Male obesity is associated with changed spermatozoa Cox4i1 mRNA level and altered seminal vesicle fluid composition in a mouse model.
The rate of obesity among men of reproductive age has tripled in the last three decades. Previously, we demonstrated that paternal obesity resulted in impaired preimplantation developmental kinetics, compromised post-compaction metabolism and decreased blastocyst cell number when embryos were generated in vivo. Subsequently, using in vitro fertilization we found embryos of obese males to have altered metabolism before compaction, reduced inner cell mass cell number and retarded fetal development--the difference between these two studies being the method of embryo generation and the presence or absence of seminal plasma, respectively. Here, we hypothesize that both sperm and seminal plasma are affected by obesity, compromising embryogenesis and pregnancy health in a cumulative manner. Epididymal sperm and seminal vesicle fluid were collected from normal and obese C57BL/6 mice. RNA and DNA were extracted from spermatozoa for qPCR and global methylation analysis, respectively. Proteomic (Luminex) and metabolomic (GC-MS) techniques were employed to analyse the composition of seminal vesicle fluid. Nuclear encoded cytochrome c oxidase subunit IV isoform 1 (Cox4i1) of the terminal enzyme in the mitochondrial respiratory chain demonstrated significantly increased RNA levels in the sperm of obese males (P< 0.05). Quantitative seminal plasma analysis identified significant changes in levels of the hormones insulin, leptin and estradiol between normal and obese males (P < 0.05). Further, the metabolite composition of seminal vesicle fluid was significantly affected by obesity. Consequently, this study has determined that obesity affects both sperm and seminal plasma composition. The interaction between sperm and seminal plasma warrants further analysis.


Socioeconomic status, social capital and self-reported unmet health care needs: A population-based study.
The aim of this study was to investigate the associations between socioeconomic status (SES) and self-reported unmet health care needs, taking economic stress, generalized trust in other people and trust in the health care system into account. The 2012 public health survey in Scania was conducted using a postal questionnaire and included 28,029 participants aged 18-80 years. The study was cross-sectional. Associations between SES and unmet health care needs were investigated, adjusting for economic stress and trust in logistic regressions. SES was significantly associated with unmet health care needs. The SES categories of unemployed, on long-term sick leave and unskilled manual workers reported particularly high levels of unmet health care needs. SES differences in unmet needs were attenuated when economic stress and the two dimensions of trust and self-rated health were introduced in multiple analyses. The working population gave a lack of time as the reason for unmet health care needs, whereas those on sick leave or unemployed reported a lack of money. SES differences in self-reported unmet health care needs were observed and these associations were attenuated when economic stress during the past year, generalized trust in other people, trust in the health care system and self-rated health were introduced into the multiple models.


[Effects of Qufeng Tongluo Recipe on proliferation of and TGF-beta1 and IL-6 mRNA expressions in glomerular mesangial cells from rats].
To investigate the effects of Qufeng Tongluo Recipe (QFTLR), a compound of traditional Chinese herbal medicine for dispelling wind and removing obstruction in the meridians, on cell proliferation and expressions of transforming growth factor-beta1 (TGF-beta1) and interleukin-6 (IL-6) mRNAs induced by lippolysaccharide in glomerular mesangial cells from rats. The method of serum pharmacology was used. A total of 32 rats were divided into normal control group, untreated group, QFTLR group and positive control group which also was named Monopril (fosinopril sodium) group. Mesangial proliferative glomerulonephritis was induced by injection of antithymocyte serum in the rats except for the normal control group. Sera of the rats were obtained after corresponding interventions. Lipopolysaccharide-induced proliferation of rat mesangial cells (MCs) cultured in the respective serum-containing media was detected by the method of methyl thiazolyl tetrazolium (MTT) assay, and the expressions of TGF-beta1 and IL-6 mRNAs were analyzed by the method of reverse transcription polymerase chain reaction. Compared with the untreated group, QFTLR showed remarkable inhibitory function on the proliferation of the mesangial cells (P<0.05). The expressions of TGF-beta1 mRNA in mesangial cells were increased in the untreated group, QFTLR group and Monopril group when compared with the normal control group (P<0.01), but the TGF-beta1 mRNA expressions in QFTLR group and in Monopril group were lower than that in the untreated group. The IL-6 mRNA expression could be increased by the LPS stimulation, and it was significantly higher in the other three groups than that in the normal control group, including the untreated group, the Monopril group and the QFTLR group (P<0.01). Compared with the untreated group, the expression of IL-6 mRNA was decreased by QFTLR and Monopril (P<0.01). QFTLR was better than Monopril in inhibiting the proliferation of the mesangial cells and decreasing the expressions of TGF-beta1 and IL-6 mRNAs (P<0.05). QFTLR has great inhibitory effect on mesangial cell proliferation and expressions of TGF-beta1 and IL-6 mRNAs, which may be one of its mechanisms in postponing glomerular sclerosis.


Phytoplankton chlorophyte structure as related to ENSO events in a saline lowland river (Salado River, Buenos Aires, Argentina).
We analyzed the phytoplankton present in the lower sector of the Salado River (Buenos Aires, Argentina) for 10 years (1995-2005) and detected significant changes occurring in chlorophyte abundance and species richness during La Niña event (1998-1999), which period was analyzed throughout the entire basin (main stream and tributaries). We compared the physicochemical and biologic variables between two El Niño-La Niña-Southern Oscillation (ENSO) periods - El Niño (March 1997-January 1998) and La Niña (May 1998-May 1999) - to identify possible indicators of a relationship between climatic anomalies and chlorophyte performance. Chlorophyte density increased during the La Niña. Under normal or extreme hydrologic conditions, mobile (Chlamydomonas spp.) and nonmobile (Monoraphidium spp.) chlorophytes codominated. These species belonged to Reynolds's functional groups X1 and X2, those typical of nutrient-enriched environments. Comparative analyses between El Niño and La Niña periods indicated significant differences in physicochemical (K(+), dissolved polyphenols, particulate reactive phosphorus, alkalinity, pH) and biologic (species diversity and richness, phytoplankton and chlorophyte total densities) variables between the two periods at all basin sites. During the La Niña condition, species richness was greater owing to interconnected shallow lakes and drainage-channel inputs, while the Shannon diversity index was lower because of the high abundance values of Monoraphidium minutum. A detailed analysis of the chlorophytes in the entire basin, indicated that changes in density and species dominance occurred on a regional scale although diverse chlorophyte assemblages were identified in the different sectors of the Salado River basin. After La Niña event, the entire basin had the potential to revert to the previous density values, showing the resilience to global environmental changes and the ability to reestablish the general conditions of stability.


Recommendations of the International Society of Intraoperative Neurophysiology for intraoperative somatosensory evoked potentials.
Intraoperative somatosensory evoked potentials (SEPs) provide dorsal somatosensory system functional and localizing information, and complement motor evoked potentials. Correct application and interpretation require in-depth knowledge of relevant anatomy, electrophysiology, and techniques. It is advisable to facilitate cortical SEPs with total intravenous propofol-opioid or similarly favorable anesthesia. Moreover, SEP optimization is recommended to enhance surgical feedback speed and accuracy by maximizing signal-to-noise ratio (SNR); it consists of selecting highest-SNR peripheral and cortical derivations while omitting low-SNR channels. Confounding factors causing non-surgical SEP reduction should be excluded before issuing a warning. It is advisable to facilitate their identification with peripheral SEP controls and cortical SEP systemic controls whenever possible. Warning criteria should adjust for baseline drift and reproducibility. The recommended adaptive warning criterion is visually obvious amplitude reduction from recent pre-change values and clearly exceeding trial-to-trial variability, particularly when abrupt and focal. Acquisition and interpretation should be done by qualified technical and professional level personnel. Indications for SEP monitoring include intracranial, posterior fossa, and spinal neurosurgery, as well as orthopedic spine, cerebrovascular, and descending aortic surgery. Indications for SEP mapping include sensorimotor cortex and dorsal column midline identification. Future advances could modify current recommendations.


[Prevention of burnout and incidences by coping strategies].
The object of our research is centred around burnout in nurses confronted by the successive and repeated deaths of patients in their care. We propose to study the theoretical links between burnout, coping and alexithymie. Our initial hypothesis is that palliative care formation tends to diminue the characteristics of burn-out, the negative and defensive strategies of coping. On the other hand, the process of palliative and adaptative care education tends to develope more efficient, positive and adaptative strategies of coping. The comparative results of two test groups of nurses, formed and not formed in palliative care are presented.


Use of lyodura for bone augmentation of osseous defects around dental implants.
Lyodura has been used in periodontology and maxillofacial surgery to overcome different clinical conditions. The use of lyodura to induce new bone formation in humans has not been widely reported. The purpose of this article is to describe the use of lyodura as a resorbable barrier to promote bone formation in osseous defects around dental implants. The study group consisted of 22 healthy patients (12 women and 10 men), with a mean age of 32 (range 20 to 45). A total of 44 implants (9 titanium screw-type and 35 hydroxyapatite-coated cylinder implants) were placed. Of these, 27 implants were placed in the maxilla and 17 in the mandible. At 27 extraction sites bony vertical defects were measured on the buccal, lingual, mesial and distal sides of the implant. In the remaining 17 cases, where either immediate or staged implantation was performed, and a dehiscence was present, its vertical length was measured from the alveolar crest. All bony defects were grafted with autogenous bone harvested from the tuberosity. Each site was covered with lyodura. Healing was uneventful; no inflammation, infection, or soft tissue dehiscence was observed. At all extraction sites and in 76% of the dehiscence defects, hard tissue appearing clinically similar to bone completely filled the defect. Of those defects not completely filled, a mean vertical bone increase of 2.5 mm was recorded. A mean vertical bone increase of 2.6 mm was achieved at extraction sites and a mean increase of 2.79 mm was achieved at dehiscence sites. Lyodura can safely and effectively be used for guided bone regeneration at both extraction sites and for dehiscence defects.


ELECTRICAL CONNECTIONS BETWEEN VISUAL CELLS IN THE OMMATIDIUM OF LIMULUS.
When microelectrodes are inserted in two cells of the same ommatidium in Limulus, current applied through the membrane of one cell produces a change in potential across the membrane of both cells. The large spikes recorded from one cell and the small spikes recorded from the other always appear synchronously. However, the small spikes are abolished selectively during the hyperpolarizing response. The discrete waves recorded from eyes adapted to darkness occur simultaneously in cells of the same ommatidium.


Automatic Model Selection for Partially Linear Models.
We propose and study a unified procedure for variable selection in partially linear models. A new type of double-penalized least squares is formulated, using the smoothing spline to estimate the nonparametric part and applying a shrinkage penalty on parametric components to achieve model parsimony. Theoretically we show that, with proper choices of the smoothing and regularization parameters, the proposed procedure can be as efficient as the oracle estimator (Fan and Li, 2001). We also study the asymptotic properties of the estimator when the number of parametric effects diverges with the sample size. Frequentist and Bayesian estimates of the covariance and confidence intervals are derived for the estimators. One great advantage of this procedure is its linear mixed model (LMM) representation, which greatly facilitates its implementation by using standard statistical software. Furthermore, the LMM framework enables one to treat the smoothing parameter as a variance component and hence conveniently estimate it together with other regression coefficients. Extensive numerical studies are conducted to demonstrate the effective performance of the proposed procedure.


[Choice of a class I intravenous anti-arrhythmic drug in severe ventricular arrhythmias].
In the choice of a Class I intravenous antiarhythmic medication for the treatment of threatening ventricular extrasystoles, one must take into account the speed of action of the product, its effects on hemodynamics and conduction as well as its efficacy. The rapidity of action implies the ability to reach, without delay, a therapeutic plasma level which will depend upon the distribution volume and the dose injected. An effective plasma level may be quickly reached following the intravenous administration of lidocain, disopyramide, lorcainide, tocainide and flecainide. All antiarhythmic medications have an unfavorable effect on hemodynamics; xylocain and ajmaline seem to depress the least the left ventricular function, followed by lorcainide. Unfavorable effects on the atrio-ventricular conduction are observed with substances of type IC; the duration of QRS may be affected as well by antiarhythmic medications IA and IC, with a lengthening of QT being mostly noted type IA medications. Comparison of the efficacy of antiarhythmic medications requires a strict methodology and the current data from the literature do not permit to assert with certainty the superiority of one antiarhythmic medication over the others.


Control of time of parturition in pigs.
Injection of prostaglandin (PG) F-2 alpha or its analogues has provided a technique to induce parturition after Day 110 of gestation in the sow. The mean interval from PG injection to parturition ranges from 24 to 28 h, but only 50-60% of the sows farrow during an 8-10 h working day, and as many as 20% of sows may begin parturition before the injection of PG or less than 22 h after the injection. The duration of parturition is positively associated with the incidence of stillbirths and perinatal death so that techniques to reduce the duration of parturition may save piglets. Early parturition has been prevented by feeding sows progestagens, PG synthesis inhibitors and hypothalamic function inhibitors. These compounds were detrimental to piglet survival if they delayed parturition too long after the expected time of parturition. Parturition was delayed in sows up to 1.5 days by altrenogest, 1.6 days by meclofenamic acid, 2.7 days by indomethacin, and 3 days by methallibure without increased incidence of stillborn piglets compared with control sows. Injection of PG after administration of altrenogest or meclofenamic acid was successful in experiments with sows; parturition could be confined to a 5-day working week with no increase in stillborn piglets compared with control sows. Relaxin injected at 48 and 24 h before or only 24 h before injection of PG increased the proportion of sows farrowing 22-32 h after PG to 86.2% compared with sows injected only with PG (53.3%, P less than 0.01). Oxytocin injected 20 h after injection of PG increased the proportion of sows farrowing 20-28 h after PG to 90.4% compared with sows injected only with PG (49.2%, P less than 0.005). Injection of 25-60 i.u. ACTH on Day 110 of gestation did not shorten the length of gestation, but did decrease the incidence of still born piglets by 0.2 piglets/litter (P less than 0.05). An injection of the beta-adrenergic antagonist, carazolol, during labour before the birth of the first piglet decreased the duration of parturition and the incidence of stillborn piglets particularly in primiparous sows (P less than 0.05). Carazolol injected with oxytocin 20 h after injection of PG decreased the interval from PG to parturition by 2 h compared with sows injected with only PG and oxytocin.(ABSTRACT TRUNCATED AT 400 WORDS)


[Vasovagal syncope: from genetic to bedside].
Recent studies suggest vasovagal syncope has a significant heritable component indicating that, at least some forms of vasovagal syncope may have a genetic cause. The beta1-adrenergic receptor is a key cell surface signaling protein expressed in the heart and major determinant of cardiac function. The role of genetics in the phenotypic manifestations of vasovagal syncope is unclear. Here, we report the characteristics of several families with several affected members with vasovagal syncope, as well as the results of several genetic studies exploring the prevalence of polymorphisms in the beta1 adrenergic receptors which may be associated with vasovagal syncope.


Baculovirus genomics.
Baculovirus genomes are covalently closed circles of double stranded-DNA varying in size between 80 and 180 kilobase-pair. The genomes of more than fourty-one baculoviruses have been sequenced to date. The majority of these (37) are pathogenic to lepidopteran hosts; three infect sawflies (Hymenoptera) and one has a mosquito host (Diptera). With this information, general patterns of genome structure and gene content became apparent. Baculovirus open reading frames are tightly packed with minimal intergenic regions and the coding sequences are almost equally distributed over both strands. Baculovirus genes form single transcription units, with early and late transcribed ORFs scattered along the genome. A set of twenty nine core genes is conserved and therefore is characteristic for baculoviruses. Most baculovirus genomes contain multiple homologous regions with repeated sequences and often palindromic motifs, which play a crucial role as enhancers of early transcription and most likely in viral DNA replication. Baculovirus genomes have a certain degree of plasticity, as evidenced from the genomic variations within virus isolates from the field. Recombination events and transposon insertions appear to play a role in the uptake of new genes from co-infecting viruses or from the insect host. This review deals with the structural and functional properties of baculovirus genomes including both conserved and variable genes.


The impact of COVID-19 on children and adolescents' mental health.
Children and adolescents are more susceptible to the formation of mental health issues, since their brains are still developing. The coronavirus disease 19 (COVID-19) pandemic response measures have disrupted daily life and left individuals socially isolated, including children and adolescents. In view of this, this study aimed to give a narrative review of the literature on the pandemic's effects on children's and adolescents' mental health, associated risks, and successful intervention strategies. There are still issues to be resolved to give children and adolescents in many regions of the world with quality, rights-based, and culturally relevant mental health care. It is difficult to predict how the COVID-19 pandemic may affect children's and adolescents' mental health in the short- and long-term. To address the mental and social health needs of children and adolescents after the pandemic, it is urgently necessary to perform longitudinal and developmental studies and introduce evidence-centered action plans and interventions.


[Formula: see text] Neural correlates of socioeconomic status in early childhood: a systematic review of the literature.
It is now established that socioeconomic variables are associated with cognitive, academic achievement, and psychiatric outcomes. Recent years have shown the advance in our understanding of how socioeconomic status (SES) relates to brain development in the first years of life (ages 0-5 years). However, it remains unknown which neural structures and functions are most sensitive to the environmental experiences associated with SES. Pubmed, PsycInfo, and Google Scholar databases from January 1, 2000, to December 31, 2019, were systematically searched using terms "Neural" OR "Neuroimaging" OR "Brain" OR "Brain development," AND "Socioeconomic" OR "SES" OR "Income" OR "Disadvantage" OR "Education," AND "Early childhood" OR "Early development". Nineteen studies were included in the full review after applying all exclusion criteria. Studies revealed associations between socioeconomic and neural measures and indicated that, in the first years of life, certain neural functions and structures (e.g., those implicated in language and executive function) may be more sensitive to socioeconomic context than others. Findings broadly support the hypothesis that SES associations with neural structure and function operate on a gradient. Socioeconomic status is reflected in neural architecture and function of very young children, as early as shortly after birth, with its effects possibly growing throughout early childhood as a result of postnatal experiences. Although socioeconomic associations with neural measures were relatively consistent across studies, results from this review are not conclusive enough to supply a neural phenotype of low SES. Further work is necessary to understand causal mechanisms underlying SES-brain associations.


Incidence of cranial nerve palsy after preoperative embolization of glomus jugulare tumors using Onyx.
The resection of glomus jugulare tumors can be challenging because of their inherent vascularity. Preoperative embolization has been advocated as a means of reducing operative times, blood loss, and surgical complications. However, the incidence of cranial neuropathy associated with the embolization of these tumors has not been established. The authors of this study describe their experience with cranial neuropathy following transarterial embolization of glomus jugulare tumors using ethylene vinyl alcohol (Onyx, eV3 Inc.). The authors retrospectively reviewed all cases of glomus jugulare tumors that had been treated with preoperative embolization using Onyx at their institution in the period from 2006 to 2012. Patient demographics, clinical presentation, grade and amount of Onyx used, degree of angiographic devascularization, and procedural complications were recorded. Over a 6-year period, 11 patients with glomus jugulare tumors underwent preoperative embolization with Onyx. All embolization procedures were completed in one session. The overall mean percent of tumor devascularization was 90.7%. No evidence of nontarget embolization was seen on postembolization angiograms. There were 2 cases (18%) of permanent cranial neuropathy attributed to the embolization procedures (facial nerve paralysis and lower cranial nerve dysfunction). Embolizing glomus jugulare tumors with Onyx can produce a dramatic reduction in tumor vascularity. However, the intimate anatomical relationship and overlapping blood supply between these tumors and cranial nerves may contribute to a high incidence of cranial neuropathy following Onyx embolization.


Model to predict rebleeding following endoscopic therapy for non-variceal upper gastrointestinal hemorrhage.
Following endoscopic therapy, up to 20% of patients with non-variceal upper gastrointestinal hemorrhage experience rebleeding. The aim of the present study was to determine risk factors for recurrent hemorrhage in these patients. This was a retrospective cohort study of consecutive patients admitted to a tertiary care hospital between 1 July 1999 and 30 June 2004, with non-variceal upper gastrointestinal hemorrhage. Patients were evaluated for rebleeding within 30 days of successful therapeutic endoscopy. Using the hospital's endoscopic database, 236 patients were identified. Risk factors were identified using multivariable logistic regression with backward selection. Internal validation was carried out using bootstrapping. Six risk factors were identified: failure to use a proton pump inhibitor post-procedure (P = 0.056), Endoscopically demonstrated bleeding (P = 0.053), peptic ulcer as the bleeding source (P = 0.018), treatment with epinephrine monotherapy (P = 0.0026), post-procedure intravenous or low molecular weight heparin use (P = 0.0014), and moderate or severe cirrhosis (P = 0.032) (PEPTIC). The risk of rebleeding increased as the number of risk factors present increased. The observed rates of rebleeding were: 7.1%, 16.4%, 37.0%, 75.0% and 100% for zero, one, two, three or four risk factors, respectively (no patients had five or six risk factors present). The bias-adjusted area under the receiver-operator characteristic curve for the number of risk factors predicting rebleeding was 0.69. We have identified six easily remembered risk factors, which, when summed, predict recurrent hemorrhage following endoscopic therapy for non-variceal upper gastrointestinal hemorrhage.


Back pain "red flags": which are most predictive of serious pathology in the Emergency Department?
To determine the frequency of red flag signs and symptoms in patients presenting with back pain to the Emergency Department (ED) and association with serious pathologies and investigations performed. This retrospective observational study evaluated consecutive patients presenting with back pain to a Melbourne ED over a 14-month period. Data regarding red flags, patient characteristics, ED-initiated investigations, and diagnoses were extracted from medical records. Prevalence of each red flag and sensitivity, specificity, and likelihood ratios for diagnosing serious spinal or non-spinal pathology were calculated. Analysis was undertaken on 1000 eligible participants with back pain. 69% had red flags. Participants were categorised into diagnostic groups: musculoskeletal (80.6%), serious spinal (3.3%), and serious non-spinal (14.6%) pathologies. A number of red flags had positive likelihood ratios (LR) > 5, indicating a higher probability of serious pathology (spinal/non-spinal) including fever (LR + 68.8), tuberculosis history (LR + 13.8), known nephrolithiasis/abdominal aortic aneurysm (LR + 10.2), unexplained weight-loss (LR + 9.2), writhing in pain (LR + 6.9), urinary symptoms (LR + 5.4), and flank pain (LR + 5.2). Red flags with positive LR > 5 indicating a higher probability of serious spinal pathology were saddle anaesthesia (LR + 11.0), tuberculosis history (LR + 9.8), intravenous drug-use (LR + 6.9), acute-onset urinary retention (LR + 6.4), and anal tone loss (LR + 6.3). The majority of this study cohort had back pain of benign cause. Some red flags were associated with greater risk of serious pathology, others were not. Further evidence regarding red flags and their association with serious pathology is required, to better inform clinical guidelines.


LXRalpha functions as a cAMP-responsive transcriptional regulator of gene expression.
LXRalpha is a member of a nuclear receptor superfamily that regulates transcription. LXRalpha forms a heterodimer with RXRalpha, another member of this family, to regulate the expression of cholesterol 7alpha-hydroxylase by means of binding to the DR4-type cis-element. Here, we describe a function for LXRalpha as a cAMP-responsive regulator of renin and c-myc gene transcriptions by the interaction with a specific cis-acting DNA element, CNRE (an overlapping cAMP response element and a negative response element). Our previous studies showed that renin gene expression is regulated by cAMP, at least partly, through the CNRE sequence in its 5'-flanking region. This sequence is also found in c-myc and several other genes. Based on our cloning results using the yeast one-hybrid system, we discovered that the mouse homologue of human LXRalpha binds to the CNRE and demonstrated that it binds as a monomer. To define the function of LXRalpha on gene expression, we transfected the renin-producing renal As4.1 cells with LXRalpha expression plasmid. Overexpression of LXRalpha in As4.1 cells confers cAMP inducibility to reporter constructs containing the renin CNRE. After stable transfection of LXRalpha, As4.1 cells show a cAMP-inducible up-regulation of renin mRNA expression. In parallel experiments, we demonstrated that LXRalpha can also bind to the homologous CNRE in the c-myc promoter. cAMP promotes transcription through c-myc/CNRE:LXRalpha interaction in LXRalpha transiently transfected cells and increases c-myc mRNA expression in stably transfected cells. Identification of LXRalpha as a cAMP-responsive nuclear modulator of renin and c-myc expression not only has cardiovascular significance but may have generalized implication in the regulation of gene transcription.


Pathways to Preventing Substance Use Among Youth in Foster Care.
Substance use problems are highly prevalent among youth in foster care. Such problems in adolescence have long-lasting implications for subsequent adjustment throughout adulthood and even across generations. Although several programs have demonstrated positive results in reducing substance use in at-risk youth, few studies have systemically examined how such programs work for foster youth and whether they are effective for both genders. This study examined the efficacy of KEEP SAFE, a family-based and skill-focused program designed to prevent substance use and other related health risking behaviors among youth in foster care. We hypothesized that improving the caregiver-youth relationship would lead to later reductions in youths' involvement with deviant peers, which subsequently would lead to less substance use, and that this mechanism would work comparably for both genders. A sample of 259 youth (154 girls, ages 11-17 years) in foster care and their caregivers participated in a randomized controlled trial and was followed for 18 months post-baseline. Results indicated that the intervention significantly reduced substance use in foster youth at 18 months post-baseline and that the intervention influenced substance use through two processes: youths' improved quality of relationships with caregivers at 6 months post-baseline and fewer associations with deviant peers at 12 months post-baseline. This suggests that these two processes may be fruitful immediate targets in substance use prevention programs for foster youth. We also found little gender differences in direct and mediating effects of the intervention, suggesting KEEP SAFE may be effective for both genders in foster care.


Case closed? Diverticulitis: epidemiology and fiber.
A major advance in understanding diverticular disease occurred decades ago with the epidemiologic association between fiber intake and the development of diverticular disease. This association has been well documented with investigations into the emergence of diverticular disease in underdeveloped countries where the disease had been virtually unknown before the adoption of a westernized diet, low in fiber. The high frequency of right-sided diverticular disease in Asian countries diverges from what is seen in the West. The physiologic effects of insoluble fiber has been well examined as well, increasing bulk and decreasing transit time, with a deficiency contributing to the high pressures implicated in the physiology which leads to diverticular disease. However, at most, 10% to 25% of individuals with diverticular disease will develop diverticulitis. Risk factors for symptomatic diverticular have been increasingly described in recent years with obesity and red meat intake being of particular importance, in addition to age. However, the known factors poorly identify those at increased risk and the predisposing pathophysiology is incompletely understood as well. Insoluble fiber, but not soluble fiber, has been viewed as the principal component which has been deficient in western diets and is the culprit which leads to the establishment of diverticular disease and in turn, diverticulitis. Soluble fiber and its effect on the intestinal flora is proposed as having significant influence on the development of diverticulitis. This understanding, if demonstrated, would have important implications for the primary and secondary prevention of diverticulitis.


Caribbean Bulimulus revisited: physical moves and molecular traces (Mollusca, Gastropoda, Bulimulidae).
Twenty-five samples of Bulimulus species are studied, partly from localities within their known distribution range, partly based on interceptions where the material originates from localities where the species seem to be recently introduced and non-native. Molecular study of cytochrome oxidase 1 (CO1) reveals the origin of some of these introductions, but is less conclusive for others. Four different methods for species delimitation were applied, which did not result in unambiguous species hypotheses. For a rapid identification of morphologically indistinct species, a more comprehensive database of sequences is needed.


Flyway-scale GPS tracking reveals migratory routes and key stopover and non-breeding locations of lesser yellowlegs.
Many populations of long-distance migrant shorebirds are declining rapidly. Since the 1970s, the lesser yellowlegs (Tringa flavipes) has experienced a pronounced reduction in abundance of ~63%. The potential causes of the species' decline are complex and interrelated. Understanding the timing of migration, seasonal routes, and important stopover and non-breeding locations used by this species will aid in directing conservation planning to address potential threats. During 2018-2022, we tracked 118 adult lesser yellowlegs using GPS satellite tags deployed on birds from five breeding and two migratory stopover locations spanning the boreal forest of North America from Alaska to Eastern Canada. Our objectives were to identify migratory routes, quantify migratory connectivity, and describe key stopover and non-breeding locations. We also evaluated predictors of southbound migratory departure date and migration distance. Individuals tagged in Alaska and Central Canada followed similar southbound migratory routes, stopping to refuel in the Prairie Pothole Region of North America, whereas birds tagged in Eastern Canada completed multi-day transoceanic flights covering distances of >4000 km across the Atlantic between North and South America. Upon reaching their non-breeding locations, lesser yellowlegs populations overlapped, resulting in weak migratory connectivity. Sex and population origin were significantly associated with the timing of migratory departure from breeding locations, and body mass at the time of GPS-tag deployment was the best predictor of southbound migratory distance. Our findings suggest that lesser yellowlegs travel long distances and traverse numerous political boundaries each year, and breeding location likely has the greatest influence on migratory routes and therefore the threats birds experience during migration. Further, the species' dependence on wetlands in agricultural landscapes during migration and the non-breeding period may make them vulnerable to threats related to agricultural practices, such as pesticide exposure.


A survey of GTP-binding proteins and other potential key regulators of exocytotic secretion in eosinophils. Apparent absence of rab3 and vesicle fusion protein homologues.
We set out to identify potential key regulators of exocytotic fusion in the eosinophil, in the knowledge that granule exocytosis can be stimulated in these cells by intracellular application of nonhydrolyzable analogues of guanosine triphosphate, with Ca2+ acting as a modulator of guanine nucleotide-dependent secretion. To screen for GTP-binding proteins, guinea pig eosinophils were purified from peritoneal washings and subjected to western blotting analysis using specific immune sera raised against recombinant proteins or consensus peptide sequences within proteins of interest. We found a number of heterotrimeric G proteins (G alpha i3, G alpha o, G alpha q11, G alpha s and G beta subunits) and members of the small GTP-binding proteins expressed in eosinophils. Two subtypes of G-protein alpha subunits (G alpha i1 and G alpha z) could not be detected. Separation of subcellular organelles from homogenized eosinophils by density gradient centrifugation revealed that all of the detected GTP-binding proteins were mainly expressed in fractions containing peak plasma membrane and Golgi marker enzyme activities, while G beta subunits were also detected in secretory granule fractions. However, isoforms of Rab3, a putative GTP-binding regulator of exocytotic fusion, were undetectable in eosinophils. Neither, with the exception of syntaxin-3, could we detect any of the proteins belonging to the proposed synaptic vesicle fusion complex (SNAP-25; synaptobrevin (VAMP) and its non-neuronal homologue, cellubrevin; synaptophysin; synaptotagmin). The results from this study, based on western blotting, suggest that eosinophils express a different class of exocytotic fusion complex proteins from those found in neuronal tissues, although a number of potential candidates fulfilling the role of GE were identified in this important inflammatory cell.


Iris lymphoma-a systematic guide for diagnosis and treatment.
Iris lymphomas are rare malignant neoplasms arising either as primary tumors in the iris or as secondary tumors involving the iris. We summarize previously published data and make recommendations for work-up strategies for cases of suspected iris lymphoma. Our objective is to provide a structured overview of the typical clinical symptoms and signs, the pathologic, ophthalmic, as well as hematologic work-up for diagnosis, treatment, and follow-up of iris lymphomas and offer a flowchart on how to diagnose and treat these tumors.


A sampling framework for incorporating quantitative mass spectrometry data in protein interaction analysis.
Comprehensive protein-protein interaction (PPI) maps are a powerful resource for uncovering the molecular basis of genetic interactions and providing mechanistic insights. Over the past decade, high-throughput experimental techniques have been developed to generate PPI maps at proteome scale, first using yeast two-hybrid approaches and more recently via affinity purification combined with mass spectrometry (AP-MS). Unfortunately, data from both protocols are prone to both high false positive and false negative rates. To address these issues, many methods have been developed to post-process raw PPI data. However, with few exceptions, these methods only analyze binary experimental data (in which each potential interaction tested is deemed either observed or unobserved), neglecting quantitative information available from AP-MS such as spectral counts. We propose a novel method for incorporating quantitative information from AP-MS data into existing PPI inference methods that analyze binary interaction data. Our approach introduces a probabilistic framework that models the statistical noise inherent in observations of co-purifications. Using a sampling-based approach, we model the uncertainty of interactions with low spectral counts by generating an ensemble of possible alternative experimental outcomes. We then apply the existing method of choice to each alternative outcome and aggregate results over the ensemble. We validate our approach on three recent AP-MS data sets and demonstrate performance comparable to or better than state-of-the-art methods. Additionally, we provide an in-depth discussion comparing the theoretical bases of existing approaches and identify common aspects that may be key to their performance. Our sampling framework extends the existing body of work on PPI analysis using binary interaction data to apply to the richer quantitative data now commonly available through AP-MS assays. This framework is quite general, and many enhancements are likely possible. Fruitful future directions may include investigating more sophisticated schemes for converting spectral counts to probabilities and applying the framework to direct protein complex prediction methods.


A Novel Paradigm for Surgical Skills Training and Assessment of Competency.
Sustainment of comprehensive procedural skills in trauma surgery is a particular problem for surgeons in rural, global, and combat settings. Trauma care often requires open surgical procedures for low-frequency/high-risk injuries at a time when open surgical experience is declining in general and trauma surgery training. To determine whether general surgeons participating in a 2-day standardized trauma skills course demonstrate measurable improvement in accuracy and independent performance of specific trauma skills. General surgeons in active surgical practice were enrolled from a simulation center with anatomic laboratory from October 2019 to October 2020. Differences in pretraining/training and posttraining performance outcomes were examined using (1) pretraining/posttraining surveys, (2) pretraining/posttraining knowledge assessment, and (3) training/posttraining faculty assessment. Analysis took place in November 2020. A 2-day standardized, immersive, cadaver-based skills course, developed with best practices in instructional design, that teaches and assesses 24 trauma surgical procedures was used. Trauma surgery capability, as measured by confidence, knowledge, abilities, and independent performance of specific trauma surgical procedures; 3-month posttraining skill transfer. The study cohort included 65 active-duty general surgeons, of which 16 (25%) were women and 49 (75%) were men. The mean (SD) age was 38.5 (4.2) years. Before and during training, 1 of 65 participants (1%) were able to accurately perform all 24 procedures without guidance. After course training, 64 participants (99%) met the benchmark performance requirements for the 24 trauma procedures, and 51 (78%) were able to perform them without guidance. Procedural confidence and knowledge increased significantly from before to after the course. At 3 months after training, 37 participants (56%) reported skill transfer to trauma or other procedures. In this study, direct measurement of procedural performance following standardized training demonstrated significant improvement in skill performance in a broad array of trauma procedures. This model may be useful for assessment of procedural competence in other specialties.


A pan-cancer analysis of molecular characteristics and oncogenic role of gasdermins.
The gasdermins (GSDMs) family is proposed to be pore-forming effector proteins that cause cell membrane permeabilization and pyroptosis. Despite our increasing knowledge of GSDMD, GSDME and GSDMB, the biological functions and the regulation of GSDM expression and activation remain elusive for most GSDMs. In this study, we analyzed the molecular characteristics and oncogenic role of GSDM family genes systematically. TCGA, CCLE, cBioPortal, GEPIA, CellMiner and BioGRID databases were utilized in this study. Immunohistochemical analysis and a series of in vitro experiments were conducted. We found that, in cancer, GSDM genes and their expressions extensively changed, which were associated with patient survival. The expression of GSDMs was widely associated with cancer-related pathways, drug resistance, immune subtypes, tumor microenvironment and cancer cell stemness. However, an intra- and inter-cancer heterogeneity was discovered regarding the corresponding GSDM gene. We found that GSDMA and GSDMB regulated drug resistance to the opposite direction of GSDME. In colorectal cancer, GSDME might be a positive regulator in cell invasion and metastasis through cell migration and angiogenesis, while GSDMA, GSDMB and GSDMD might be a negatively regulator of cell migration. GSDM family genes might play important roles in cancer other than pyroptosis. We suggest more efforts be made to investigate the GSDM family and each GSDM gene be studied as an entity in each type of cancer.


Melatonin improves sleep quality of patients with chronic schizophrenia.
Accumulating evidence indicates decreased melatonin levels in patients with schizophrenia. Insomnia, mainly difficulty in falling asleep at night, is commonly reported in this population. Association of insomnia with low or abnormal melatonin rhythms has been repeatedly documented. Melatonin is an endogenous sleep promoter in humans. We hypothesized that insomnia in patients with schizophrenia may be partially due to diminished melatonin output. In this study, we measured melatonin output in patients with chronic schizophrenia and assessed the effects of melatonin replacement on their sleep quality. In a randomized, double-blind, cross-over, clinically based trial, 19 patients with DSM-IV schizophrenia who were treated with the normal treatment regimen were given melatonin (2 mg, controlled release) or placebo for 2 treatment periods of 3 weeks each with 1 week washout between treatment periods (7 weeks total). For measuring endogenous melatonin production, urine was collected from each patient every 3 hours between 9:00 p.m. and 9:00 a.m. Actigraphy was performed for 3 consecutive nights at the end of each period. Activity- and rest-derived sleep parameters were compared for the whole population with treatment arm as the intervening variable. A separate analysis was performed for patients subgrouped into high versus low sleep efficiency. All patients had low melatonin output. Melatonin replacement significantly improved rest-derived sleep efficiency compared with placebo (83.5% vs. 78.2%, p = .038) in this population. Improvement of sleep efficiency was significantly greater (p < .0014) in low-efficiency (80% vs. 67%) than high-efficiency sleepers (88% vs. 90%). In addition, during melatonin therapy, tendencies toward shortened sleep latency (by 40 minutes, p < .056) and increased sleep duration (by 45 minutes, p < .078) were observed in low- but not high-efficiency sleepers. Melatonin improves sleep efficiency in patients with schizophrenia whose sleep quality is low.


The effect of time to antifungal therapy on mortality in Candidemia associated septic shock.
The timely administration of appropriate antifungal therapy for Candida bloodstream infections (CBSI) improves clinical outcomes. However, little data exist on the effect of antifungal therapy in patients with septic shock and candidemia. We describe antifungal treatment of patients with septic shock due to CBSI and its impact on in-hospital mortality. We retrospectively reviewed medical records of hospitalized patients identified with at least one positive blood culture for Candida between January 2003 and June 2007. All septic shock patients received vasopressor therapy and had candidemia within 72 hours of refractory shock. Data collected included demographics, comorbidities, antibiotic exposure, in-hospital mortality, and intensive care-related factors. Acute Physiology and Chronic Health Evaluation II scores were calculated. Time to antifungal therapy was defined as the interval between time of collection of the first positive Candida blood culture and the time when appropriate antifungal therapy was initiated. Univariate and multivariate analyses were performed to identify variables associated with in-patient mortality. Classification and regression tree analysis was used to identify the mortality breakpoint between early and late antifungal therapy. Septic shock developed in 23% (31 of 135) patients with CBSI. In-hospital mortality was 68%. Nonalbicans Candida spp. accounted for 48% of blood isolates. Appropriate antifungal therapy was administered to 24 patients; 15 (63%) of these patients died. Classification and regression tree analysis revealed that patients who received appropriate antifungal therapy within 15 hours of collecting the first positive Candida blood culture had improved survival (P = 0.03). Early, appropriate antifungal therapy improves survival among patients with septic shock due to CBSI.


Alleviation of Cadmium Toxicity in Thai Rice Cultivar (PSL2) Using Biofertilizer Containing Indigenous Cadmium-Resistant Microbial Consortia.
Biofertilizer as an amendment has growing awareness. Little attention has been paid to bioremediation potential of indigenous heavy-metal-resistant microbes, especially when isolated from long-term polluted soil, as a bioinoculant in biofertilizers. Biofertilizers are a type of versatile nutrient provider and soil conditioner that is cost-competitive and highly efficient with nondisruptive detoxifying capability. Herein, we investigated the effect of biofertilizers containing indigenous cadmium (Cd)-resistant microbial consortia on rice growth and physiological response. The Thai rice cultivar PSL2 (Oryza sativa L.) was grown in Cd-enriched soils amended with 3% biofertilizer. The composition of the biofertilizers' bacterial community at different taxonomic levels was explored using 16S rRNA gene Illumina MiSeq sequencing. Upon Cd stress, the test biofertilizer had maximum mitigating effects as shown by modulating photosynthetic pigment, MDA and proline content and enzymatic antioxidants, thereby allowing increased shoot and root biomass (46% and 53%, respectively) and reduced grain Cd content, as compared to the control. These phenomena might be attributed to increased soil pH and organic matter, as well as enriched beneficial detoxifiers, i.e., Bacteroidetes, Firmicutes and Proteobacteria, in the biofertilizers. The test biofertilizer was effective in alleviating Cd stress by improving soil biophysicochemical traits to limit Cd bioavailability, along with adjusting physiological traits such as antioxidative defense. This study first demonstrated that incorporating biofertilizer derived from indigenous Cd-resistant microbes could restrict Cd contents and consequently enhance plant growth and tolerance in polluted soil.


Child-Pugh Classification: Time to Abandon?
The Child-Pugh classification is one of the commonest and oldest bedside tools utilized in estimating prognosis in patients with cirrhosis. However, its usage as a risk prediction tool or indeed a decision-making tool should be revisited. In this review, we discuss some inherent issues with the Child-Pugh classification and present a few contexts in which the current usage of Child-Pugh warrants reassessment, elaborating on its utility in acute variceal bleeding, specifically its role in decision-making on early transjugular intrahepatic portosystemic shunt, as well as its use in the context of hepatocellular carcinoma and drug development and dose adjustment.


Effectiveness of adulticide and larvicide in controlling high densities of Aedes aegypti in urban environments.
Current management and control of Aedes aegypti populations in urban areas are based on the spraying of insecticides. Here, we evaluated the effectiveness of spraying larvicide (Bacillus thuringiensis israelensis) using a truck-mounted Buffalo Turbine and adulticide (Deltamethrin) using a Grizzly ULV Sprayer in an urban area with high densities of Ae. aegypti and many cryptic and difficult to reach aquatic breeding habitats. Experiments were conducted in a tire shop located in Miami-Dade County, Florida with approximately 100,000 used airplane tires. Insecticide interventions were performed after a baseline survey consisting of 3 weeks of collections, followed by two insecticide interventions: (i) application of the adulticide followed by the application of larvicide on the subsequent week; and (ii) application of both adulticide and larvicide on two consecutive weeks. The first insecticide intervention resulted in a non-significant decrease in the relative abundance of Ae. aegypti. On the other hand, the second insecticide intervention significantly reduced the Ae. aegypti relative abundance (P < 0.002). Our results demonstrated that the combined insecticide interventions on two consecutive weeks significantly reduced the relative abundance of Ae. aegypti. This result indicated that the larvicide was successfully propelled reaching cryptical and difficult to reach aquatic habitats. However, even though the number of mosquitoes was greatly reduced, it was still greatly above the 10-mosquito threshold by trap night used by the Miami-Dade Mosquito Control Division to deploy an inspector to survey the area. Considering the lack of new and effective mosquito control tools, efficient and mobile insecticide propellers such as Buffalo Turbine can be of great help to manage mosquito populations in urban areas.


Distal Electroacupuncture at the LI4 Acupoint Reduces CFA-Induced Inflammatory Pain via the Brain TRPV1 Signaling Pathway.
There is accumulating evidence supporting electroacupuncture's (EA) therapeutic effects. In mice, local EA reliably attenuates inflammatory pain and increases the transient receptor potential cation channel, subfamily V, member 1 (TRPV1). However, the effect of distal acupoint EA on pain control has rarely been studied. We used a mouse model to investigate the analgesic effect of distal EA by measuring TRPV1 expression in the brain. Complete Freund's adjuvant (CFA) was injected into mice's hind paws to induce inflammatory pain. The EA-treated group received EA at the LI4 acupoint on the bilateral forefeet on the second and the third days, whereas the control group underwent sham manipulation. Mechanical and thermal pain behavior tests showed that the EA-treated group experienced inflammatory pain alleviation immediately after EA, which did not occur in the sham group. Additionally, following CFA injection, the expression of TRPV1-associated molecules such as phosphorylated protein kinase A (pPKA), extracelluar signal-regulated kinase (pERK), and cAMP-response-element-binding protein (pCREB) increased in the prefrontal cortex (PFC) and the hypothalamus but decreased in the periaqueductal gray (PAG) area. These changes were significantly attenuated by EA but not sham EA. Our results show an analgesic effect of distal EA, which is based on the traditional Chinese medicine theory. The mechanism underlying this analgesic effect involves TRPV1 in the PFC, the hypothalamus, and the PAG. These novel findings are relevant for the evaluation and the treatment of clinical inflammatory pain syndrome.


Dietary cholesterol oxidation products accelerate plaque destabilization and rupture associated with monocyte infiltration/activation via the MCP-1-CCR2 pathway in mouse brachiocephalic arteries: therapeutic effects of ezetimibe.
No prior studies have investigated the effects of dietary cholesterol oxidation products (oxysterols) on atherosclerotic plaque destabilization and rupture. We used an atherosclerotic mouse model with histological features similar to those seen in ruptured human plaques to test the hypothesis that (1) dietary oxysterols accelerate plaque destabilization and rupture and (2) a NPC1L1 inhibitor, ezetimibe, has therapeutic effects on these processes. Advanced atherosclerotic plaques were examined in innominate arteries of ApoE(-/-) mice that were fed either a regular high-fat diet (HFD) or HFD containing oxysterols (oxysterol-HFD; 6.8% of added cholesterol was oxidized) and infused with angiotensin II. Compared with HFD, oxysterol-HFD did not affect plasma lipid levels but did accelerate plaque destabilization and rupture, which was associated with increased monocyte infiltration/activation, monocyte chemoattractant protein-1 (MCP-1) expression, and matrix metalloproteinase (MMP) activity. Dietary oxysterol-induced plaque destabilization and rupture were blunted in ApoE(-/-) CCR2(-/-) mice. Oral treatment with ezetimibe, significantly decreased plasma lipid levels and prevented the acceleration of plaque destabilization and rupture induced by dietary oxysterol. These data indicate a primary role for monocyte-mediated inflammation via the MCP-1-CCR2 pathway and the resultant increase in MMP activity in plaque destabilization and rupture induced by dietary oxysterols in ApoE(-/-) mice. These data also provide a mechanism by which dietary oxysterols are connected with the pathogenesis of plaque destabilization and rupture. These data suggest that inhibition of the absorption of oxysterols by ezetimibe may be useful for the treatment of high-risk patients with high oxysterol intake.


Integrative proteomics reveals principles of dynamic phosphosignaling networks in human erythropoiesis.
Human erythropoiesis is an exquisitely controlled multistep developmental process, and its dysregulation leads to numerous human diseases. Transcriptome and epigenome studies provided insights into system-wide regulation, but we currently lack a global mechanistic view on the dynamics of proteome and post-translational regulation coordinating erythroid maturation. We established a mass spectrometry (MS)-based proteomics workflow to quantify and dynamically track 7,400 proteins and 27,000 phosphorylation sites of five distinct maturation stages of in vitro reconstituted erythropoiesis of CD34+ HSPCs. Our data reveal developmental regulation through drastic proteome remodeling across stages of erythroid maturation encompassing most protein classes. This includes various orchestrated changes in solute carriers indicating adjustments to altered metabolic requirements. To define the distinct proteome of each maturation stage, we developed a computational deconvolution approach which revealed stage-specific marker proteins. The dynamic phosphoproteomes combined with a kinome-targeted CRISPR/Cas9 screen uncovered coordinated networks of erythropoietic kinases and pinpointed downregulation of c-Kit/MAPK signaling axis as key driver of maturation. Our system-wide view establishes the functional dynamic of complex phosphosignaling networks and regulation through proteome remodeling in erythropoiesis.


A successful approach to minimizing attrition in racial/ethnic minority, low-income populations.
Recruiting and retaining minority participants in clinical trials continue to be major challenges. Although multiple studies document lower minority trial enrollment, much less is known about effective minority retention strategies. Our objectives were to evaluate an innovative approach to high RCT retention of minority children, and identify child/caregiver characteristics predicting attrition. The Kids' HELP trial examined the effects of Parent Mentors on insuring uninsured minority children. We tested a retention strategic framework consisting of: 1) optimizing cultural/linguistic competency; 2) staff training on participant relationships and trust; 3) comprehensive participant contact information; 4) an electronic tracking database; 5) reminders for upcoming outcomes-assessment appointments; 6) frequent, sustained contact attempts for non-respondents; 7) financial incentives; 8) individualized rapid-cycle quality-improvement approaches to non-respondents; 9) reinforcing study importance; and 10) home assessment visits. We compared attrition in Kids' HELP vs. two previous RCTs in similar populations, and conducted bivariate and multivariable analyses of factors associated with Kids' HELP attrition. Attrition in Kids' HELP was lower than in two similar RCTs, at 10.9% vs. 37% and 40% (P <0.001). After multivariable adjustment, missing the first outcomes follow-up assessment was the only factor significantly associated with attrition (relative risk=1.5; 95% confidence interval, 1.1-2.0). A retention strategic framework was successful in minimizing attrition in minority, low-income children. Participants missing first assessment appointments were at highest risk of subsequent attrition. These findings suggest that deploying this framework may help RCT retention of low-income minority children, particularly those at the highest risk of subsequent attrition.


Irreversible electroporation and adjuvant chemoradiotherapy for locally advanced pancreatic carcinoma.
The safety and efficacy of irreversible electroporation (IRE) for locally advanced pancreatic carcinoma (LAPC) are well established. However, whether adjuvant chemoradiotherapy after IRE increases, the survival rate remains unknown. Therefore, this study evaluated the effect of chemoradiotherapy combined with IRE in patients with LAPC. We retrospectively analyzed 42 patients with LAPC between July 2015 and December 2016 at PLA General Hospital treated with IRE or IRE combined with radiation and/or chemotherapy. These patients were divided into the IRE group and the combined-therapy group. All patients underwent computed tomography (CT), magnetic resonance imaging, and positron-emission tomography-CT and no signs of metastases were found. The prognosis of these patients was observed. The times after operation and after diagnosis in the combined-therapy group (304.20 ± 118.54) and (334.40 ± 114.07) days, respectively, were better those than in the IRE group (214.36 ± 95.68) and (244.68 ± 110.61) days, respectively. Moreover, patients in the combined-therapy group had a significantly better survival rate than the IRE group (80 vs. 45.45%, P < 0.05). IRE combined with radiotherapy or chemotherapy was superior to IRE alone for the treatment of LAPC, as it prolonged the survival time and improved the survival rate, making it worthy of wide dissemination and clinical application.


Evaluation of the intracranial dural sinuses with a 3D contrast-enhanced MP-RAGE sequence: prospective comparison with 2D-TOF MR venography and digital subtraction angiography.
The diagnosis of dural sinus thrombosis is often difficult because of its variable and nonspecific clinical presentation and the overlapping signal intensities of thrombosis and venous flow on conventional MR images and MR venograms. We compared 3D contrast-enhanced magnetization-prepared rapid gradient-echo (MP-RAGE) sequences with 2D time-of-flight (TOF) MR venography, digital subtraction angiography (DSA), and conventional spin-echo (SE) MR imaging for the assessment of normal and abnormal dural sinuses. In a phantom study, a plastic tube with pulsating flow was used to simulate the intracranial dural sinus. With 3D MP-RAGE, a variety of flow velocities, contrast material concentrations, and angulations between the phantom flow tube and the plane of acquisition were tested to measure their relationship to signal-to-noise ratio (SNR). In a clinical study, 35 patients, including 18 with suspected dural sinus thrombosis, were studied with both MR imaging and DSA. Receiver operating characteristic (ROC) analysis was performed in a blinded fashion using DSA as the reference standard. With the phantom, the SNR of flow increased with increasing contrast concentration, but was not affected by the angle between the tube and scan slab. There was no relationship between SNR and velocity when the contrast concentration was 1.0 mmol/L or greater. In the clinical study, dural sinus thrombosis as well as the normal anatomy of the dural sinuses were seen better with 3D contrast-enhanced MP-RAGE than with 2D-TOF MR venography. Three-dimensional contrast-enhanced MP-RAGE showed the highest diagnostic confidence on ROC curves in the diagnosis of thrombosis. Three-dimensional contrast-enhanced MP-RAGE is superior to 2D-TOF MR venography and conventional SE MR imaging in the depiction of normal venous structures and the diagnosis of dural sinus thrombosis, and is a potential alternative to DSA.


Prospective study of neurological responses to treatment with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher's disease.
We prospectively evaluated the clinical and biochemical responses to enzyme-replacement therapy (ERT) with macrophage-targeted glucocerebrosidase (Ceredase) infusions in 5 patients (age, 3.5-8.5 years) with type 3 Gaucher's disease. The patients were followed for up to 5 years. Enzyme dosage ranged from 120 to 480 U/kg of body weight/month. Systemic manifestations of the disease regressed in all patients. Neurological deficits remained stable in 3 patients and slightly improved in 1. One patient developed myoclonic encephalopathy. Cognitive deterioration occurred in 1 patient and electroencephalographic deterioration in 2. Sequential cerebrospinal fluid (CSF) samples were obtained during the first 3 years of treatment in 3 patients and were analyzed for biochemical markers of disease burden. Glucocerebroside and psychosine levels were not elevated in these specimens, whereas chitotriosidase and quinolinic acid were elevated in 2 patients. Progressive decrease in the CSF levels of these latter macrophage markers during 3 years of treatment implies a decreased number of Gaucher cells in the cerebral perivascular space. Similar changes were not observed in the patient who had a poor neurological outcome. In conclusion, ERT reverses systemic manifestations of type 3 Gaucher's disease and appears to reduce the burden of Gaucher cells in the brain-CSF compartment in some patients.


Long sleep duration and childhood overweight/obesity and body fat.
To assess the association between short sleep duration and overweight/obesity and body fat (BF) and to identify correlates of short sleep duration in a sample of Portuguese children. A cross-sectional study of children 7-9 years (n = 4511) was performed between October 2002 and June 2003. Weight, height, and skinfolds were measured, and parents filled out a questionnaire about family characteristics as well as sleep duration. The prevalence of overweight/obesity and BF (%) both decreased by long sleep duration. After adjusted for confounders, the odds ratio (OR) for overweight/obesity and sleep duration were as follows: reference >11 h/d; 10-11 h/d, OR: 1.3; confidence interval (CI):1.26, 1.33; 9-10 h/d, OR: 1.16; CI: 1.13, 1.19; and <9 h, OR: 3.22; CI: 3.11, 3.32. Children whose parents had a low educational level slept less time during each night than children whose parents had a higher educational level; children who spent more time watching television slept less time than those who watched less television, and those children engaged in physical activity slept more time each night than sedentary children. Our results showed an inverse relationship between long sleep duration and overweight/obesity prevalence as well as with body fat, and these findings are important because sleep duration is a potentially modifiable risk factor that could be important to consider in the prevention and treatment of childhood obesity.


Management of ectopically erupting first permanent molars.
A simple method of treating these teeth is described. The authors describe the use of orthodontic brackets, .017 twist wire, and compressed open coil springs. Correction is accomplished in six to eight weeks with minimal adjustments required.


Substitutions in bacteriophage T4 AsiA and Escherichia coli sigma(70) that suppress T4 motA activation mutations.
Bacteriophage T4 middle-mode transcription requires two phage-encoded proteins, the MotA transcription factor and AsiA coactivator, along with Escherichia coli RNA polymerase holoenzyme containing the sigma(70) subunit. A motA positive control (pc) mutant, motA-pc1, was used to select for suppressor mutations that alter other proteins in the transcription complex. Separate genetic selections isolated two AsiA mutants (S22F and Q51E) and five sigma(70) mutants (Y571C, Y571H, D570N, L595P, and S604P). All seven suppressor mutants gave partial suppressor phenotypes in vivo as judged by plaque morphology and burst size measurements. The S22F mutant AsiA protein and glutathione S-transferase fusions of the five mutant sigma(70) proteins were purified. All of these mutant proteins allowed normal levels of in vitro transcription when tested with wild-type MotA protein, but they failed to suppress the mutant MotA-pc1 protein in the same assay. The sigma(70) substitutions affected the 4.2 region, which binds the -35 sequence of E. coli promoters. In the presence of E. coli RNA polymerase without T4 proteins, the L595P and S604P substitutions greatly decreased transcription from standard E. coli promoters. This defect could not be explained solely by a disruption in -35 recognition since similar results were obtained with extended -10 promoters. The generalized transcriptional defect of these two mutants correlated with a defect in binding to core RNA polymerase, as judged by immunoprecipitation analysis. The L595P mutant, which was the most defective for in vitro transcription, failed to support E. coli growth.


The uniformity of liver perfusion as measured by krypton-85 clearance.
The uniformity of regional liver perfusion was studied in eight anaesthetised dogs by measuring the clearance of 85Kr with three beta detectors, and the results were compared with independent measurements of mean perfusion by electromagnetic flowmetry. The intra-hepatic flow distribution was found to be heterogeneous, with a coefficient of variation between locations which averaged 17%. The pattern of flow varied from liver to liver, and there was no consistent tendency for any one of a limited number of locations to be better or less well perfused than any other. Discrepancies between 85Kr clearance and flowmeter measurements were of a similar magnitude to inter-regional variations in flow, and there was no evidence of a systematic difference between the two measurement techniques. Individual 85Kr clearance measurements can misrepresent the perfusion of the liver as a whole, and averaging several measurements performed in different locations is likely to yield a better estimate of mean flow.


High-Quality Chest Compression for Cardiopulmonary Resuscitation Using Newly-Designed Automatic Device.
High-quality chest compression during cardiopulmonary resuscitation (CPR) can remarkably improve survival rate and reduce the risk of secondary injury. In this study, a newly-designed automatic chest compression device was applied on an animal model and the effects of chest compression were examined in comparison of manual compression and machine compression by a commercialized device. Three pigs (weight:30±2 kg) were used for the experiment. A LUCAS2 CPR machine and the newly-designed CPR device were used for automatic compression treatment. Compression pressure and chest displacement were collected in the process of CPR. Regarding the statistical distribution of compression depths, the new CPR device showed a mean of the depths at 1.64 inches, which was greater than that of manual (mean = 1.21 inches) and of LUCAS2 (mean = 1.18 inches). In addition, the new CPR device showed a standard deviation (SD) of compression depths at 0.07 inches, which was lower than that of manual (SD = 0.15 inches) and of LUCAS2 (SD = 0.25 inches). These results suggested that the new CPR device performed higher compression depths with lower compression variability, indicating enforced compression and better stability. This study provided a preliminarily outcomes validating the new CPR device, which may play a role in high-quality chest compression for the first aid in emergency.Clinical Relevance- This study established an animal model to validate a newly-designed automatic device for CPR. Comparing with manual chest compression and automatic compression using LUCAS2, the new device showed greater compression depths and better stability, which may provide more effective CPR treatment for clinical usage.


Linking quality-of-life measures using the International Classification of Functioning, Disability and Health and the International Classification of Functioning, Disability and Health-Children and Youth Version in chronic health conditions: the example of young people with hemophilia.
This study aimed to measure the health and functioning of children with hemophilia in Europe using the International Classification of Functioning, Disability and Health (ICF) and the International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY) as a frame of reference and items from health-related quality-of-life instruments as a measurement tool within a European data set. Based on the results of linkage of items from the hemophilia-specific health-related quality-of-life questionnaire for children and adolescents to ICF/ICF-CY, the categories most relevant for the description of health and functioning of children with hemophilia were identified for each domain of the ICF/ICF-CY. Using data from the European Study of Clinical, Health, Economic, and Quality-of-Life Outcomes of Hemophilia treatment on 446 children, the frequency of impairments in body structures and body functions, restrictions in activities and participation, and barriers in contextual factors were calculated. In general, the frequency of impairments, restrictions, and barriers was low in the studied population of children with hemophilia. However, the level of restriction as well as barriers was higher than the level of impairments. Older children, children receiving on-demand treatment, and children with severe hemophilia tended to have more problems compared with younger children, children receiving prophylaxis treatment, and children with mild to moderate hemophilia. Using items from quality-of-life instruments with the ICF-CY as a frame of reference proved to be a useful approach for the assessment of health and functioning in children with hemophilia.


Functional divergence of a heterochromatin-binding protein during stickleback speciation.
Intragenomic conflict, the conflict of interest between different genomic regions within an individual, is proposed as a mechanism driving both the rapid evolution of heterochromatin-related proteins and the establishment of intrinsic genomic incompatibility between species. Although molecular studies of laboratory model organisms have demonstrated the link between heterochromatin evolution and hybrid abnormalities, we know little about their link in natural systems. Previously, we showed that F1 hybrids between the Japan Sea stickleback and the Pacific Ocean stickleback show hybrid male sterility and found a region responsible for hybrid male sterility on the X chromosome, but did not identify any candidate genes. In this study, we first screened for genes rapidly evolving under positive selection during the speciation of Japanese sticklebacks to find genes possibly involved in intragenomic conflict. We found that the region responsible for hybrid male sterility contains a rapidly evolving gene encoding a heterochromatin-binding protein TRIM24B. We conducted biochemical experiments and showed that the binding affinity of TRIM24B to a heterochromatin mark found at centromeres and transposons, histone H4 lysine 20 trimethylation (H4K20me3), is reduced in the Japan Sea stickleback. In addition, mRNA expression levels of Trim24b were different between the Japan Sea and the Pacific Ocean testes. Further expression analysis of genes possibly in the TRIM24B-regulated pathway showed that some gypsy retrotransposons are overexpressed in the F1 hybrid testes. We, therefore, demonstrate that a heterochromatin-binding protein can evolve rapidly under positive selection and functionally diverge during stickleback speciation.


Dengue and dengue haemorrhagic fever: implications of host genetics.
Little is known of the role of human leucocyte antigen (HLA) alleles or non-HLA alleles in determining resistance, susceptibility or the severity of acute viral infections. Dengue fever (DF) and dengue haemorrhagic fever (DHF) are suitable models for immunogenetic studies, yet only superficial efforts have been made to study dengue disease to date. DF and DHF can be caused by both primary and secondary infection by any of the four serotypes of the dengue virus. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virus virulence. Variations in immune response, often associated with polymorphism in the human genome, can now be detected. Data on the influence of human genes in DF and DHF are discussed here in relation to (1) associations between HLA polymorphism and dengue disease susceptibility or resistance, (2) protective alleles influencing progression to severe disease, (3) alleles restricting CD4(+) and CD8(+) T lymphocytes, and (4) non-HLA genetic factors that may contribute to DHF evolution. Recent discoveries regarding genetic associations in other viral infections may provide clues to understanding the development of end-stage complications in dengue disease. The scanty positive data presented here indicate a need for detailed genetic studies in different ethnic groups in different countries during the acute phase of DF and DHF on a larger number of patients.


[Are new data collection systems needed to achieve public health and research goals for the prevention of suicide?].
Evaluation of suicide prevention programs, both on the local and national level, is a methodological challenge. In September 2000, France initiated a nation program for suicide prevention. But, as was noted in the Prémutan report and more recently the FNORS report, very few of the hundreds of preventive measures taken annually are evaluated. In addition to this assessment challenge, new data, particularly concerning the different phases of the suicide process, are needed to design new programs, define their objectives with precision, and assure their implementation. For example, if the objective is to improve prevention in men aged 25-54 years who suffer from a state of depression, alcohol abuse, impulsive personality disorders, and life events implicating loss, the necessary information is currently unavailable or sparse. The lack of data and research in this domain can be grouped into several categories: lack of proper definition and quantification of the objectives; insufficient study of the mechanisms by which prevention measures are effective: lack of monitoring tools providing information on the rate of implementation of planned actions. These arguments demonstrate the need for collecting new information to develop a dynamic prevention program. Such data collection should be synchronized, conducted by a wide range of actors, and concern multiple actions. Without a coherent information system, it is doubtful the current impetus for the prevention of suicide can be sustained.


Fasciitis necrotisans - duplicitas casuum.
Necrotizing fasciitis is a dangerous bacterial infectious disease that is not commonplace in Czech society. On the other hand, neither is it so rare that the majority of surgeons should not come across it occasionally. In the early stages, pathological changes in fascia, subcutaneous tissue and even skin may run an inconspicuous course. However, this can rapidly deteriorate into shock and sepsis which may lead to multi-organ failure and an imminent life-threatening condition. The fatality rate of necrotizing fasciitis among high-risk groups (e.g. diabetics, patients who are immuno-compromised, obese and/or elderly, malnourished, or with a history of drug use), is particularly steep, reaching as high as 73%. Treatment for this condition consists of early, radical surgical intervention in conjunction with targeted antibiotherapy. Complex resuscitative and intensive care, including rehabilitation, are standard components of post-surgical management. Use of hyperbaric oxygen therapy, if such an opportunity exists, is also recommended. Interdisciplinary collaboration is a vital prerequisite for successful treatment. This article describes two case-studies of necrotizing fasciitis that occurred in men of similar age during a three-year period. Both patients presented with very similar and complicated disease courses, and both were successfully treated by the same interdisciplinary team comprised of clinicians from various specialized departments. Key words: necrotizing fasciitis - radical necrectomy - antibiotherapy - hyperbaric oxygen therapy - complex resuscitative and intensive care.


The Association Between Race, Ethnicity and Sleep Quality and Duration: A National Health Interview Survey Study.
Inadequate sleep duration and poor sleep quality are associated with adverse cardiovascular outcomes. Using data from the National Health Interview Survey, we compared self-reported sleep duration and quality among different groups: Whites, Chinese, Asian Indian, Filipino, and Other Asians. Outcome included Sleep duration (≥7 and <7 hours) and sleep quality (coded as a binary variable). We included 155,203 participants. The overall prevalence of ≥7 hours of sleep was 69.5% and poor sleep quality was reported by 73.9%. Compared to Whites and Chinese, Filipinos, and Other Asians were less likely to get adequate sleep (≥7 hours). All 4 Asian groups were less likely to report poor sleep quality compared with White individuals, while Asian Indians reported poor sleep quality less frequently compared with Chinese individuals. There are significant differences in sleep duration and quality between White and Asian groups, as well as within Asian subgroups. Further studies with disaggregated Asian subgroup data are needed to formally study these disparities.


Implications of Corona Virus Disease-19 pandemic on cytopathology laboratory-Challenges and solutions in resource-limited settings.
Corona Virus Disease-19 (COVID-19) disease which is still showing peaks and plateau with emerging new mutational viral variants has led to the modification of working of hospitals and medical institutes. Cytopathology laboratories geared up with the changing situation to cope up with not only the COVID-19 patients but also patients of other diseases, particularly oncology patients. It was also important to adopt changes in the cytopathology residency program so as to cope up with the changing scenario. The present study was conducted to study the various measures adopted and the changes made in the cytopathology laboratory during COVID-19 infection in a resource-limited setting while catering to a large population of COVID-19-positive patients in the north Himalayan region of India. It was also intended to study the methods adopted for effective cytopathology residency training during corona times. The study was conducted from March 2020 to December 2021 in the cytopathology lab, and all the samples were analyzed and compared with the samples received in pre-corona times from March 2018 to December 2019. The different methods adopted during corona times for effective cytopathology residency training were also analyzed. The total number of samples received in the cytopathology laboratory in pre-corona times from March 2018 to December 2019 were 6822, and samples received from March 2020 to December 2021 were 6567 with decrease of 1.9% of cases. There was increase in 17.4% for the samples of the respiratory tract received in the lab with an increase in cases of infections including aspergillosis, mucormycosis, and tuberculosis. There was 10.3% increase in cytological diagnosis of malignant cases during corona times. Use of 90% alcohol for fixation rather than air drying of smears, avoiding of pneumatic tubes, judicious use of personal protective equipment (PPE) kits along with access to the digital cytology slide database were included in the changes made in the lab. There was a marginal decrease in cytopathological diagnosis during COVID-19 with substantial increase in the malignancy rate of 10.3% in cytological diagnosis of different organs. Diagnosis of mucormycosis, aspergillosis, and tuberculosis infections of respiratory tract cytology increased during this period. Judicious use of limited available resources led not only to smooth functioning of the cytopathology lab but also prevented any infection in the working health personals. Newer online resources were explored and modified for continuous training of the cytopathology residents. Emotional support with effective communication was the key to alleviate any psychological stress among all health professionals in the cytopathology laboratory.


Disrupted kisspeptin signaling in GnRH neurons leads to hypogonadotrophic hypogonadism.
Landmark studies have shown that mutations in kisspeptin and the kisspeptin receptor (Kiss1r) result in reproductive dysfunction in humans and genetically altered mouse models. However, because kisspeptin and its receptor are present in target cells of the central and peripheral reproductive axis, the precise location(s) for the pathogenic signal is unknown. The study described herein shows that the kisspeptin-Kiss1r signaling pathway in the GnRH neuron is singularly critical for both the onset of puberty as well as the attainment of normal reproductive function. In this study, we directly test the hypothesis that kisspeptin neurons regulate GnRH secretion through the activation of Kiss1r on the plasma membrane of GnRH neurons. A GnRH neuron-specific Kiss1r knockout mouse model (GKirKO) was generated, and reproductive development and phenotype were assessed. Both female and male GKirKO mice were infertile, having low serum LH and FSH levels. External abnormalities such as microphallus and decreased anogenital distance associated with failure of preputial gland separation were present in GKirKO males. A delay in pubertal onset and abnormal estrous cyclicity were observed in female GKirKO mice. Taken together, these data provide in vivo evidence that Kiss1r in GnRH neurons is critical for reproductive development and fertility.


Radiation from a homogeneous isothermal sphere.
The theory of electromagnetic fluctuations as developed by Rytov was used to calculate the radiant power as a function of frequency radiated from a homogeneous isothermal sphere. The formula obtained is valid for all radii, frequencies, and complex dielectric constants. It is also shown that the emission coefficient computed from this theory is precisely equal to the absorption coefficient computed from the Mie theory. The formula obtained is readily adaptable to numerical calculations, and results are presented for the case of a good conducting sphere with a wide range of size parameters.


Apoptosis and injuries of heavy ion beam and x-ray radiation on malignant melanoma cell.
This study aims to investigate the influence of high linear energy transfer (LET) heavy ion (12C6+) and low LET X-ray radiation on apoptosis and related proteins of malignant melanoma on tumor-bearing mice under the same physical dosage. C57BL/6 J mice were burdened by tumors and randomized into three groups. These mice received heavy ion (12C6+) and X-ray radiation under the same physical dosage, respectively; their weight and tumor volumes were measured every three days post-radiation. After 30 days, these mice were sacrificed. Then, median survival time was calculated and tumors on mice were proliferated. In addition, immunohistochemistry was carried out for apoptosis-related proteins to reflect the expression level. After tumor-bearing mice were radiated to heavy ion, median survival time improved and tumor volume significantly decreased in conjunction with the upregulated expression of pro-apoptosis factors, Bax and cytochrome C, and the downregulated expression of apoptosis-profilin (Bcl-2, Survivin) and proliferation-related proteins (proliferating cell nuclear antigen). The results indicated that radiation can promote the apoptosis of malignant melanoma cells and inhibit their proliferation. This case was more suitable for heavy ion (12C6+). High LET heavy ion (12C6+) radiation could significantly improve the killing ability for malignant melanoma cells by inducing apoptosis in tumor cells and inhibiting their proliferation. These results demonstrated that heavy ion (12C6+) presented special advantages in terms of treating malignant melanoma. Impact statement Malignant melanoma is a malignant skin tumor derived from melanin cells, which has a high malignant degree and high fatality rate. In this study, proliferating cell nuclear antigen (PCNA) can induce the apoptosis of malignant melanoma cells and inhibit its proliferation, and its induction effect on apoptosis is significantly higher than low LET X-ray; hence, it is expected to overcome its lower sensitivity to radiation. This study can provide theoretical basis for clinical trials, in which malignant melanoma is treated by heavy ion (12C6+), in order to accurately determine the clinical efficacy of heavy ion therapy. Clinical applications has revealed that local tumor control rate is high when heavy ion is used to treat malignant melanoma, indicating that heavy ion is an important direction in treating melanoma in the future.


Deciphering the 4 D's: cognitive decline, delirium, depression and dementia--a review.
The purpose of this paper is to assist advanced practice nurses to recognize, identify, and diagnose cognitive change in older adults. Optimal cognitive function is important for continued independence, and yet changes in cognition are frequently unrecognized among older adults. Cognitive change in older adults can be observed due to age-related cognitive decline, the development of acute confusion (delirium), depression, dementia and/or a combination of these. When the aetiological source for alterations in cognitive function is delirium or depression, the potential for reversibility mandates that the reason for the cognitive change be identified with steps taken to remedy the situation. Also, early recognition of dementia is an important factor in obtaining timely and appropriate care. These conditions can exist concurrently and may fluctuate making deciphering the reason for the cognitive change problematic. It is essential to understand how the 4 'D's' are expressed and to recognize the potential contributing factors to an observable change in cognitive function for diagnosis and treatment. Recommendations for obtaining a person's history are included.


Imaging Isomers on a Biological Surface: A Review.
Mass spectrometry imaging is an imaging technology that allows the localization and identification of molecules on (biological) sample surfaces. Obtaining the localization of a compound in tissue is of great value in biological research. Yet, the identification of compounds remains a challenge. Mass spectrometry alone, even with high-mass resolution, cannot always distinguish between the subtle structural differences of isomeric compounds. This review discusses recent advances in mass spectrometry imaging of lipids, steroid hormones, amino acids and proteins that allow imaging with isomeric resolution. These improvements in detailed identification can give new insights into the local biological activity of isomers.


Long-term irritable bowel syndrome symptom control with reintroduction of selected FODMAPs.
To investigate the long-term effect of dietary education on a low fermentable oligosaccharide, disaccharide and polyol (FODMAP) diet on irritable bowel syndrome (IBS) symptoms and quality of life (QoL). Participants with IBS (Rome III) were randomized to two groups. Group I commenced a low FODMAP diet at baseline. At three months, group II, so far a comparator group, crossed over to a low FODMAP diet while group I started re-challenging foods. All patients completed the IBS SSS (IBS symptom severity scoring system, 0-500 points increasing with severity), IBS QoL questionnaire (0-100 increasing with QoL), a FODMAP specific food frequency questionnaire and provided a stool sample at baseline, three and six months for microbiome analysis. Fifty participants were enrolled into group I (n = 23) or group II (n = 27). Participants in both groups were similar in baseline values but with more men in group I. There was a significantly lower IBS SSS (275.6 ± 63.6 to 128.8 ± 82.5 vs 246.8 ± 71.1 to 203.6 ± 70.1) (P < 0.0002) and increased QoL (68.5 ± 18.0 to 83 ± 13.4 vs 72.9 ± 12.8 to 73.3 ± 14.4) (P < 0.0001) in group I vs group II at 3 mo. The reduced IBS SSS was sustained at 6 mo in group I (160 ± 102) and replicated in group II (124 ± 76). Fiber intake decreased on the low FODMAP diet (33 ± 17 g/d to 21 ± 8 g/d) (P < 0.01) and after re-introducing FODMAP containing foods increased again to 27 ± 9 g/d. There was no change seen in the intestinal microbiome when participants adopted a low FODMAP diet. This study demonstrated that a reduction in FODMAPs improves symptoms in IBS and this improvement can be maintained while reintroducing FODMAPs.


Reversal of autism-like behaviors and metabolism in adult mice with single-dose antipurinergic therapy.
Autism spectrum disorders (ASDs) now affect 1-2% of the children born in the United States. Hundreds of genetic, metabolic and environmental factors are known to increase the risk of ASD. Similar factors are known to influence the risk of schizophrenia and bipolar disorder; however, a unifying mechanistic explanation has remained elusive. Here we used the maternal immune activation (MIA) mouse model of neurodevelopmental and neuropsychiatric disorders to study the effects of a single dose of the antipurinergic drug suramin on the behavior and metabolism of adult animals. We found that disturbances in social behavior, novelty preference and metabolism are not permanent but are treatable with antipurinergic therapy (APT) in this model of ASD and schizophrenia. A single dose of suramin (20 mg kg(-1) intraperitoneally (i.p.)) given to 6-month-old adults restored normal social behavior, novelty preference and metabolism. Comprehensive metabolomic analysis identified purine metabolism as the key regulatory pathway. Correction of purine metabolism normalized 17 of 18 metabolic pathways that were disturbed in the MIA model. Two days after treatment, the suramin concentration in the plasma and brainstem was 7.64 μM pmol μl(-1) (±0.50) and 5.15 pmol mg(-1) (±0.49), respectively. These data show good uptake of suramin into the central nervous system at the level of the brainstem. Most of the improvements associated with APT were lost after 5 weeks of drug washout, consistent with the 1-week plasma half-life of suramin in mice. Our results show that purine metabolism is a master regulator of behavior and metabolism in the MIA model, and that single-dose APT with suramin acutely reverses these abnormalities, even in adults.


Animal signals and emotion in music: coordinating affect across groups.
Researchers studying the emotional impact of music have not traditionally been concerned with the principled relationship between form and function in evolved animal signals. The acoustic structure of musical forms is related in important ways to emotion perception, and thus research on non-human animal vocalizations is relevant for understanding emotion in music. Musical behavior occurs in cultural contexts that include many other coordinated activities which mark group identity, and can allow people to communicate within and between social alliances. The emotional impact of music might be best understood as a proximate mechanism serving an ultimately social function. Recent work reveals intimate connections between properties of certain animal signals and evocative aspects of human music, including (1) examinations of the role of nonlinearities (e.g., broadband noise) in non-human animal vocalizations, and the analogous production and perception of these features in human music, and (2) an analysis of group musical performances and possible relationships to non-human animal chorusing and emotional contagion effects. Communicative features in music are likely due primarily to evolutionary by-products of phylogenetically older, but still intact communication systems. But in some cases, such as the coordinated rhythmic sounds produced by groups of musicians, our appreciation and emotional engagement might be driven by an adaptive social signaling system. Future empirical work should examine human musical behavior through the comparative lens of behavioral ecology and an adaptationist cognitive science. By this view, particular coordinated sound combinations generated by musicians exploit evolved perceptual response biases - many shared across species - and proliferate through cultural evolutionary processes.


Incidence and correlates of physical violence among HIV-infected women at risk for pregnancy in the southeastern United States.
To identify the incidence and correlates of physical and sexual violence among HIV-infected women at risk for pregnancy, a cross-sectional examination was conducted within a longitudinal study of reproductive decision making. Participants consisted of 275 HIV-infected women 17 to 49 years of age (mean = 30.1 years). Women were predominantly African American (87%) and single (82%), with annual incomes of $10,000 or less (66%). Overall, 68% of the women reported experiencing lifetime physical and/or sexual violence. Before becoming HIV infected, 65% of the women reported having been physically or sexually abused. After HIV diagnosis, 33% of the women reported experiencing physical or sexual abuse. Women reporting greater violence were more likely to disclose their HIV-seropositive status to their sex partner. Using logistic regression, greater intent to get pregnant (odds ratio [OR] = 0.933), decreased present life satisfaction (OR = 1.048), having three or more children (OR = 0.474), and history of drug use (OR = 0.794) significantly distinguished between women who reported physical and/or sexual violence and those who did not.


Inflammation, insulin resistance, and obesity.
Obesity, in particular visceral obesity, has strong associations with cardiovascular disease and is related to many factors that are constituents of the metabolic syndrome. Increasing evidence suggests that features of the metabolic syndrome, including visceral obesity, are associated with a low-grade inflammatory state. Indeed, visceral fat is a source of several molecules, such as leptin, adiponectin, tumor necrosis factor-alpha, and interleukin 6, that are collectively called adipokines. All of them may induce a proinflammatory state and oxidative damage, leading to initiation and progression of atherosclerosis. Reduced-energy diets might represent an effective and healthful approach for long-term weight loss in patients with metabolic syndrome by reducing the underlying inflammatory condition.