also exhibit sizable X-ray generated photocurrent with a high μτ product of ∼1.2 × 10-4 cm2 /V and an X-ray sensitivity of 207 μC·Gy-1·cm-2.


Recognition of biovar C of Fusobacterium necrophorum (Flügge) Moore and Holdeman as Fusobacterium pseudonecrophorum sp. nov., nom. rev. (ex Prévot 1940).
The cellular morphology, colonial morphology, biochemical properties, DNA base compositions, and DNA-DNA homolgies of three biovars of Fusobacterium necrophorum were examined. Some differences were found among the three biovars in cellular morphology, colonial morphology, and biochemical properties. The guanine-plus-cytosine contents of DNAs from biovar C strains Fn521T (T = type strain), Fn522, and Fn520 were 30.4, 29.3, and 28.0 mol%, respectively, and the guanine-plus-cytosine contents of DNAs from strains VPI 2891 (biovar A) and VPI 6161 (biovar B) were 31.3 and 32.0 mol%, respectively. Labeled DNA from biovar C strain Fn521T exhibited 96 and 82% relatedness to DNAs from biovar C strains Fn522 and Fn520, respectively; however, it exhibited only about 10% relatedness to DNAs from strains of biovars A and B. Labeled DNAs from strains VPI 2891 and VPI 6161 exhibited more than 70% relatedness to each other, but about 6 to 20% relatedness to DNAs from biovar C strains. Therefore, Fusobacterium pseudonecrophorum sp. nov., nom. rev. (ex Prévot 1940) is proposed for Fusobacterium necrophorum biovar C. The type strain is strain Fn521 (= JCM 3722).


A hydrogel based nanosensor with an unprecedented broad sensitivity range for pH measurements in cellular compartments.
Optical pH nanosensors have been applied for monitoring intracellular pH in real-time for about two decades. However, the pH sensitivity range of most nanosensors is too narrow, and measurements that are on the borderline of this range may not be correct. Furthermore, ratiometric measurements of acidic intracellular pH (pH < 4) in living cells are still challenging due to the lack of suitable nanosensors. In this paper we successfully developed a multiple sensor, a fluorophore based nanosensor, with an unprecedented broad measurement range from pH 1.4 to 7.0. In this nanosensor, three pH-sensitive fluorophores (difluoro-Oregon Green, Oregon Green 488, and fluorescein) and one pH-insensitive fluorophore (Alexa 568) were covalently incorporated into a nanoparticle hydrogel matrix. With this broad range quadruple-labelled nanosensor all physiological relevant pH levels in living cells can be measured without being too close to the limits of its pH-range. The nanosensor exhibits no susceptibility to interference by other intracellular ions at physiological concentrations. Due to its positive surface charge it is spontaneously internalized by HeLa cells and localizes to the lysosomes where the mean pH was measured at 4.6. This quadruple-labelled nanosensor performs accurate measurements of fluctuations of lysosomal pH in both directions, which was shown by treatment with the V-ATPase inhibitor bafilomycin A1 or its substrate ATP in HeLa cells. These measurements indicate that this novel quadruple-labelled nanosensor is a promising new tool for measuring the pH of acidic compartments in living cells.


Administration of tauroursodeoxycholic acid (TUDCA) reduces apoptosis following myocardial infarction in rat.
Black bear bile has been used in traditional Chinese medicine to treat liver and eye related illnesses for centuries. A major constituent of bile is ursodeoxycholic acid (UDCA). Recent analysis of the cellular effects of UDCA and its taurine conjugate tauroursodeoxycholic acid (TUDCA) have demonstrated their antiapoptotic properties through regulation of Bcl-2 family and survival signaling proteins (Bax, Bad, phosphatidylinositol-3-kinase). In this study, we tested the hypothesis that TUDCA administered to rats prior to a myocardial infarction (MI) would exhibit anti-apoptotic effects and improve cardiac function. Prior to ligation of the left anterior descending (LAD) coronary artery, TUDCA (50 mg/ml, 400 mg/kg, IV) or PBS was administered to rats. Animals were sacrificed 24 hours after ligation for terminal transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) and caspase-3 activity to assess apoptosis. Additional TUDCA or PBS treated rats underwent pre-operative,1 and 4 week transthoracic ultrasounds to assess heart function by quantification of shortening fraction (SF) and infarct area. TUNEL labeling of the cardiac tissue revealed a significant reduction in apoptotic cells in rats given TUDCA prior to ischemic injury (p = 0.05). In support of reducing apoptosis, caspase-3 activity in the TUDCA treated animals also decreased (p = 0.02). By 4 weeks, a significantly smaller infarct area was present in the TUDCA group compared to the PBS group (0.05 vs. 0.13 cm(2), p = NS) and there was also an improvement in SF. The results provide evidence for TUDCA as a viable treatment for reducing apoptosis in a model of myocardial infarction. Additional studies will distinguish the functional result of improved cell survival following infarction, suggesting the potential for clinical application of this anti-apoptotic drug in treatment of acute MI.


Endoscopic hemithyroidectomy with prophylactic ipsilateral central neck dissection via an unilateral axillo-breast approach without gas insufflation for unilateral micropapillary thyroid carcinoma: preliminary report.
Recently, various endoscopic approaches have been applied to thyroid surgery. However, few specific data exist on endoscopic thyroidectomy with central neck dissection (CND) for micropapillary thyroid carcinoma. This study aimed to evaluate the feasibility and safety of endoscopic hemithyroidectomy (HT) plus CND. In this study, 29 consecutive patients underwent endoscopic HT with ipsilateral CND via a unilateral axillo-breast approach (endo group), and 30 matched control patients underwent conventional open HT with ipsilateral CND (open group). The following variables were compared between these two groups: perioperative complications, surgery-related outcomes, and pathologic outcomes. The operating time in the endo group was longer than in the open group (p = 0.012). In terms of parathyroid gland (PTG) preservation, there were no statistically significant differences between the two groups. The mean numbers of dissected central lymph nodes and metastatic central lymph nodes were similar in the two groups (p = 0.506 vs. 0.975). The endo group had a significantly longer mean hospital stay (6.21 +/- 0.94 days) than the open group (4.30 +/- 1.02 days; p = 0.000). No significant difference was observed in the overall perioperative complications between the two groups. This study demonstrates that the endoscopic approach of CND plus HT is feasible for selected unilateral, intrathyroidal, micropapillary carcinomas. In the future, prospective and comparative studies on the surgical techniques of total thyroidectomy and CND are needed to verify their oncologic safety.


[A limited turbidostat yeast culture under heat shock conditions].
A response of limited turbidostat S. cerevisiae 14 culture on rapid increase in temperature from optimal 30 degrees to supraoptimal 37.5 degrees C. The temporal thermotolerance was absent in glucose and phosphate-limited cultures. Limitation of nitrogen, Mg, betaalanine, biotin, and, to a certain extent, potassium did not decrease the thermotolerance. The pattern of changes in age composition and specific optical density was found to be similar in limited and unlimited cultures. The glucose and phosphate expenditures at 37.5 degrees C were estimated. The response to heat shock was found to depend on the nature of the limiting factor and the extent of limiting.


Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: a systematic review and meta-analysis.
Current guidelines recommend an intravenous bolus dose of a proton pump inhibitor (PPI) followed by continuous PPI infusion after endoscopic therapy in patients with high-risk bleeding ulcers. Substitution of intermittent PPI therapy, if similarly effective as bolus plus continuous-infusion PPI therapy, would decrease the PPI dose, costs, and resource use. To compare intermittent PPI therapy with the currently recommended bolus plus continuous-infusion PPI regimen for reduction of ulcer rebleeding. Searches included MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases through December 2013; US and European gastroenterology meeting abstracts from 2009 to 2013; and bibliographies of systematic reviews. Randomized trials of patients with endoscopically treated high-risk bleeding ulcers (active bleeding, nonbleeding visible vessels, and adherent clots) comparing intermittent doses of PPIs and the currently recommended regimen (80-mg intravenous bolus dose of a PPI followed by an infusion of 8 mg/h for 72 hours). Duplicate independent data extraction and risk-of-bias assessment were performed. Data were pooled using a fixed-effects model or a random effects model if statistical heterogeneity was present. The primary outcome was rebleeding within 7 days; additional predefined outcomes included rebleeding within 3 and 30 days, need for urgent intervention, mortality, red blood cell transfusion, and length of hospital stay. The primary hypothesis, defined before initiation of the literature review, was that intermittent use of PPIs was noninferior to bolus plus continuous infusion of PPIs, with the noninferiority margin predefined as an absolute risk difference of 3%. The risk ratio of rebleeding within 7 days for intermittent vs bolus plus continuous infusion of PPIs was 0.72 (upper boundary of 1-sided 95% CI, 0.97) and the absolute risk difference was -2.64% (upper boundary of 1-sided 95% CI, -0.28%, which is well below the predefined noninferiority margin of 3%). Risk ratios for rebleeding within 30 days and 3 days, mortality, and urgent interventions were less than 1 and mean differences for blood transfusion and hospital length of stay were less than 0, indicating that no summary estimate showed an increased risk with intermittent therapy. The upper boundaries of 95% CIs for absolute risk differences were less than 1.50% for all predefined rebleeding outcomes. Intermittent PPI therapy is comparable to the current guideline-recommended regimen of intravenous bolus plus a continuous infusion of PPIs in patients with endoscopically treated high-risk bleeding ulcers. Guidelines should be revised to recommend intermittent PPI therapy.


[Physiological changes in fruits and vegetables sensitive to cold].
The main external manifestations of chilling injury and the critical temperatures at which these manifestations appear in certain fruits and vegetables are described. Several hypothesis about its origin are indicated as follows: phase change in mitochondrial membranes, increase in the organic acids content, modification of enzyme activities, accumulation of toxic metabolites and alterations in the oxidative phosphorylation process. It is concluded that the physiological changes in the post-recollection period of fruits and vegetables, sensitive to chilling injury, need to be further investigated.


Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.
In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.


Burden of gastrointestinal disease in the United States: 2012 update.
Gastrointestinal (GI) diseases account for substantial morbidity, mortality, and cost. Statistical analyses of the most recent data are necessary to guide GI research, education, and clinical practice. We estimate the burden of GI disease in the United States. We collected information on the epidemiology of GI diseases (including cancers) and symptoms, along with data on resource utilization, quality of life, impairments to work and activity, morbidity, and mortality. These data were obtained from the National Ambulatory Medical Care Survey; National Health and Wellness Survey; Nationwide Inpatient Sample; Surveillance, Epidemiology, and End Results Program; National Vital Statistics System; Thompson Reuters MarketScan; Medicare; Medicaid; and the Clinical Outcomes Research Initiative's National Endoscopic Database. We estimated endoscopic use and costs and examined trends in endoscopic procedure. Abdominal pain was the most common GI symptom that prompted a clinic visit (15.9 million visits). Gastroesophageal reflux was the most common GI diagnosis (8.9 million visits). Hospitalizations and mortality from Clostridium difficile infection have doubled in the last 10 years. Acute pancreatitis was the most common reason for hospitalization (274,119 discharges). Colorectal cancer accounted for more than half of all GI cancers and was the leading cause of GI-related mortality (52,394 deaths). There were 6.9 million upper, 11.5 million lower, and 228,000 biliary endoscopies performed in 2009. The total cost for outpatient GI endoscopy examinations was $32.4 billion. GI diseases are a source of substantial morbidity, mortality, and cost in the United States.


Risk estimation for ochratoxin A in European countries.
Ochratoxin A is a mycotoxin produced by fungi occurring frequently on cereals. Their growth, and the associated toxin production, are closely correlated to the degree of moisture to which they are exposed, which itself is dependent on weather conditions at harvest and techniques for drying and storage. Eighteen species of fungi found in foods can produce ochratoxin A; all of these also produce other mycotoxins. The distribution of these mycotoxins in foods, which probably differs according to climate, has not yet been studied. The lowest doses of ochratoxin A that are toxic in experimental animals are four to five times higher than those found even in hyperendemic regions. This finding casts doubt on the hypothesis that ochratoxin A is the sole cause of Balkan endemic nephropathy and renal tumours. It is therefore not possible to estimate the risk from this mycotoxin for Europe or for individual European countries. Data on the occurrence of both ochratoxin A and other toxins and on the quantities consumed should be collected systematically; these can then be used to assess post-harvest techniques.


The effects of slow breathing on affective responses to pain stimuli: an experimental study.
This study examined whether breathing rate affected self-reported pain and emotion following thermal pain stimuli in women with fibromyalgia syndrome (FM: n=27) or age-matched healthy control women (HC: n=25). FM and HC were exposed to low and moderate thermal pain pulses during paced breathing at their normal rate and one-half their normal rate. Thermal pain pulses were presented in four blocks of four trials. Each block included exposure to both mild and moderate pain trials, and periods of both normal and slow paced breathing. Pain intensity and unpleasantness were recorded immediately following each pain trial, and positive and negative affect were assessed at the end of each block of trials. Compared to normal breathing, slow breathing reduced ratings of pain intensity and unpleasantness, particularly for moderately versus mildly painful thermal stimuli. The effects of slow breathing on pain ratings were less reliable for FM patients than for HCs. Slow versus normal breathing decreased negative affect ratings following thermal pain pulses for both groups, and increased positive affect reports, but only for healthy controls with high trait negative affect. Participants who reported higher levels of trait positive affect prior to the experiment showed greater decreases in negative affect as a result of slow versus normal breathing. These experimental findings provide support for prior reports on the benefits of yogic breathing and mindful Zen meditation for pain and depressed affect. However, chronic pain patients may require more guidance to obtain therapeutic benefit from reduced breathing rates.


Can patient decision aids reduce decisional conflict in a de-escalation of breast radiotherapy clinical trial? The PRIMETIME Study Within a Trial implemented using a cluster stepped-wedge trial design.
For patients with early breast cancer considered at very-low risk of local relapse, risks of radiotherapy may outweigh the benefits. Decisions regarding treatment omission can lead to patient uncertainty (decisional conflict), which may be lessened with patient decision aids (PDA). PRIMETIME (ISRCTN 41579286) is a UK-led biomarker-directed study evaluating omission of adjuvant radiotherapy in breast cancer; an embedded Study Within A Trial (SWAT) investigated whether PDA reduces decisional conflict using a cluster stepped-wedge trial design. PDA diagrams and a video explaining risks and benefits of radiotherapy were developed in close collaboration between patient advocates and PRIMETIME trialists. The SWAT used a cluster stepped-wedge trial design, where each cluster represented the radiotherapy centre and referring peripheral centres. All clusters began in the standard information group (patient information and diagrams) and were randomised to cross-over to the enhanced information group (standard information plus video) at 2, 4 or 6 months. Primary endpoint was the decisional conflict scale (0-100, higher scores indicating greater conflict) which was assessed on an individual participant level. Multilevel mixed effects models used a random effect for cluster and a fixed effect for each step to adjust for calendar time and clustering. Robust standard errors were also adjusted for the clustering effect. Five hundred twenty-one evaluable questionnaires were returned from 809 eligible patients (64%) in 24 clusters between April 2018 and October 2019. Mean decisional conflict scores in the standard group (N = 184) were 10.88 (SD 11.82) and 8.99 (SD 11.82) in the enhanced group (N = 337), with no statistically significant difference [mean difference - 1.78, 95%CI - 3.82-0.25, p = 0.09]. Compliance with patient information and diagrams was high in both groups although in the enhanced group only 121/337 (36%) reported watching the video. The low levels of decisional conflict in PRIMETIME are reassuring and may reflect the high-quality information provision, such that not everyone required the video. This reinforces the importance of working with patients as partners in clinical trials especially in the development of patient-centred information and decision aids.


Cost-effectiveness of scheduled maintenance treatment with infliximab for pediatric Crohn's disease.
Infliximab recently became the only biologic approved for use in pediatric patients with severe active Crohn's disease (CD). To estimate the cost-effectiveness of scheduled maintenance treatment with infliximab compared with standard care in children suffering from severe active CD over 5 years from the UK National Health Service perspective. A Markov model was constructed to simulate the progression of a hypothetical cohort of CD children through predefined health states on scheduled maintenance treatment with infliximab (5 mg/kg). The data to populate the model came from infliximab trials from Targan et al., ACCENT I, and REACH. The health states included in the model were remission, responding active disease, nonresponding active disease, surgery, postsurgery remission, postsurgery complications, and death. Standard care, comprising immunomodulators, and/or corticosteroids were used as a comparator. The primary outcome was quality-adjusted life-years (QALY) estimated using the EuroQol (EQ-5D) from a European CD population. To account for the weight-based dosing of infliximab, a baseline patient weight of 40 kg that increased by 5 kg/year up to 60 kg was used. The costs and outcomes were discounted at 3.5% over a period of 5 years. Probabilistic sensitivity analyses were performed by varying the infliximab efficacy estimates, costs, and utilities. The incremental cost-effectiveness ratio (ICER) for infliximab treatment was pound14,607 compared with standard care. The sensitivity analyses revealed the treatment effect of infliximab to be the most influential parameter with ICERs ranging from pound10,480 to pound37,017. Assuming a willingness to pay of pound30,000 per QALY, the probability of infliximab being cost-effective is 78.6%. Scheduled maintenance treatment with infliximab (5 mg/kg) is likely to be a cost-effective treatment in children suffering from severe active CD under an 8-week maintenance program.


Toward improved empiric management of moderate to severe urinary tract infections.
Guidelines to show whether a patient hospitalized because of a urinary tract infection (UTI) has a severe infection, and whether he or she is at high risk for harboring a multiresistant pathogen, are scant. The aims of the present study were to find (1) clinical and laboratory variables known within 24 hours of admission that, combined in a logistic model, will point to a high or low probability of bacteremia and (2) variables that can be used to define patients at high risk for the subsequent isolation of a multiresistant uropathogen. In a set of patients consecutively admitted to a department of medicine because of UTI, we compared bacteremic vs nonbacteremic patients, and patients with a multiresistant uropathogen vs others, on logistic regression analysis. The logistic models derived were validated in a second set of patients with UTI. Among 247 patients with UTI (median age, 75 years), 80 of them with bacteremia, five factors were significantly and independently associated with bacteremia: serum creatinine level, leukocyte count, temperature, diabetes mellitus, and low serum albumin level. A logistic model incorporating those factors was used to divide the patients into three groups with increasing prevalence of bacteremia (6%, 39%, and 69%) and of death (3%, 6%, and 20%). Three factors were predictive of the subsequent isolation of a resistant uropathogen: use of antibiotics before admission, advanced age, and male gender. The combination of those factors was used to divide patients into two groups, with resistance to cefuroxime of 9% vs 28%, to gentamicin of 7% vs 20%, and to sulfamethoxazole-trimethoprim of 30% vs 50%. In a second set of 144 patients with UTI, the percentages of bacteremia in the three groups were 5%, 16%, and 55%, and those of death, 2%, 6%, and 17%. When divided by the second model, the resistance to cefuroxime in the two groups was 16% vs 30%; to gentamicin, 16% vs 28%; and to sulfamethoxazole-trimethoprim, 28% vs 59%. If prospectively validated in other settings, the models can be used to define groups of patients with UTI at low and high risk for bacteremia, and to help in the choice of empiric antibiotic treatment.


Prognostic significance and clinical importance of estrogen receptor alpha and beta in human endometrioid adenocarcinomas.
Human endometrial cancer expresses both the known estrogen receptors (ER-alpha and ER-beta). The significance of the relative expression of both ER subtypes in endometrial adenocarcinomas remains to be clarified and the usefulness of the determination of the receptor status in endometrial cancer patients is still controversially discussed. Therefore, the aims of this study were the evaluation of the expression patterns of ER-alpha and ER-beta with the characterization of the prognostic significance in uterine endometrioid adenocarcinomas. Pathological and surgical records of 214 patients who were diagnosed with an endometrioid adenocarcinoma without other histological types (including mucinous, mixed, squamous or villoglandular differentiation) were reviewed for both estrogen receptors. The expression of both estrogen receptors was demonstrated in malignant endometrioid adenocarcinomas. ER-alpha was associated with histological differentiation, while ER-beta demonstrated an association with ovarial invasion. The loss of receptor positivity for ER-alpha resulted in a poorer cause-specific survival in endometrial cancer patients, while ER-beta did not affect survival. Interestingly, metastatic patients who expressed ER-alpha or ER-beta had a better survival outcome than estrogen receptor negative patients. Moreover, when tumor samples of affected patients expressed ER-alpha, they had a better cause-specific survival compared to negative findings regarding both estrogen receptors. However, ER-alpha and ER-beta were not independent factors with survival in endometrial adenocarcinoma patients. Therefore, the analysis of both estrogen receptors might be used as a marker to identify high-risk patients only in a subset of patients with endometrioid adenocarcinoma.


Multivariate predictors of failure after flap coverage of pressure ulcers.
Pressure ulcers are estimated to be present in more than one-third of patients with spinal cord injury. The rate of recurrence after flap surgery over last 50 years has ranged between 3 and 82 percent, with no trend toward improvement. This study seeks to identify and evaluate patient and operative characteristics associated with flap dehiscence and ulcer recurrence. A retrospective chart review of all patients who underwent pressure ulcer flap coverage between 1993 and 2008 was performed. Thirty-one demographic and operative variables were collected. Multivariate logistic regression with generalized estimating equation was used to evaluate the effect of significant variables. The primary outcome was recurrence of pressure ulcer at the operative site. Secondary outcomes included flap line dehiscence and the need for operative revision. There were 88 recurrences of pressure ulcers after flap surgery (39 percent) of 227 operations performed on 135 patients. Thirty-six flaps (16 percent) had dehiscences necessitating return to the operating room. Hemoglobin A1c less than 6 percent and previous same-site flap failure were associated with both dehiscence and recurrence (odds ratios, 2.15 and 3.84; and odds ratios, 6.51 and 3.27). Younger age and albumin less than 3.5 were associated with early flap failure (odds ratios, 5.95 and 2.45). Ischial wound location correlated with late recurrence (odds ratio, 4.01). Patients with multiple risk factors had operative success rates that approached zero. Confirmation of adequate nutritional status and strict preoperative management of blood glucose may improve operative success rates. The authors propose that operative management should be approached with trepidation, if at all, in young patients with recurrent ischial ulcers.


Gene silencing in the therapy of influenza and other respiratory diseases: Targeting to RNase P by use of External Guide Sequences (EGS).
Respiratory diseases provide an attractive target for gene silencing using small nucleic acids since the respiratory epithelium can be reached by inhalation therapy. Natural surfactant appears to facilitate the uptake and distribution of these types of molecules making aerosolized nucleic acids a possible new class of therapeutics. This article will review the rationale for the use of External Guide Sequence (EGS) in targeting specific mRNA molecules for RNase P-mediated intracellular destruction. Specific destruction of target mRNA results in gene-specific silencing similar to that instigated by siRNA via the RISC complex. The application of EGS molecules specific for influenza genes are discussed as well as the potential for synergy with siRNA. Furthermore, EGS could be adapted to target other respiratory diseases of viral etiology as well as conditions such as asthma.


The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study.
This study aimed to evaluate the response to and safety of an 8-day course of sapropterin dihydrochloride (6R-tetrahydrobiopterin or 6R-BH4) 10 mg/kg per day in patients with phenylketonuria (PKU), who have elevated blood phenylalanine (Phe) levels, and to identify a suitable cohort of patients who would respond to sapropterin dihydrochloride treatment with a reduction in blood Phe level. Eligible patients were aged > or = 8 years, had blood Phe levels > or = 450 micromol/L and were not adhering to a Phe-restricted diet. Suitable patients were identified by a > or = 30% reduction in blood Phe level from baseline to day 8 following sapropterin dihydrochloride treatment. The proportion of patients who met these criteria was calculated for the overall population and by baseline Phe level (< 600, 600 to < 900, 900 to < 1200 and > or = 1200 micromol/L). In total, 485/490 patients completed the study and 20% (96/485) were identified as patients who would respond to sapropterin dihydrochloride. A reduction in Phe level was observed in all subgroups, although response was greater in patients with lower baseline Phe levels. Wide variability in response was seen across all baseline Phe subgroups. The majority of adverse events were mild and all resolved without complications. Sapropterin dihydrochloride was well tolerated and reduced blood Phe levels across all PKU phenotypes tested. Variability in reduction of Phe indicates that the response to sapropterin dihydrochloride cannot be predicted by baseline Phe level.


Anisotropic united atom model including the electrostatic interactions of benzene.
An optimization including electrostatic interactions has been performed for the parameters of an anisotropic united atoms intermolecular potential for benzene for thermodynamic and transport property prediction using Gibbs ensemble, isothermal-isobaric (NPT) Monte Carlo, and molecular dynamic simulations. The optimization procedure is based on the minimization of a dimensionless error criterion incorporating various thermodynamic data (saturation pressure, vaporization enthalpy, and liquid density) at ambient conditions and at 350 and 450 K. A comprehensive comparison of the new model is given with other intermolecular potentials taken from the literature. Overall thermodynamic, structural, reorientational, and translational dynamic properties of our optimized model are in very good agreement with experimental data. The new model also provides a good representation of the liquid structure, as revealed by three-dimensional spatial density functions and carbon-carbon radial distribution function. Shear viscosity variations with temperature and pressure are very well reproduced, revealing a significant improvement with respect to nonpolar models.


Enjoying the violence of war: Association with posttraumatic symptomatology in U.S. combat veterans.
Engaging in war-related violence can have a devastating impact on military personnel, with research suggesting that injuring or killing others can contribute to posttraumatic stress disorder (PTSD), depression, and moral injury. However, there is also evidence that perpetrating violence in war can become pleasurable to a substantial number of combatants and that developing this "appetitive" form of aggression can diminish PTSD severity. Secondary analyses were conducted on data from a study of moral injury in U.S., Iraq, and Afghanistan combat veterans, to examine the impact of recognizing that one enjoyed war-related violence on outcomes of PTSD, depression, and trauma-related guilt. Three multiple regression models evaluated the impact of endorsing the item, "I came to realize during the war that I enjoyed violence" on PTSD, depression, and trauma-related guilt, after controlling for age, gender, and combat exposure. Results indicated that enjoying violence was positively associated with PTSD, β (SE) = 15.86 (3.02), p < .001, depression, β (SE) = 5.41 (0.98), p < .001, and guilt, β (SE) = 0.20 (0.08), p < .05. Enjoying violence moderated the relationship between combat exposure and PTSD symptoms, β (SE) = -0.28 (0.15), p < .05, such that there was a decrease in the strength of the relationship between combat exposure and PTSD in the presence of endorsing having enjoyed violence. Implications for understanding the impact of combat experiences on postdeployment adjustment, and for applying this understanding to effectively treating posttraumatic symptomatology, are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


The spectrum of epilepsy in children with 15q13.3 microdeletion syndrome.
To further define the epilepsy phenotype in a cohort of children with 15q13.3 microdeletion syndrome. We retrospectively reviewed the phenotypic spectrum of all children aged < 18 years with epilepsy and 15q13.3 microdeletion syndrome. Thirteen children were included, 69% were female. The median age of children in the cohort was 12 years (age range: 3 years-15 years). Median age at seizure onset was 4 years. Eleven children (85%) had intellectual disability. Nine of 13 children (69%) had a history of typical absence seizures with median age of onset at 5 years (2 had absence status epilepticus). Thirty-one percent (4/13) had focal with impaired awareness non-motor onset seizures. ILAE recognized absence epilepsy syndromes were diagnosed in 6/13 (46%). The remainder were classified as having genetic generalized epilepsies with overlap clinical features, combined or focal epilepsies. Electroencephalogram in the cohort showed generalized (85%) and focal epileptiform discharges (62%) and posterior dominant rhythm slowing (33%). One child had electrical status epilepticus of sleep. Neuroimaging was performed in 5 children (38%) and revealed abnormal findings in 3. Seizures were drug resistant in a third of the cohort. Valproate resulted in seizure freedom in 5 (42%). Oxcarbazepine caused clinical worsening in one child with combined seizure types. Two children tried cannabidiol and one tried the ketogenic diet; neither was effective. The epilepsy phenotype in children with 15q13.3 microdeletion syndrome is defined by childhood onset absence seizures, and may have atypical features such as, early onset absences, persistence into adolescence, status epilepticus, intellectual disability and treatment resistance. Focal seizures and focal EEG findings may be observed and should be treated cautiously, given the possibility of combined seizure types. Valproate appeared effective, although other treatments must be explored further.


Brazilian healthy eating index revised (BHEI-R) of women before and during adjuvant treatment for breast cancer.
Different therapeutic modalities for cancer trigger side effects that affect the selection of food by changing dietary patterns. To evaluate changes in the diet quality of women in adjuvant treatment for breast cancer. Sociodemographic, clinical and anthropometric data of 78 women were collected. The Brazilian Healthy Eating Index Revised and its components were obtained from food frequency questionnaire applied before and after the treatment. At baseline, participants were classified according to tertiles of diet quality. The score of the Brazilian Healthy Eating Index Revised (BHEI-R) in the lowest tertile was 48.4 to 75.2 points, the second tertile was 75.7 to 81.8 points, and the upper tertile was 82.0 to 95.7 points. During treatment, of the women classified in the first tertile, 62% improved their diet score quality passing to the upper tertiles. Women classified in the second tertile, did not significantly alter the diet quality during the treatment, although 46% went to the third tertile. Patients classified in the third tertile significantly reduced the average score of the Index by 7.3 points during the treatment. Among these women, 38% and 20% decreased their score for the second and first tertiles respectively, where the reduction in the diet quality was due to reducing the score of components Total fruits, Total vegetables, Dark Green and orange vegetables and Legumes, Total grains and Solid fats, Alcohol and Added sugar. Dietary changes, which were observed after breast cancer diagnosis, significantly altered the quality of diet among the women participating in the study. Future nutrition interventions are important to aid in food choices during the treatment.


Estimating the Cost Savings of Preventive Dental Services Delivered to Medicaid-Enrolled Children in Six Southeastern States.
To quantify the impact of multiyear utilization of preventive dental services on downstream dental care utilization and expenditures for children. We followed 0.93 million Medicaid-enrolled children who were 3-6 years old in 2005 from 2005 to 2011. We used Medicaid claims data of Alabama, Georgia, Mississippi, North Carolina, South Carolina, and Texas. We clustered each state's study population into four groups based on utilization of topical fluoride and dental sealants before caries-related treatment using machine learning algorithms. We evaluated utilization rates and expenditures across the four groups and quantified cost savings of preventive care for different levels of penetration. We extracted all dental-related claims using CDT codes. In all states, Medicaid expenditures were much lower for children who received topical fluoride and dental sealants before caries development than for all other children, with a per-member per-year difference ranging from $88 for Alabama to $156 for Mississippi. The cost savings from topical fluoride and sealants across the six states ranged from $1.1M/year in Mississippi to $12.9M/year in Texas at a 10 percent penetration level. Preventive dental care for children not only improves oral health outcomes but is also cost saving.


Blood Pressure Effects of Sodium Reduction: Dose-Response Meta-Analysis of Experimental Studies.
The relationship between dietary sodium intake and blood pressure (BP) has been tested in clinical trials and nonexperimental human studies, indicating a direct association. The exact shape of the dose-response relationship has been difficult to assess in clinical trials because of the lack of random-effects dose-response statistical models that can include 2-arm comparisons. After performing a comprehensive literature search for experimental studies that investigated the BP effects of changes in dietary sodium intake, we conducted a dose-response meta-analysis using the new 1-stage cubic spline mixed-effects model. We included trials with at least 4 weeks of follow-up; 24-hour urinary sodium excretion measurements; sodium manipulation through dietary change or supplementation, or both; and measurements of systolic and diastolic BP at the beginning and end of treatment. We identified 85 eligible trials with sodium intake ranging from 0.4 to 7.6 g/d and follow-up from 4 weeks to 36 months. The trials were conducted in participants with hypertension (n=65), without hypertension (n=11), or a combination (n=9). Overall, the pooled data were compatible with an approximately linear relationship between achieved sodium intake and mean systolic as well as diastolic BP, with no indication of a flattening of the curve at either the lowest or highest levels of sodium exposure. Results were similar for participants with or without hypertension, but the former group showed a steeper decrease in BP after sodium reduction. Intervention duration (≥12 weeks versus 4 to 11 weeks), type of study design (parallel or crossover), use of antihypertensive medication, and participants' sex had little influence on the BP effects of sodium reduction. Additional analyses based on the BP effect of difference in sodium exposure between study arms at the end of the trial confirmed the results on the basis of achieved sodium intake. In this dose-response analysis of sodium reduction in clinical trials, we identified an approximately linear relationship between sodium intake and reduction in both systolic and diastolic BP across the entire range of dietary sodium exposure. Although this occurred independently of baseline BP, the effect of sodium reduction on level of BP was more pronounced in participants with a higher BP level.


The RGG/RG motif of AUF1 isoform p45 is a key modulator of the protein's RNA chaperone and RNA annealing activities.
The RNA-binding protein AUF1 regulates post-transcriptional gene expression by affecting the steady state and translation levels of numerous target RNAs. Remodeling of RNA structures by the largest isoform AUF1 p45 was recently demonstrated in the context of replicating RNA viruses, and involves two RNA remodeling activities, i.e. an RNA chaperone and an RNA annealing activity. AUF1 contains two non-identical RNA recognition motifs (RRM) and one RGG/RG motif located in the C-terminus. In order to determine the functional significance of each motif to AUF1's RNA-binding and remodeling activities we performed a comprehensive mutagenesis study and characterized the wildtype AUF1, and several variants thereof. We demonstrate that each motif contributes to efficient RNA binding and remodeling by AUF1 indicating a tight cooperation of the RRMs and the RGG/RG motif. Interestingly, the data identify two distinct roles for the arginine residues of the RGG/RG motif for each RNA remodeling activity. First, arginine-mediated stacking interactions promote AUF1's helix-destabilizing RNA chaperone activity. Second, the electropositive character of the arginine residues is the major driving force for the RNA annealing activity. Thus, we provide the first evidence that arginine residues of an RGG/RG motif contribute to the mechanism of RNA annealing and RNA chaperoning.