Pharmacological interventions for those who have sexually offended or are at risk of offending.
Sexual offending is a serious social problem, a public health issue, and a major challenge for social policy. Victim surveys indicate high incidence and prevalence levels and it is accepted that there is a high proportion of hidden sexual victimisation. Surveys report high levels of psychiatric morbidity in survivors of sexual offences.Biological treatments of sex offenders include antilibidinal medication, comprising hormonal drugs that have a testosterone-suppressing effect, and non-hormonal drugs that affect libido through other mechanisms. The three main classes of testosterone-suppressing drugs in current use are progestogens, antiandrogens, and gonadotropin-releasing hormone (GnRH) analogues. Medications that affect libido through other means include antipsychotics and serotonergic antidepressants (SSRIs). To evaluate the effects of pharmacological interventions on target sexual behaviour for people who have been convicted or are at risk of sexual offending. We searched CENTRAL (2014, Issue 7), Ovid MEDLINE, EMBASE, and 15 other databases in July 2014. We also searched two trials registers and requested details of unidentified, unpublished, or ongoing studies from investigators and other experts. Prospective controlled trials of antilibidinal medications taken by individuals for the purpose of preventing sexual offences, where the comparator group received a placebo, no treatment, or 'standard care', including psychological treatment. Pairs of authors, working independently, selected studies, extracted data, and assessed the risk of bias of included studies. We contacted study authors for additional information, including details of methods and outcome data. We included seven studies with a total of 138 participants, with data available for 123. Sample sizes ranged from 9 to 37. Judgements for categories of risk of bias varied: concerns were greatest regarding allocation concealment, blinding of outcome assessors, and incomplete outcome data (dropout rates in the five community-based studies ranged from 3% to 54% and results were usually analysed on a per protocol basis).Participant characteristics in the seven studies were heterogeneous, but the vast majority had convictions for sexual offences, ranging from exhibitionism to rape and child molestation.Six studies examined the effectiveness of three testosterone-suppressing drugs: cyproterone acetate (CPA), ethinyl oestradiol (EO), and medroxyprogesterone acetate (MPA); a seventh evaluated two antipsychotics (benperidol and chlorpromazine). Five studies were placebo-controlled; in two, MPA was administered as an adjunctive treatment to a psychological therapy (assertiveness training or imaginal desensitisation). Meta-analysis was not possible due to heterogeneity of interventions, comparators, study designs, and other issues. The quality of the evidence overall was poor. In addition to methodological issues, much evidence was indirect. recividism. Two studies reported recidivism rates formally. One trial of intramuscular MPA plus imaginal desensitisation (ID) found no reports of recividism at two-year follow-up for the intervention group (n = 10 versus one relapse within the group treated by ID alone). A three-armed trial of oral MPA, alone or in combination with psychological treatment, reported a 20% rate of recidivism amongst those in the combined treatment arm (n = 15) and 50% of those in the psychological treatment only group (n = 12). Notably, all those in the 'oral MPA only' arm of this study (n = 5) dropped out immediately, despite treatment being court mandated.Two studies did not report recidivism rates as they both took place in one secure psychiatric facility from which no participant was discharged during the study, whilst another three studies did not appear directly to measure recividism but rather abnormal sexual activity alone. The included studies report a variety of secondary outcomes. Results suggest that the frequency of self reported deviant sexual fantasies may be reduced by testosterone-suppressing drugs, but not the deviancy itself (three studies). Where measured, hormonal levels, particularly levels of testosterone, tended to correlate with measures of sexual activity and with anxiety (two studies). One study measured anxiety formally; one study measured anger or aggression. Adverse events: Six studies provided information on adverse events. No study tested the effects of testosterone-suppressing drugs beyond six to eight months and the cross-over design of some studies may obscure matters (given the 'rebound effect' of some hormonal treatments). Considerable weight gain was reported in two trials of oral MPA and CPA. Side effects of intramuscular MPA led to discontinuation in some participants after three to five injections (the nature of these side effects was not described). Notable increases in depression and excess salivation were reported in one trial of oral MPA. The most severe side effects (extra-pyramidal movement disorders and drowsiness) were reported in a trial of antipsychotic medication for the 12 participants in the study. No deaths or suicide attempts were reported in any study. The latter is important given the association between antilibidinal hormonal medication and mood changes. We found only seven small trials (all published more than 20 years ago) that examined the effects of a limited number of drugs. Investigators reported issues around acceptance and adherence to treatment. We found no studies of the newer drugs currently in use, particularly SSRIs or GnRH analogues. Although there were some encouraging findings in this review, their limitations do not allow firm conclusions to be drawn regarding pharmacological intervention as an effective intervention for reducing sexual offending.The tolerability, even of the testosterone-suppressing drugs, was uncertain given that all studies were small (and therefore underpowered to assess adverse effects) and of limited duration, which is not consistent with current routine clinical practice. Further research is required before it is demonstrated that their administration reduces sexual recidivism and that tolerability is maintained.It is a concern that, despite treatment being mandated in many jurisdictions, evidence for the effectiveness of pharmacological interventions is so sparse and that no RCTs appear to have been published in two decades. New studies are therefore needed and should include trials with larger sample sizes, of longer duration, evaluating newer medications, and with results stratified according to category of sexual offenders. It is important that data are collected on the characteristics of those who refuse and those who drop out, as well as those who complete treatment.


Multi-Grasp Classification for the Control of Robot Hands Employing Transformers and Lightmyography Signals.
The increasing use of smart technical devices in our everyday lives has necessitated the use of muscle-machine interfaces (MuMI) that are intuitive and that can facilitate immersive interactions with these devices. The most common method to develop MuMIs is using Electromyography (EMG) based signals. However, due to several drawbacks of EMG-based interfaces, alternative methods to develop MuMI are being explored. In our previous work, we presented a new MuMI called Lightmyography (LMG), which achieved outstanding results compared to a classic EMG-based interface in a five-gesture classification task. In this study, we extend our previous work experimentally validating the efficiency of the LMG armband in classifying thirty-two different gestures from six participants using a deep learning technique called Temporal Multi-Channel Vision Transformers (TMC-ViT). The efficiency of the proposed model was assessed using accuracy. Moreover, two different undersampling techniques are compared. The proposed thirty-two-gesture classifiers achieve accuracies as high as 92%. Finally, we employ the LMG interface in the real-time control of a robotic hand using ten different gestures, successfully reproducing several grasp types from taxonomy grasps presented in the literature.


Quantitative assessment of MRI lesion load in monitoring the evolution of multiple sclerosis.
In recent years, several segmentation techniques have been developed to quantify brain MRI lesion load in multiple sclerosis and are now being used increasingly for both evaluating the natural history of the disease and monitoring the efficacy of treatment. Such techniques have been applied extensively to conventional T2-weighted images; there is less experience to date with gadolinium-enhanced scans and newer MR parameters which are thought to reflect the more destructive aspects of the pathological process. Manual outlining of lesions on T2-weighted images is moderately accurate when performed by an experienced observer and has been validated in large clinical trials, but is very time consuming. Semi-automated intensity-based techniques appear to be more reproducible, but are still slow to perform. Faster techniques with higher reproducibility are still needed. The correlations between conventional T2 lesion load and clinical outcome is strong in patients seen at first presentation with clinically isolated syndromes suggestive of multiple sclerosis, but much weaker in established multiple sclerosis. The application of quantitative assessment of the MR parameters which are more specific for the disabling aspects of the pathological process (i.e. demyelination, axonal loss and spinal cord involvement) may improve the correlation with clinical status.


Growth and differentiation of myogenic clones from adult human muscle cell cultures.
Clonal cultures only recently have been applied to normal and pathological human muscle, but detailed clonal analysis and differentiative properties of individual long term muscle subclones derived from adult normal human muscle cell (HMC) cultures have not been reported. In this study we compared the growth potential by plating efficiency (PE), muscle colony differentiation (MC) and growth cuvers and the differentiative properties by fusion index, dystrophin localization, creatine kinase (CK) total activity and isozyme electrophoresis in HMC cultures derived myogenic subclones. These properties were tested in two experimental culture systems (200 cells/dish versus single cell/well) and with two tissue culture media (standard medium--MM--versus conditioned medium--CM). We found a significant high PE and MC in clonal cells established with single cell/well and grown in conditioned medium. In derived subclones we observed two classes of myogenic cells: one characterized by exponential growth kinetic, branched myotubes with high fusion index and predominantly sarcolemmal distribution of dystrophin and MM band at CK electrophoresis; the other with flat growth curve, low fusion index and low CK total activity. These findings demonstrate the variability of the expression of myogenic potentials in cells cloned from adult normal HMC cultures and represent an important tool for comparing the various cell types present in normal and diseased human muscle and for transplantation of normal myoblasts in Duchenne Muscular Dystrophy.


Electrically and mechanically tunable electron spins in silicon carbide color centers.
The electron spins of semiconductor defects can have complex interactions with their host, particularly in polar materials like SiC where electrical and mechanical variables are intertwined. By combining pulsed spin resonance with ab initio simulations, we show that spin-spin interactions in 4H-SiC neutral divacancies give rise to spin states with a strong Stark effect, sub-10(-6) strain sensitivity, and highly spin-dependent photoluminescence with intensity contrasts of 15%-36%. These results establish SiC color centers as compelling systems for sensing nanoscale electric and strain fields.


Perceived Utility and Characterization of Personal Google Search Histories to Detect Data Patterns Proximal to a Suicide Attempt in Individuals Who Previously Attempted Suicide: Pilot Cohort Study.
Despite decades of research to better understand suicide risk and to develop detection and prevention methods, suicide is still one of the leading causes of death globally. While large-scale studies using real-world evidence from electronic health records can identify who is at risk, they have not been successful at pinpointing when someone is at risk. Personalized social media and online search history data, by contrast, could provide an ongoing real-world datastream revealing internal thoughts and personal states of mind. We conducted this study to determine the feasibility and acceptability of using personalized online information-seeking behavior in the identification of risk for suicide attempts. This was a cohort survey study to assess attitudes of participants with a prior suicide attempt about using web search data for suicide prevention purposes, dates of lifetime suicide attempts, and an optional one-time download of their past web searches on Google. The study was conducted at the University of Washington School of Medicine Psychiatry Research Offices. The main outcomes were participants' opinions on internet search data for suicide prediction and intervention and any potential change in online information-seeking behavior proximal to a suicide attempt. Individualized nonparametric association analysis was used to assess the magnitude of difference in web search data features derived from time periods proximal (7, 15, 30, and 60 days) to the suicide attempts versus the typical (baseline) search behavior of participants. A total of 62 participants who had attempted suicide in the past agreed to participate in the study. Internet search activity varied from person to person (median 2-24 searches per day). Changes in online search behavior proximal to suicide attempts were evident up to 60 days before attempt. For a subset of attempts (7/30, 23%) search features showed associations from 2 months to a week before the attempt. The top 3 search constructs associated with attempts were online searching patterns (9/30 attempts, 30%), semantic relatedness of search queries to suicide methods (7/30 attempts, 23%), and anger (7/30 attempts, 23%). Participants (40/59, 68%) indicated that use of this personalized web search data for prevention purposes was acceptable with noninvasive potential interventions such as connection to a real person (eg, friend, family member, or counselor); however, concerns were raised about detection accuracy, privacy, and the potential for overly invasive intervention. Changes in online search behavior may be a useful and acceptable means of detecting suicide risk. Personalized analysis of online information-seeking behavior showed notable changes in search behavior and search terms that are tied to early warning signs of suicide and are evident 2 months to 7 days before a suicide attempt.


Neutrophil influx during non-typhoidal salmonellosis: who is in the driver's seat?
A massive neutrophil influx in the intestine is the histopathological hallmark of Salmonella enterica serovar Typhimurium-induced enterocolitis in humans. Two major hypotheses on the mechanism leading to neutrophil infiltration in the intestinal mucosa have emerged. One hypothesis suggests that S. enterica serovar Typhimurium takes an active role in triggering this host response by injecting proteins, termed effectors, into the host cell cytosol which induce a proinflammatory gene expression profile in the intestinal epithelium. The second hypothesis suggests a more passive role for the pathogen by proposing that bacterial invasion stimulates the innate pathways of inflammation because the pathogen-associated molecular patterns of S. enterica serovar Typhimurium are recognized by pathogen recognition receptors on cells in the lamina propria. A review of the current literature reveals that, while pathogen recognition receptors are clearly involved in eliciting neutrophil influx during S. enterica serovar Typhimurium infection, a direct contribution of effectors in triggering proinflammatory host cell responses cannot currently be ruled out.


Risk of Early Versus Later Rebleeding From Dural Arteriovenous Fistulas With Cortical Venous Drainage.
Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quantify the relative incidence of rebleeding in the early and later periods following hemorrhage. Patients with dural arteriovenous fistula and cortical venous drainage presenting with hemorrhage were identified from the multinational CONDOR (Consortium for Dural Fistula Outcomes Research) database. Natural history follow-up was defined as time from hemorrhage to first treatment, rebleed, or last follow-up. Rebleeding in the first 2 weeks and first year were compared using incidence rate ratio and difference. Of 1077 patients, 250 met the inclusion criteria and had 95 cumulative person-years natural history follow-up. The overall annualized rebleed rate was 7.3% (95% CI, 3.2-14.5). The incidence rate of rebleeding in the first 2 weeks was 0.0011 per person-day; an early rebleed risk of 1.6% in the first 14 days (95% CI, 0.3-5.1). For the remainder of the first year, the incidence rate was 0.00015 per person-day; a rebleed rate of 5.3% (CI, 1.7-12.4) over 1 year. The incidence rate ratio was 7.3 (95% CI, 1.4-37.7; P, 0.026). The risk of rebleeding of a dural arteriovenous fistula with cortical venous drainage presenting with hemorrhage is increased in the first 2 weeks justifying early treatment. However, the magnitude of this increase may be considerably lower than previously thought. Treatment within 5 days was associated with a low rate of rebleeding and appears an appropriate timeframe.


Avocado oil (Persea americana) protects SH-SY5Y cells against cytotoxicity triggered by cortisol by the modulation of BDNF, oxidative stress, and apoptosis molecules.
Chronic psycho-environmental stress can induce neurological dysfunction due to an increase in cortisol levels. It is possible that some food supplements could attenuate its negative impact, such as avocado oil (AO), which is rich in fatty acids with beneficial effects on the brain. This hypothesis was tested by an in vitro model using undifferentiated neuroblastoma cells (SH-SY5Y) exposed to hydrocortisone (HC), an active cortisol molecule with and without AO-supplementation. Cortisol can induce oxidative stress, apoptosis events, and a lowering effect on brain-derived neurotrophic factor (BDNF), a neurogenic molecule. As AO protective effects on HC-exposed cells could involve these routes, some markers of these routes were compared among neuroblastoma cultures. In the first assay, the range concentrations of HC exposure that trigger cell mortality and range AO-concentrations that could revert the HC effect. AO at all concentrations tested (2-30 µg/ml) did not present a cytotoxic effect on SH-SY5Y cells, whereas HC at 0.3-10 ng/ml had a dose-dependent cytotoxic effect on these cells. From these results, HC at 10 ng/ml and AO at 5 µg/ml were chosen for mechanistic analysis. AO was able to decrease the oxidative molecules; however, both AO- and HC-induced differential and varied gene expression modulation of these enzymes. AO partially reverted the protein and gene expression of apoptotic markers that were higher in HC-exposed cells. AO also increases the BDNF levels, which are lower HC-exposed cultures. The results indicate that AO could be a beneficial supplement in situations where cortisol levels are elevated, including chronic psycho-environmental stress. PRACTICAL APPLICATIONS: Psychological chronic stress that induces high cortisol exposure has been linked to premature aging and decreased healthy life expectancy. Neurobiological models involving cortisol have suggested a neurotoxic effect of this molecule, increasing the risk of psychiatric and other CNTDs. This effect can have a high impact mainly in infants and elderly people. In child abuse situations, chronic cortisol exposure could induce extensive apoptosis events, causing impairment in synaptogenesis. In both age groups, chronic cortisol exposure increased the risk of psychiatric conditions, especially anxiety and major depression. However, it is possible that the negative effects associated with chronic cortisol exposure could be attenuated by some food supplements. This is the case for molecules acquired through diet, such as polyunsaturated fatty acids (PUFAs), including omega-3. As inadequate omega-3 levels in the brain can increase the risk factor for neuropsychiatric disorders, it is possible to infer that some from food supplements, such as avocado oil, could attenuate the neurotoxic effects of chronic cortisol exposure. This hypothesis was tested using an exploratory in vitro protocol, and the results suggested that avocado oil could be used as a cytoprotective food supplement by decreasing the oxidative stress and apoptotic events induced by cortisol.


Thrombospondin 2/Toll-Like Receptor 4 Axis Contributes to HIF-1α-Derived Glycolysis in Colorectal Cancer.
Aerobic glycolysis is a typical metabolic reprogramming in tumor cells, which contributes to the survival and proliferation of tumor cells. The underlying mechanisms controlling this metabolic switch in colorectal cancer (CRC), however, remain only partially understood. The Cancer Genome Atlas (TCGA) dataset and Gene Expression Omnibus (GEO) (GDS4382, GSE6988, GSE35834) were used to analyzed the mRNA expression of THBS2. 392 paired samples of CRC and adjacent non-cancerous tissues were collected to detect the expression of THBS2 by IHC. The correlation of THBS2 expression with categorical clinical variables in patients with CRC was evaluated using chi-square analysis or Student's t-test. CCK-8, colony formation, and animal CT scan were used to functional analysis of THBS2 in CRC. Thrombospondin 2 (THBS2) is aberrantly upregulated and linked to a poor prognosis in CRC. Subsequent experiments also showed that THBS2 promotes the proliferation of CRC cells. In terms of mechanism, THBS2 interacted with Toll-like receptor 4 (TLR4), but not with the other toll-like receptors (TLRs), which upregulated the mRNA expression of GLUT1, HK2, ALDOA, PKM2, and LDHA and enhanced glycolytic capacity in CRC cells. Moreover, THBS2/TLR4 axis significantly increased the protein level of HIF-1α and blocking HIF-1α by siRNA reversed the enhanced glycolytic capacity and the upregulated expression of glycolytic enzymes in CRC cells. Our findings revealed that the THBS2/TLR4 axis contributes to HIF-1α derived glycolysis and eventually promotes CRC progress.


Nucleotide sequence of the tail tube structural gene of bacteriophage T4.
The nucleotide sequence of gene 19 of bacteriophage T4, the structural gene of the tail tube protein, was determined by both the dideoxy and the Maxam-Gilbert methods. The predicted Mr of tube protein gene product 19 is 18,842. The N-terminal amino acid of the tube protein was determined by Edman degradation, and the C-terminal sequence was confirmed by isolation of the C-terminal tryptic peptide. In the noncoding region between genes 18 and 19, there are two late-T4-promoter consensus sequences, 51 bases apart. The implication of the two late promoter sequences was examined by an S1 nuclease protection experiment. Both serve as weak promoters, but the bulk of the transcripts arise from further upstream of the two promoters.


Traumatic Dental Injuries Prevalence and their Impact on Self-esteem among Adolescents in India: A Comparative Study.
Adolescents are mostly injured during sport activities, traffic accidents and some forms of violence which may lead to traumatic injuries. Traumatic injuries not only pose a health risk worldwide but are also regarded among serious social problems. Poor oral health has been related to poor social relationships that affect the ability to learn and grow which may lead to reduced self-esteem. This study was conducted to compare self-esteem of adolescents with and without anterior Traumatic Dental Injury (TDI). A population based comparative study was conducted among 10 to 17 years old adolescents from November 2014 to January 2016. The study sample comprised of 424 controls and 212 cases with 2:1 control-to-case ratio that were selected by four examiners along with a gold standard examiner. TDI was recorded using Ellis classification and self-esteem was recorded using Rosenberg's Self-Esteem Scale (RSES). For comparing self-esteem of cases and controls according to RSES questions, t-test is used. Odds ratio (OR) was utilized to assess and compare the self-esteem according to high and low esteem in cases and controls. Ellis Class I, Ellis Class II and Ellis Class III fractures were observed in 53.3%, 33.49% and 13.20% of cases, respectively. The maxillary arch was the most affected (72.48%) and on the hierarchy of causes, this study found that on most occasions dental injuries were caused by sports (40.09%). The total mean score of RSES in cases (23.16) and in controls (24.43) was also statistically significant (p<0.001). Improving oral health in schools may contribute considerably to increase the self-esteem of adolescents in a positive direction and help them in becoming socially competent adults.


Discharge patterns, survival outcomes, and changes in clinical management of hospitalized adult patients with cancer with a do-not-resuscitate order.
Do-not-resuscitate (DNR) orders prevent medically futile attempts at resuscitation but are not always instituted in hospitalized patients with advanced cancer. One explanation for this underuse is the perception that DNR orders are inevitably associated with withdrawal of all medical interventions and inpatient death. To audit discharge and survival outcomes and changes in clinical management in hospitalized adult oncology patients with a DNR order, allowing an assessment of whether such orders lead to cessation of acute interventions and high rates of in-hospital death. Retrospective data were collected from 270 oncology inpatients at Austin Health, Melbourne, Australia, between February 1, 2012 and November 30, 2012. Mean and median time to institution of DNR orders after admission were 2.1 and 1.0 days, respectively (interquartile range, 0-2 days). Medical interventions continued in 80% or more of cases after DNR orders were placed included blood draws, intravenous antimicrobials, imaging, blood products, and radiotherapy. Two-thirds of patients survived hospitalization and were discharged alive. Survival at 30 days and 90 days after DNR orders were implemented was 63% and 33%, respectively. Baseline Charlson Comorbidity Index score of 5 or less and Eastern Cooperative Oncology Group performance status of 2 or less were associated with a higher probability of being discharged alive and longer overall survival. Most medical interventions were continued with high frequency in adult oncology inpatients after placement of DNR orders. A majority of patients survived hospitalization and remained alive at 30 days after DNR orders were documented. This study offers some reassurance that DNR orders do not inevitably lead to cessation of appropriate medical treatment.


Feline visceral hemangiosarcoma.
Feline visceral hemangiosarcoma (HSA) is an uncommon tumor, and the clinical progression and outcome are rarely reported. The prognosis of feline visceral HSA is poor because of severe clinical signs, anemia, and a high rate of metastasis. The medical records of 26 client-owned cats with visceral HSA were reviewed. Multi-institutional retrospective study. The most common historical findings and clinical signs included lethargy, anorexia, respiratory difficulty, collapse, and vocalizing. Eighty-two percent of cats were anemic, and aspartate transaminase was increased in 53% of the study population. Metastatic lung disease was noted in 33% of affected cats. In 75% of the cats, abdominal ultrasonography identified a specific location of HSA. However, ultrasound identification of all multifocal lesions was successful only in 3/9 cats (33%). Tumor location was identified in the following organs: liver (35%), small intestine (31%), large intestine (31%), abdominal lymph node (31%), mesentery (27%), spleen (23%), lung (19%), omentum (12%), brain (8%), pancreas (8%), and diaphragm (8%). Multifocal HSA was noted in 77% of cats. Three cats received adjuvant chemotherapy (doxorubicin). Seventy-one percent of euthanized cats were euthanized within 1 day of diagnosis. The median survival time of the remaining cats (n = 6) was 77 days (range, 23-296 days). Feline visceral HSA is most often multifocal at the time of diagnosis. The prognosis appears poor, and the number of cats receiving chemotherapy is low.


Prevalence and predictors of depression, anxiety, and stress symptoms among pregnant women during COVID-19-related lockdown in Abakaliki, Nigeria.
Several studies have been published on the topic of COVID-19 and pregnancy over recent months. However, few studies have evaluated the impact of this pandemic on maternal mental health, particularly in low-resource settings. To determine the prevalence and predictors of COVID-19-related depression, anxiety and stress symptoms among pregnant women. This was a cross-sectional study that involved 456 pregnant women attending prenatal care at Abakaliki, Nigeria, during the COVID-19 lockdown. These patients were screened for psychological morbidities using the Depression Anxiety and Stress Scale-21 (DASS-21). Severe and extremely severe depression were reported in 7.2% (n=33) and 6.4% (n=29) of participants, respectively. Analysis also revealed that 3.3% (n=15) and 7.7% (n=35) of women had severe and extremely severe anxiety, respectively. In total, 23% (n=105) of the participating women had severe stress while 16.7% (n=76) reported extremely severe stress. Multiparity (2-4) and occupation, such as trading and farming, were predictors of depression whereas grand-multiparity, urban residence, and trading, were identified as predictors of anxiety and stress. Symptoms of depression, anxiety and stress were relatively common among pregnant women during the COVID-19 lockdown in Abakaliki, Nigeria. There is a clear need to integrate screening for depression, anxiety and stress, in existing antenatal care programs so as to identify and prevent long-term adverse psychological outcomes related to the COVID-19 pandemic.


[Thermodynamic and spectral study of DNA-prospidin complex].
By the methods of heat denaturation and luminescence the interaction between an antitumor drug prospidine and DNA in aqueous solutions at two ionic strengths (0.1 and 0.001 M NaCl) and at various prospidine concentrations was studied. For the first time it has been demonstrated that the interaction occurs at 0.1 M NaCl and therapeutic prospidine concentrations. In the framework of Frank-Kamenetsky's theory of melting of a polymer with stabilizing ligands the size of the binding site and binding constants (K) with the decrease of ionic strength, the lack of alterations in the DNA UV absorption spectrum on complex formation and the data on the competitive binding of ethydium bromide suggest that at the first stage of the reaction an external complex is formed due to electrostatic interactions between quaternary nitrogen atoms of prospidine and DNA phosphate groups. Incubation of the complex at 37 0 C leads to a decrease of the DNA melting temperature and hyperchromic effect. Presumably this is due to the relatively slow formation of chemical bonds between alkylating groups of prospidine and nucleophilic groups of DNA bases, which results in the destabilization and denaturation of DNA. It is concluded that the interaction between prospidine and DNA must be taken into consideration when studying the molecular mechanism of prospidine antitumour activity.


[Surgical and combined treatment of kidney cancer].
A comparative analysis of two clinical groups of patients was performed in order to study the influence of postoperative irradiation on the results of the treatment of only the surgical treatment (nephrectomy). The second group (63 patients) was subjected to a combined treatment - nephrectomy and irradiation. In the first group the survival rate for 3 and 5 years was 40,0% and 20,0%, in the second group-49,9% and 31,7% respectively. The survival rate was higher in the combined treatment because of less recidivation of carcinoma (14,3%), although the frequency of the metastatic spread in the both groups was almost the same-50,6% and 54,0%.


Ultramarathon run markedly reduces plasma sphingosine-1-phosphate concentration.
We have previously shown that acute exercise increases the level of sphingosine-1-phosphate (S1P) in plasma and ceramide in erythrocytes of untrained subjects. The aim of the current study was to examine the effect of ultramarathon run on the plasma and erythrocyte levels of the following bioactive sphingolipids: S1P, sphinganine-1-phosphate (SA1P), sphingosine, sphinganine, and ceramide. Blood samples were collected from seven male amateur runners participating in a 48-hr ultramarathon race before the run, after 24 and 48 hr of running, and following 24 and 48 hr of recovery. The sphingolipids were quantified by means of HPLC. Sustained running for 48 hr resulted in a progressive decline in plasma S1P to a level significantly lower than at prerace, and then remained stable over the next 48 hr of recovery. In erythrocytes, S1P content was stable until 24 hr of recovery, then rose abruptly to reach peak values after 48 hr of recovery. The plasma level of SA1P decreased progressively during the competition and remained unchanged over the recovery. In erythrocytes, the level of SA1P increased after 24 hr running and normalized thereafter. The level of ceramide, both in plasma and erythrocytes, was not significantly affected by the ultraendurance run. We speculate that reduction in plasma level of S1P during and after the run reduces its biological actions and might be responsible for some negative side-effects of the ultraendurance effort.


Bilateral Transcranial Magnetic Stimulation of the Prefrontal Cortex Reduces Cocaine Intake: A Pilot Study.
Chronic cocaine consumption is associated with a decrease in mesolimbic dopamine transmission that maintains drug intake. transcranial magnetic stimulation (TMS) is gaining reliability, a useful therapeutic tool in drug addiction, since it can modulate cortico-limbic activity resulting in reduction of drug craving. In the present study, we investigated the therapeutic effect of bilateral TMS of prefrontal cortex (PFC) in reducing cocaine intake, in a sample of treatment-seeking patients with current cocaine use disorder (DSM-V). Ten cocaine addicts (DSM-V) were randomly assigned to the active or sham stimulation protocol in a double-blind experimental design. Twelve repetitive TMS (rTMS) sessions were administered three times a week for 4 weeks at 100% of motor threshold, over bilateral PFC. Cocaine intake (ng/mg) was assessed by hair analysis at baseline (before treatment, T0), after 1 month (end of treatment, T1), 3 (T2), and 6 (T3) months later. All subjects received psychological support weekly. The two-way ANOVA for repeated measures did not show a significant effect of the interaction between time and treatment (F 4,32 = 0.35; p = 0.87). Despite that result indicated no difference in the effect of the two conditions (active vs. sham) along time, a decreasing trend in cocaine consumption in active TMS group (F 3,23 = 3.42; p = 0.04) vs. sham (F 3,15 = 1.88; p = 0.20) was observed when we performed exploratory analysis with time as factor. Indeed, Post hoc comparisons showed a significant reduction in the amount of cocaine detected from the onset to 3 months later (T0-T2; p = 0.02) and to the end of treatment (T0-T3; p = 0.01) in addicts from the active group. Bilateral rTMS of PFC at 10 Hz did not show a significant effect on cocaine intake compared to sham. However, a long-term reduction on cocaine intake in active TMS-treated patients was observed when we considered the time as factor. Further studies are required to confirm these encouraging but preliminary findings, in order to consolidate rTMS as a valid tool to treat cocaine addiction.


Variable cultural acquisition costs constrain cumulative cultural evolution.
One of the hallmarks of the human species is our capacity for cumulative culture, in which beneficial knowledge and technology is accumulated over successive generations. Yet previous analyses of cumulative cultural change have failed to consider the possibility that as cultural complexity accumulates, it becomes increasingly costly for each new generation to acquire from the previous generation. In principle this may result in an upper limit on the cultural complexity that can be accumulated, at which point accumulated knowledge is so costly and time-consuming to acquire that further innovation is not possible. In this paper I first review existing empirical analyses of the history of science and technology that support the possibility that cultural acquisition costs may constrain cumulative cultural evolution. I then present macroscopic and individual-based models of cumulative cultural evolution that explore the consequences of this assumption of variable cultural acquisition costs, showing that making acquisition costs vary with cultural complexity causes the latter to reach an upper limit above which no further innovation can occur. These models further explore the consequences of different cultural transmission rules (directly biased, indirectly biased and unbiased transmission), population size, and cultural innovations that themselves reduce innovation or acquisition costs.


Demographic assessment of the Dalmatian dog - effective population size, linkage disequilibrium and inbreeding coefficients.
The calculation of demographic measures is a useful tool for evaluating the genomic architecture of dog breeds and enables ranking dog breeds in terms of genetic diversity. To achieve this for the German Dalmatian dog population, 307 purebred animals of this breed were genotyped on the Illumina Canine high density BeadChip. The analysis of pedigree-based inbreeding was performed based on a pedigree with 25,761 dogs including the genotyped dogs. The effective population size derived from squared correlation coefficients between SNP alleles (r 2) was 69. The maximum value of r 2 was 0.56, resulting in a 50% decay value of 0.28 at a marker distance of 37.5 kb. The effective population size calculated from pedigree data using individual increase in inbreeding over equivalent generations was 116. The pedigree inbreeding coefficient was 0.026. The genomic inbreeding coefficient based on the length of runs of homozygosity (ROH) was calculated for seven length categories of ROHs, and ranged from 0.08 to 0.28. The fixation coefficients FIS_PED and FIS_GENO were at 0.017 and 0.004. PANTHER statistical overrepresentation analysis of genes located in consensus ROHs revealed highly underrepresented biological processes in 50% of the investigated dogs. One of those is the 0.28 fold enriched "immune response", which might be associated to the high prevalence of allergic dermatitis in the breed. Candidate genes for congenital sensorineural deafness (CCSD, a highly prevalent disease in the Dalmatian) were discovered in consensus ROHs. The fast decay of r 2 and the moderate inbreeding coefficients indicate that the German Dalmatian dog population is rather diverse. Pedigree- and genomic-based inbreeding measures were highly correlated and therefore prove good reliability for the given population. Analyses of consensus ROHs with genes coding for deafness and other breed-defining traits, such as hyperuricosuria, indicate that those ROH became fixed in the Dalmatian population about 500 years ago. In case of the Dalmatian dog, a ROH of 40 SNPs length is enough to investigate signatures of selection (e.g. the ROH with the fixed hyperuricosuria mutation) as far back as the breed formation point approximately 500 years ago.


Calcium phosphate cement reinforcement by polymer infiltration and in situ curing: a method for 3D scaffold reinforcement.
This study describes a novel method of calcium phosphate cement reinforcement based on infiltrating a pre-set cement with a reactive polymer and then cross-linking the polymer in situ. This method can be used to reinforce 3D calcium phosphate cement scaffolds, which we demonstrate using poly(ethylene glycol) diacrylate (PEGDA) as a model reinforcing polymer. The compressive strength of a 3D scaffold comprised of orthogonally intersecting beams was increased from 0.31 +/- 0.06 MPa to 1.65 +/- 0.13 MPa using PEGDA 600. In addition, the mechanical properties of reinforced cement were characterized using three PEGDA molecular weights (200, 400, and 600 Da) and three cement powder to liquid (P/L) ratios (0.8, 1.0, and 1.43). Higher molecular weight increased reinforcement efficacy, and P/L controlled cement porosity and determined the extent of polymer incorporation. Although increasing polymer incorporation resulted in a transition from brittle, cement-like behavior to ductile, polymer-like behavior, maximizing polymer incorporation was not advantageous. Polymerization shrinkage produced microcracks in the cement, which reduced the mechanical properties. The most effective reinforcement was achieved with P/L of 1.43 and PEGDA 600. In this group, flexural strength increased from 0.44 +/- 0.12 MPa to 7.04 +/- 0.51 MPa, maximum displacement from 0.05 +/- 0.01 mm to 1.44 +/- 0.17 mm, and work of fracture from 0.64 +/- 0.10 J/m(2) to 677.96 +/- 70.88 J/m(2) compared to non-reinforced controls. These results demonstrate the effectiveness of our novel reinforcement method, as well as its potential for fabricating reinforced 3D calcium phosphate cement scaffolds useful for bone tissue engineering.


Localisation of experimental staphylococcal abscesses by 99MTC-technetium-labelled liposomes.
The accumulation of 99mTc-technetium-labelled liposomes in abscesses was studied. Abscesses were produced in the thighs of albino rats by intramuscular injection of Staphylococcus aureus. After 4 days these abscesses were used to determine the localisation of 99mTc-technetium-labelled anionic, cationic and neutral liposomes in the abscess area. This was achieved by radionuclide images produced by a gamma camera and an associated data-processing system. There was a pronounced uptake of 99mTc-technetium-labelled anionic liposomes in the abscess area compared with the corresponding unaffected thigh. Similar uptake was not shown by the 99mTc-technetium-labelled cationic and neutral liposomes. Abscess uptake of anionic liposomes was maximal at or before 30 min after injection and was not enhanced by prior opsonisation with aggregated rat immunoglobulin.


Experimental design approach to evaluate the impact of oak chips and micro-oxygenation on the volatile profile of red wines.
A chemometric strategy based on combining an experimental design approach and response surface methodology was applied to gain further knowledge on the influence of chip maceration and micro-oxygenation related factors (oxygen doses, chip doses, wood origin, toasting degree and maceration time) on the volatile profile of red wines during the accelerated ageing process. The results obtained indicated that the volatile profile of wines could be modulated by applying different combinations of factor conditions. Thus, these results would be used to obtain wines with specific volatile profiles that would lead to particular olfactory attributes according to consumers' preferences. Moreover, it was shown that combining wood from different origins helped enhance the quality of the elaborated wines. To the best of our knowledge, this is the first time that an experimental design methodology has been applied to simultaneously evaluate the influence of five different ageing parameters on the volatile profile of red wines.


Biomechanical considerations of prosthodontic therapy: the urgency of research into alveolar bone responses.
The prognosis of natural and implant abutments depends in part on the complementary and/or antagonistic biomechanic and calcium homeostatic functions of the adjacent alveolar bone. Whereas bone morphology is determined by peak strains, strain rates, and strain distributions, infrequent error strains on abutments have a greater impact on the adjacent alveolar bone than those generated during "normal" activity. Alveolar responses depend on the immediate prevailing systemic and local demands, although unexpected abutment failures will continue until such influences have been investigated further.


The effect of intervention on the free-play experience for mothers and their infants with developmental delay and cerebral palsy.
An intervention study designed to investigate the effects of one hour of maternal and infant behavior was conducted using experimental and control groups of mothers and their infants with cerebral palsy. Ten mother-infant pairs were in each group; infants ranged in age from 8-32 months. Infants of mothers in the control group received one hour of NDT-based occupational therapy. Two-factor repeated measures analysis of variance with repeated measures of the second factor indicated that the nonverbal instruction methods were significantly more successful in modifying maternal and infant behavior than were the verbal instruction methods. Implications of the results for intervention programs and future research were discussed.


Estradiol improves right ventricular function in rats with severe angioproliferative pulmonary hypertension: effects of endogenous and exogenous sex hormones.
Estrogens are disease modifiers in PAH. Even though female patients exhibit better right ventricular (RV) function than men, estrogen effects on RV function (a major determinant of survival in PAH) are incompletely characterized. We sought to determine whether sex differences exist in RV function in the SuHx model of PAH, whether hormone depletion in females worsens RV function, and whether E2 repletion improves RV adaptation. Furthermore, we studied the contribution of ERs in mediating E2's RV effects. SuHx-induced pulmonary hypertension (SuHx-PH) was induced in male and female Sprague-Dawley rats as well as OVX females with or without concomitant E2 repletion (75 μg·kg(-1)·day(-1)). Female SuHx rats exhibited superior CI than SuHx males. OVX worsened SuHx-induced decreases in CI and SuHx-induced increases in RVH and inflammation (MCP-1 and IL-6). E2 repletion in OVX rats attenuated SuHx-induced increases in RV systolic pressure (RVSP), RVH, and pulmonary artery remodeling and improved CI and exercise capacity (V̇o2max). Furthermore, E2 repletion ameliorated SuHx-induced alterations in RV glutathione activation, proapoptotic signaling, cytoplasmic glycolysis, and proinflammatory cytokine expression. Expression of ERα in RV was decreased in SuHx-OVX but was restored upon E2 repletion. RV ERα expression was inversely correlated with RVSP and RVH and positively correlated with CO and apelin RNA levels. RV-protective E2 effects observed in females were recapitulated in male SuHx rats treated with E2 or with pharmacological ERα or ERβ agonists. Our data suggest significant RV-protective ER-mediated effects of E2 in a model of severe PH.


Impact of parameter variation in fabrication of nanostructure by atomic force microscopy nanolithography.
In this letter, we investigate the fabrication of Silicon nanostructure patterned on lightly doped (10(15) cm(-3)) p-type silicon-on-insulator by atomic force microscope nanolithography technique. The local anodic oxidation followed by two wet etching steps, potassium hydroxide etching for silicon removal and hydrofluoric etching for oxide removal, are implemented to reach the structures. The impact of contributing parameters in oxidation such as tip materials, applying voltage on the tip, relative humidity and exposure time are studied. The effect of the etchant concentration (10% to 30% wt) of potassium hydroxide and its mixture with isopropyl alcohol (10%vol. IPA ) at different temperatures on silicon surface are expressed. For different KOH concentrations, the effect of etching with the IPA admixture and the effect of the immersing time in the etching process on the structure are investigated. The etching processes are accurately optimized by 30%wt. KOH +10%vol. IPA in appropriate time, temperature, and humidity.


Cooperative nest defence in red-winged blackbirds: reciprocal altruism, kinship or by-product mutualism?
Male red-winged blackbirds (Agelaius phoeniceus) often cooperate with their neighbours in defending nests against predators. Some studies have suggested that this is an example of by-product mutualism, whereas others have suggested the possibility of reciprocal altruism. No study has addressed the possibility of kin-selected cooperation in nest defence in this species. Reciprocal altruism, kin selection and by-product mutualism are not mutually exclusive alternatives, but few studies of territorial neighbours have tested for multiple mechanisms simultaneously. We test for these three possibilities in a population of red-winged blackbirds. We used simulated defections to test for reciprocal altruism. We used analysis of microsatellite loci to test for kin selection between adult male neighbours. We also used microsatellite loci to test for by-product mutualism resulting from nest defence of offspring sired on neighbouring territories. We found that male red-winged blackbirds cooperate in nest defence primarily as a form of reciprocal altruism. Experimental males reduced their level of nest defence relative to controls following simulated defection by a neighbour. In contrast to some earlier studies, we found no evidence for by-product mutualism: males did not defend nests where they had sired extra-pair offspring. We also found no evidence for kin selection: males were no more cooperative with more closely related neighbours. Considered alongside the results from other studies, our study suggests that mechanisms stabilizing cooperation in red-winged blackbirds may vary among populations.


Acetylcholine release during burst-patterned stimulation of a sympathetic ganglion: its relation to transmission efficiency.
The time-course of increase in acetylcholine (ACh) output during burst-patterned preganglionic stimulation of the cat superior cervical ganglion has been determined. The increase in output corresponded closely with the increase in transmission efficiency found earlier in the stellate ganglion subjected to similar preganglionic stimulation. ACh output however continued to increase following the time of attainment of full neuronal recruitment. The results indicate that the increase in ACh output may largely account for the increase in transmission; but they leave unexplained the synaptic function of the continuing increase in transmitter release.


Measuring of a three-dimensional surface by use of a spatial distance computation.
The correspondence problem of two captured images, which are obtained by projecting a structured light on the measuring surface, are explored for when three-dimensional information of a given surface is needed. In our system the constraint that codifies the pattern projected on the surface has been simplified by using a random speckle pattern, thus the correspondence problem is reduced tolocal matching between two captured images and solved by a spatial distance computation technique. The performance of our approach, which includes a disparity error analysis, a search range suggestion, and a disparity gradient limit, are investigated and discussed. Some parameters, such as percentile constraint, sampling interval, and subpixel compensation proper for use in this approach are suggested. Experiments have shown the feasibility of the proposed method.


Atraumatic osteonecrosis of the patella.
Atraumatic secondary osteonecrosis of the patella is a rare entity and has been reported in only several case reports. The purpose of this study was to define the clinical and radiographic characteristics and outcome of this disease. Osteonecrosis of the patella was found in 25 knees in 19 patients. The mean age was 42 years (range, 21-63 years). Eighteen (95%) patients had greater than 2 g of lifetime corticosteroid exposure, and six (32%) patients had systemic lupus erythematosus. Osteonecrosis was found in the superior pole of the patella in all 23 knees (17 patients) that had magnetic resonance imaging. Osteonecrosis was apparent on plain radiographs in five knees (20%) in four patients, and only one knee (4%) in one patient had collapse of the posterior articulating surface of the patella. One (4%) patient presented with anterior knee pain localized to the patella. At a mean followup of 4 years (range, 2-18 years), none of the patients had an intervention that focused on treating the patellar lesion. Patellar osteonecrosis is characterized by patients with coincident lesions of the distal femur and the proximal tibia and lesions localized to the superior pole of the patella. It is a nonprogressive disease that does not warrant surgical exploration.


No evidence that mask-wearing in public places elicits risk compensation behavior during the COVID-19 pandemic.
Face masks have been widely employed as a personal protective measure during the COVID-19 pandemic. However, concerns remain that masks create a false sense of security that reduces adherence to other public health measures, including social distancing. This paper tested whether mask-wearing was negatively associated with social distancing compliance. In two studies, we combined video-observational records of public mask-wearing in two Dutch cities with a natural-experimental approach to evaluate the effect of an area-based mask mandate. We found no observational evidence of an association between mask-wearing and social distancing but found a positive link between crowding and social distancing violations. Our natural-experimental analysis showed that an area-based mask mandate did not significantly affect social distancing or crowding levels. Our results alleviate the concern that mask use reduces social distancing compliance or increases crowding levels. On the other hand, crowding reduction may be a viable strategy to mitigate social distancing violations.


A comparison of the efficacy of naftopidil and tamsulosin hydrochloride in medical treatment of benign prostatic enlargement.
Lower urinary tract symptoms in men, over age of 50 years is suggestive of benign prostatic enlargement (BPE). Different alpha-blockers have been evaluated for the treatment of benign prostatic hyperplasia for over last 30 years. This study was conducted in a tertiary care institution during the period of year between June 2011 and August 2013 to compare the effect of naftopidil and tamsulosin in reducing the obstructive and irritable symptoms of BPE. A prospective randomized comparative study was carried on 60 patients of BPE by assigning half of them to treatment with tamsulosin and rest with naftopidil. Pre- and post-treatment uroflowmetry (UFM), post-void residue (PVR), International Prostate Symptoms Score (IPSS), were obtained at 15 and 30 days after starting treatment. The age of patients ranged from 51 to 78. At base line there was no statistical difference between UFM parameter, PVR and IPSS in the two groups. UFM and PVR showed significantly better response at both intervals with naftopidil. Comparison of IPSS showed better improvement in Group A both at 15 and 30 days. It was seen that the obstructive symptoms showed a significantly better response with tamsulosin and symptoms of irritability was seen better response with naftopidil. It was seen that during the period of follow-up of 30 days naftopidil had a better effect on UFM, PVR, IPSS compared with tamsulosin. In general, obstructive symptoms showed better improvement in tamsulosin and irritative symptoms showed better improvement in naftopidil.


Differential growth of the fungus Absidia cylindrospora on 13C/15N-labelled media.
Many studies utilise enrichment of stable isotopes as tracers to follow the interactions occurring within soil food webs and methods have been developed to enrich bacteria, soil fauna and plant litter, Here for the first time we attempt to enrich a soil fungus to 99 atom% with (13)C and (15)N stable isotopes. In this study our objectives were to (a) assess whether the saprotrophic zygomycete fungus Absidia cylindrospora could grow on a medium enriched to 99 atom% with (13)C-glucose and (15)N-ammonium chloride, (b) to determine the level of enrichment obtained, and (c) to examine the change in growth rate of this fungus while it was growing on the dually enriched medium. To achieve this, the fungus was grown on agar enriched with (13)C and (15)N to 99 atom% and its growth rate monitored. The results showed that A. cylindrospora would grow on the highly labelled growth medium, but that its rate of growth was affected compared with the rate on either natural abundance media or media highly enriched with a single isotope ((13)C or (15)N). The implications of these results is that although the fungus is able to utilise these heavier isotopes, the biochemical processes involved in growth are affected, and consideration should be given to these differences when using stable isotope tracers in, for example, soil food web studies.


FDG PET-CT for lymph node staging of bladder cancer: a prospective study of patients with extended pelvic lymphadenectomy.
The purpose of this study was to evaluate the diagnostic accuracy of [(18)F] fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) for lymph node (LN) staging of bladder cancer patients undergoing radical cystectomy (RC) with extended pelvic lymphadenectomy compared to conventional CT. A total of 61 patients underwent FDG PET-CT before RC and extended pelvic lymphadenectomy. A template for extended pelvic lymphadenectomy to the level of the inferior mesenteric artery was divided into 11 anatomic nodal packets. Definitive pathologic findings of resected LNs were correlated with the results of FDG PET-CT and CT alone in a patient- and nodal packet-based manner. Among the 61 patients, pathological staging confirmed LN metastasis in 17 patients (27.9 %). In total, 627 LN packets (2580 LNs) were resected and histologically evaluated. The mean number of LNs removed was 42 (median 40; range 22-118). Of the 627 LN packets removed, 27 packets (4.3 %) were positive for LN metastasis based on pathologic analysis. On a patient-based analysis, FDG PET-CT and conventional CT showed a sensitivity of 47.1 and 29.4 %, respectively, specificity of 93.2 and 97.7 %, respectively, positive predictive value (PPV) of 72.7 and 78.2 %, respectively, and negative predictive value (NPV) of 82.0 and 78.2 %, respectively. On a nodal packet-based analysis, sensitivity, specificity, PPV, and NPV were 14.8, 97.8, 23.5, and 96.2 %, respectively, for PET-CT and 11.1, 98.7, 27.3, and 96.1 %, respectively, for conventional CT. Combined FDG PET-CT did not improve the diagnostic accuracy of conventional CT for the detection of LN metastasis in bladder cancer patients scheduled for RC.


Altered gene expression in dry age-related macular degeneration suggests early loss of choroidal endothelial cells.
Age-related macular degeneration (AMD) is a major cause of blindness in developed countries. The molecular pathogenesis of early events in AMD is poorly understood. We investigated differential gene expression in samples of human retinal pigment epithelium (RPE) and choroid from early AMD and control maculas with exon-based arrays. Gene expression levels in nine human donor eyes with early AMD and nine control human donor eyes were assessed using Affymetrix Human Exon ST 1.0 arrays. Two controls did not pass quality control and were removed. Differentially expressed genes were annotated using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and gene set enrichment analysis (GSEA) was performed on RPE-specific and endothelium-associated gene sets. The complement factor H (CFH) genotype was also assessed, and differential expression was analyzed regarding high AMD risk (YH/HH) and low AMD risk (YY) genotypes. Seventy-five genes were identified as differentially expressed (raw p value <0.01; ≥50% fold change, mean log2 expression level in AMD or control ≥ median of all average gene expression values); however, no genes were significant (adj. p value <0.01) after correction for multiple hypothesis testing. Of 52 genes with decreased expression in AMD (fold change <0.5; raw p value <0.01), 18 genes were identified by DAVID analysis as associated with vision or neurologic processes. The GSEA of the RPE-associated and endothelium-associated genes revealed a significant decrease in genes typically expressed by endothelial cells in the early AMD group compared to controls, consistent with previous histologic and proteomic studies. Analysis of the CFH genotype indicated decreased expression of ADAMTS9 in eyes with high-risk genotypes (fold change = -2.61; raw p value=0.0008). GSEA results suggest that RPE transcripts are preserved or elevated in early AMD, concomitant with loss of endothelial cell marker expression. These results are consistent with the notion that choroidal endothelial cell dropout or dedifferentiation occurs early in the pathogenesis of AMD.


TM4SF5-Mediated Roles in the Development of Fibrotic Phenotypes.
Transmembrane 4 L six family member 5 (TM4SF5) can form tetraspanin-enriched microdomains (TERMs) on the cell's surface. TERMs contain protein-protein complexes comprised of tetraspanins, growth factor receptors, and integrins. These complexes regulate communication between extracellular and intracellular spaces to control diverse cellular functions. TM4SF5 influences the epithelial-mesenchymal transition (EMT), aberrant multilayer cellular growth, drug resistance, enhanced migration and invasion, circulation through the bloodstream, tumor-initiation property, metastasis, and muscle development in zebrafish. Here, current data on TM4SF5's roles in the development of fibrotic phenotypes are reviewed. TM4SF5 is induced by transforming growth factor β1 (TGFβ1) signaling via a collaboration with epidermal growth factor receptor (EGFR) activation. TM4SF5, by itself or in concert with other receptors, transduces signals intracellularly. In hepatocytes, TM4SF5 expression regulates cell cycle progression, migration, and expression of extracellular matrix components. In CCl4-treated mice, TM4SF5, α-smooth muscle actin (α-SMA), and collagen I expression are observed together along the fibrotic septa regions of the liver. These fibrotic phenotypes are diminished by anti-TM4SF5 reagents, such as a specific small compound [TSAHC, 4'-(p-toluenesulfonylamido)-4-hydroxychalcone] or a chimeric antibody. This review discusses the antifibrotic strategies that target TM4SF5 and its associated protein networks that regulate the intracellular signaling necessary for fibrotic functions of hepatocytes.


Dynamics of human prothymocytes and xenogeneic thymopoiesis in hematopoietic stem cell-engrafted nonobese diabetic-SCID/IL-2rγnull mice.
To model the developmental pattern of human prothymocytes and thymopoiesis, we used NOD-scid/γc(-/-) mice grafted with human umbilical cord blood CD34(+) hematopoietic progenitor cells (HPCs). Human prothymocytes developed in the murine bone marrow (BM) from multipotent CD34(++)CD38(lo)lineage(-) HPCs to CD34(++)CD7(+)CD2(-) pro-T1 cells that progressed in a Notch-dependent manner to CD34(+)CD7(++)CD2(+) pro-T2 cells, which migrated to the thymus. BM prothymocyte numbers peaked 1 mo after graft, dropped at mo 2, and persisted at low levels thereafter, with only a few CD34(+)CD7(lo) prothymocytes with limited T potential being detected by mo 5. As a consequence, thymopoiesis in this xenogeneic setting began by weeks 4-6, peaked at mo 3, and decreased thenceforth. Analyzing mice grafted at 2, 4 or 8, mo of age showed that in an "older" BM, prothymocyte differentiation was perturbed and resulted in CD34(+)CD7(lo) prothymocytes with limited T potential. Whereas the early drop in BM thymopoietic activity was related to a Notch-independent loss of T potential by CD34(++)CD38(lo)lineage(-) HPCs, the later age-dependent production decline of prothymocytes was linked to a more complex mix of cell-intrinsic and microenvironmental defects. Accordingly, and contrasting with what was observed with umbilical cord blood HPCs, CD34(+) HPCs from human adult BM displayed only marginal thymopoietic activity when grafted into young 2-mo-old NOD-scid/γc(-/-) mice. These data demonstrate that the developmental pattern of BM prothymocytes during human late fetal and early postnatal life can be reproduced in humanized mice, and they suggest that onset of human thymus involution relates to decreased colonization by prothymocytes.


Genome-wide CRISPR activation screen identifies candidate receptors for SARS-CoV-2 entry.
The outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has created a global health crisis. SARS-CoV-2 infects varieties of tissues where the known receptor ACE2 is low or almost absent, suggesting the existence of alternative viral entry pathways. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection. Beyond known host proteins, i.e., ACE2, TMPRSS2, and NRP1, we identified multiple host components, among which LDLRAD3, TMEM30A, and CLEC4G were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spike's N-terminal domain (NTD). Their essential and physiological roles have been confirmed in either neuron or liver cells. In particular, LDLRAD3 and CLEC4G mediate SARS-CoV-2 entry and infection in an ACE2-independent fashion. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of COVID-19 countermeasures.


Tension pneumocephalus after posterior fossa craniotomy: report of four additional cases and review of postoperative pneumocephalus.
Four cases of tension pneumocephalus after either posterior fossa craniotomy or translabyrinthine resection of acoustic neuroma with or without nitrous oxide anesthesia are described. Three of the operations were performed with the patient in the sitting position, and one was done with the patient in the lateral position. Of the three cases operated in the sitting position, no nitrous oxide was used at any time during anesthesia in one. Two patients failed to regain consciousness after the termination of anesthesia, and the other two developed the sudden onset of neurological symptoms 1 to 1.5 hours after the operation. In all cases computed tomography disclosed a large subdural collection of air. Re-exploration of the surgical wound or twist drill aspiration of the subdural air resulted in prompt recovery of neurological status in three patients, whereas the other patient's neurological status improved gradually without any specific treatment. The role played by nitrous oxide, the mechanisms by which air enters the intracranial space, the contributory factors, and the predisposing surgical conditions of tension pneumocephalus are reviewed and discussed. Dependent drainage of the cerebrospinal fluid, especially in a patient with coexisting hydrocephalus, seems to be the most important factor for the development of this complication.


Altered cardiovascular reflex responses during positive pressure breathing.
Cardiovascular responses during hyperinflation produced by positive end-expiratory pressure (PEEP) are considered to be reflexly influenced by pulmonary mechanoreceptors. Numerous studies have indicated heart and vascular effects attributed to mechanical events and cardiopulmonary mechanoreflexes. Yet interactions of these modalities with the systemic baroreflexes are not clear. We examined aspects of these modulatory interactions by distinguishing changes in pulmonary, heart, and vascular responses during PEEP-hyperinflation before and after progressive elimination of chemo-, mechano-, and baroreflex influences in the closed-chest anesthetized rabbit. During respiratory alkalosis PEEP was imposed in increments of 2.5 cm H2O (range 0.0 to 7.5 cm H2O) before and during control of carotid intrasinus pressure and following aortic denervation and vagotomy. Heart rate responses during PEEP increased prior to aortic denervation, decreased following elimination of baroreflexes, and were abolished after vagotomy. The fall in mean arterial pressure (MAP) during PEEP was accentuated during elimination of the baroreflexes and ameliorated following vagotomy. Mean right atrial (MRAP), intrapleural (MIP), and right atrial transmural pressure increased during PEEP prior to vagotomy. Regression analyses of MAP versus MRAP and MAP versus MIP suggest that vagally receptors reflexly influence venous as well as systemic arterial vascular pressure. Conclusion indicate that when superimposed on mechanical events, cardiopulmonary mechanoreceptors and arterial baroreceptors effect conflicting facilitory reflex influences on heart and vascular responses during PEEP-hyperinflation.


Contrasting trends in light pollution across Europe based on satellite observed night time lights.
Since the 1970s nighttime satellite images of the Earth from space have provided a striking illustration of the extent of artificial light. Meanwhile, growing awareness of adverse impacts of artificial light at night on scientific astronomy, human health, ecological processes and aesthetic enjoyment of the night sky has led to recognition of light pollution as a significant global environmental issue. Links between economic activity, population growth and artificial light are well documented in rapidly developing regions. Applying a novel method to analysis of satellite images of European nighttime lights over 15 years, we show that while the continental trend is towards increasing brightness, some economically developed regions show more complex patterns with large areas decreasing in observed brightness over this period. This highlights that opportunities exist to constrain and even reduce the environmental impact of artificial light pollution while delivering cost and energy-saving benefits.


Delayed severe extrapyramidal disturbance following frequent depot phenothiazine administration.
The authors report the occurrence of a sever striopallidal disorder in a schizophrenic patient one week after he received fluphenazine enanthate injections on an every-other-day schedule. In view of current interest in depot psychopharmaceuticals, they recommend that careful attention be given to dosage and administration schedules and to the possibility of delayed pseudoparkinsonian symptoms. Emergency room physicians should be alerted to the possible side effects of such drugs.


Acute transverse myelitis - A rare clinical manifestation of Lyme neuroborreliosis.
Acute transverse myelitis (ATM) is a rare, potentially devastating neurological syndrome that has variety of causes, infectious being one of them. Lyme disease (LD) is the most common vector borne zoonosis in the United States (U.S.). While neurologic complications of LD are common, acute transverse myelitis is an exceedingly rare complication. We present a case of a previously healthy 25-year-old man who presented with secondary erythema migrans, aseptic meningitis and clinical features of transverse myelitis including bilateral lower extremity motor and sensory deficits manifesting as weakness and numbness, urinary retention and constipation. Despite negative serum antibodies against Borrelia burgdoferi, cerebrospinal fluid (CSF) was positive for Borrelia burgdorferi PCR. Following treatment with methylprednisolone and ceftriaxone, he attained complete recovery apart from neurogenic bladder necessitating intermittent self-catheterization. We report rare manifestation of a common disease and emphasize the importance of considering LD in the differential diagnosis of acute transverse myelitis, particularly in residents of endemic areas.


Understanding the Medical Dictionary for Regulatory Activities (MedDRA) reporting of herpes simplex virus (HSV) adverse events in atopic dermatitis clinical trials.
Drug efficacy is best evaluated by randomized, controlled, double-blind clinical trials; however, safety is harder to assess. The Medical Dictionary for Regulatory Activities (MedDRA) is used to track and categorize adverse events (AE) during clinical trials. Recent atopic dermatitis (AD) clinical trials were reviewed to illustrate how an understanding of MedDRA may be helpful when evaluating the rates and nature of adverse events related to herpes simplex virus (HSV) infection. All completed AD clinical trials (excluding phase I studies) with results on clinicaltrials.gov (01/01/2018-01/31/2023) were queried in January 2023. MedDRA version, preferred term (PT) for AEs captured as "HSV", PTs for other AEs possibly related to HSV, frequency thresholds for reporting non-serious AEs, and route of treatment were recorded. Of the 46 clinical trials, 17 had PTs for AEs captured as "HSV". Among all studies, 11 different versions of MedDRA were utilized, from versions 10 to 24.1. In all studies, PTs for AEs captured as "HSV" were listed in the Infections and Infestations system organ class (SOC) classification of MedDRA. PTs varied from "herpes simplex", "herpes virus infection", "herpes ophthalmic", "ophthalmic herpes simplex", "nasal herpes", "oral herpes", "herpes dermatitis", "eczema herpeticum", "genital herpes simplex", and "genital herpes." While one clinical trial of dupilumab (NCT03359356) simply reported the PT "oral herpes" as an AE, a clinical trial of DS107 (NCT03817190) reported the PTs "oral herpes", "herpes simplex", and "herpes virus infection" separately. In the DS107 clinical trial, it is unclear if the same adverse event was reported under multiple PTs or if multiple HSV-related AEs occurred. Although the definition of HSV is unchanged from 2018 to 2023 and there are few changes between MedDRA versions, coding for HSV is complex. HSV events can be reported in different ways, which may impact the interpretation of a drug's safety profile.


An accidental laboratory exposure to Brucella melitensis: the prospective post-exposure management and a detailed investigation into the nature of the exposure.
Our aim was to prospectively manage 22 Brucella-exposed individuals and identify the lapses in laboratory practices that lead to the exposure. The exposed individuals were risk-stratified, assessed for post-exposure prophylaxis (PEP), counselled to self-monitor symptoms and followed-up with three serology tests. Staff laboratory practices were recorded. Ten out of 13 high-risk individuals received PEP within 48 h of exposure. Compliance with PEP and serology monitoring was 90 and 96 %, respectively. No brucellosis cases were documented. A single handler manipulated the Brucella isolate on the open bench. Movement of the isolate was tracked in detail, highlighting various points of laboratory non-conformance. Early PEP intervention is effective in preventing acquired brucellosis. Our pragmatic post-exposure management achieved high PEP and serology compliance. We experience first-hand how regular staff engagement motivated PEP adherence and interval blood sampling attendance. The enforcement of practical strategies and safety practices was also implemented without compromising our laboratory processing times.


Return to Sport-Specific Performance After Primary Anterior Cruciate Ligament Reconstruction: A Systematic Review.
Physicians counseling athletes on the prognosis of sport-specific performance outcomes after anterior cruciate ligament reconstruction (ACLR) depend on the published literature. However, critical appraisal of the validity and biases in these studies is required to understand how ACLR affects an athlete's ability to return to sport, the athlete's sport-specific performance, and his or her ability to achieve preinjury levels of performance. This review identifies the published prognostic studies evaluating sport-specific performance outcomes after ACLR. A risk of bias assessment and summaries of return to sport and career longevity results are provided for each included study. Systematic review. Electronic databases (Ovid MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and PUBMED) were searched via a defined search strategy with no limits, to identify relevant studies for inclusion in the review. A priori defined eligibility criteria included studies measuring sport-specific performance within an athlete's sport, before and after primary ACLR. Reference lists of eligible studies were hand-searched for additional relevant studies. Data extraction was performed by use of a standardized spreadsheet. Each included study was assessed by use of 6 bias domains of the Quality in Prognosis Studies tool to critically appraise study participation, study attrition, prognostic factors, outcome measurement, confounders, and statistical analysis and reporting. Two authors independently performed each stage of the review and reached consensus through discussion. Fifteen pertinent prognostic studies evaluated sport-specific performance outcomes and/or return to play after ACLR for athletes participating in competitive soccer, football, ice hockey, basketball, Alpine ski, X-Games ski and snowboarding, and baseball. Twelve of these studies were considered to have a high level of bias. This review demonstrated that most high-performance or professional athletes returned to their preinjury level of sport after ACLR. The bulk of evidence suggests there was a measurable decrease in performance statistics, although this is highly sport-specific. A paucity of literature is available that addresses sport-specific performance in athletes after ACLR. This review has determined that the available literature is highly biased and must be read with caution. By better understanding the validity and biases in the published literature, physicians can provide more informed prognoses about return to sport-specific performance after ACLR while considering risk factors relevant to their patients. CRD42016046709 (International Prospective Register of Systematic Reviews, https://www.crd.york.ac.uk/prospero/ ).


[Assessment of adaptation risk in the individual prenosological control].
Trends in the development of modern ideas about health as the ability to adapt require personalization and preventive orientation in evaluating and predicting individual health. It can be realized only on the basis ofprenosological approach, which is necessary in medicine and physiology of labor, in particular--in the aviation and space medicine. The article analyzes the concept of adaptation risks and its application for health, assessing on the basis of the results of space and Earth modeling studies of autonomic regulation according to the HRV (heart rate variability) analysis. It is demonstrated that the developed methods for individual prenosological control have high diagnostic efficiency.


[Hydrogenase activity in Thiocapsa roseopersicina according to the D2--H20 metabolic reaction].
Extracts of Thiocapsa roseopersicina cells show hydrogenase activity, measured by evolution of H2 from reduced methylviologene (MV) and by D2-H2O exchange reaction. According to these reactions the most part of hydrogenases is found to be in the soluble fraction. Hydrogenase activity measured in the exchange reaction is completely inhibited by p-chloromercurybenzoate (5-10- minus 3 M), iodacetate (1-10- minus 2 M) and 26% inhibited by KCN and o-phenanthroline (5-10- minus 3 M). Evolution of H2 from reduced MV was not inhibited by o-phenanthroline, KCN and iodacetate and was inhibited by 66% only with p-chloromercurybenzoate. Light and ATP stimulated hydrogenase activity of chromatophores did not affect on its activity in the soluble fraction. The results obtained show that there are certain differences in hydrogenase systems responsible for the exchange reaction and evolution of H2.


Control of thrombopoietin-induced megakaryocytic differentiation by the mitogen-activated protein kinase pathway.
Thrombopoietin (TPO) is the major regulator of both growth and differentiation of megakaryocytes. We previously showed that both functions can be generated by TPO in the megakaryoblastic cell line UT7, in which murine Mpl was introduced, and are independently controlled by distinct regions of the cytoplasmic domain of Mpl. Particularly, residues 71 to 94 of this domain (deleted in the mutant mpl delta3) were found to be required for megakaryocytic maturation but dispensable for proliferation. We show here that TPO-induced differentiation in UT7 cells is tightly dependent on a strong, long-lasting activation of the mitogen-activated protein kinase (MAPK) pathway. Indeed, (i) in UT7-mpl cells, TPO induced a strong activation of extracellular signal-regulated kinases (ERK) which was persistent until at least 4 days in TPO-containing medium; (ii) a specific MAPK kinase (MEK) inhibitor inhibited TPO-induced megakaryocytic gene expression; (iii) the Mpl mutant mpl delta3, which displayed no maturation activity, transduced only a weak and transient ERK activation in UT7 cells; and (iv) TPO-induced megakaryocytic differentiation in UT7-mpl delta3 cells was partially restored by expression of a constitutively activated mutant of MEK. The capacity of TPO to trigger a strong and prolonged MAPK signal depended on the cell in which Mpl was introduced. In BAF3-mpl cells, TPO triggered a weak and transient ERK activation, similar to that induced in UT7-mpl delta3 cells. In these cells, no difference in MAPK activation was found between normal Mpl and mpl delta3. Thus, depending on the cellular context, several distinct regions of the cytoplasmic domain of Mpl and signaling pathways may contribute to generate quantitative variations in MAPK activation.


My home is my castle! Or is it? Hospitalizations following home injury in Israel, 1997-2001.
Although the home is perceived to be a safe haven, it is a scene of numerous injuries. To characterize home injury in Israel, the victims, injury circumstances and outcomes, and to identify groups at high risk for injury in order to focus future interventions and thus effectively prevent these injuries and their associated hospitalizations. We analyzed 5 year records (1997-2001) from the National Trauma Registry of all patients arriving at eight trauma centers following home injury and admitted to hospital, transferred to another medical center, or died in the emergency department. The study group included 26,921 patients, constituting 34% of all unintentional hospitalized trauma patients. Twenty-seven percent were children (0-4 years) and 37% were elderly (> or = 65 years), the two age groups whose home injury accounted for most of the trauma injuries. Among children more boys (59%) than girls (41%) were injured, but the opposite was true for the elderly (30% males and 70% females). The share of females among the home-injured increased with age. Falls caused 79% of all home injuries (97% among the elderly) and bums 9%, increasing to 18% among children (0-4 years). Among non-Jewish home-injured patients, infants predominated (50% compared to 20% among Jews). Moderate to critical injuries amounted for 42%, with 38% of the home-injured and 60% of the elderly requiring surgery. The clinical and economic consequences of home injuries differed according to the type of injury, with bums carrying the heaviest toll of prolonged intensive care and hospital stay. Overall, hospital stay averaged 6.2 days per patient (median 3 days). Falls among the elderly, bums among children, and a high prevalence of hospitalization among non-Jewish children define groups at high risk for home injuries. Prevention programs should be based on these findings and should focus on the more vulnerable groups.


Laparoscopic excision of endometriosis: a randomized, placebo-controlled trial.
To examine the effect on pain and quality of life for women with all stages of endometriosis undergoing laparoscopic surgery compared with placebo surgery. A randomized, blinded, crossover study. A tertiary referral unit in a district general hospital. Thirty-nine women with histologically proven endometriosis completed the 12-month study. Women were randomized to receive initially either a diagnostic procedure (the delayed surgical group) or full excisional surgery (the immediate surgery group). After 6 months, repeat laparoscopy was performed, with removal of any pathology present. The end points were changes from baseline values of visual analogue pain scores, validated quality-of-life instruments (EQ-5D and SF-12), and sexual activity questionnaire scores. Patients and assessors of outcomes were blinded to the treatment-group assignment. Significantly more of the 39 women operated on according to protocol reported symptomatic improvement after excisional surgery than after placebo: 16 of 20 (80%) vs. 6 of 19 (32%); chi(2)(1) = 9.3. Other aspects of quality of life were also significantly improved 6 months after excisional surgery but not after placebo. Progression of disease at second surgery was demonstrated for women having only an initial diagnostic procedure in 45% of cases, with disease remaining static in 33% and improving in 22% of cases. Nonresponsiveness to surgery was reported in 20% of cases. Laparoscopic excision of endometriosis is more effective than placebo at reducing pain and improving quality of life. Surgery is associated with a 30% placebo response rate that is not dependent on severity of disease. Approximately 20% of women do not report an improvement after surgery for endometriosis.


Effects of general principles of person transfer techniques on low back joint extension moment.
The purpose of this study was to examine the effects of general principles of person transfer techniques specifically on the low back joint extension moment. These effects were examined by the following measurable quantitative parameters: 1) trunk bending angle, 2) knee flexion angle, 3) distance between the centers of gravity (COGs) of the caregiver and patient, representing the distance between the caregiver and patient, and 4) the vertical component of the ground reaction force representing the amount of the weight-bearing load on the caregiver's low back during transfers with and without assistive devices. Twenty students each took the role of caregiver, and one healthy adult simulated a patient. The participants performed three different transfer tasks: without any assistive device, with the patient wearing a low back belt, and with the caregiver using a transfer board. We found that the distance between the COGs and the vertical component of the ground reaction force, but not the trunk bending and knee flexion angles, were the variables that affected the low back joint extension moment. Our results suggest that the general principle of decreasing the distance between COGs is most effective for decreasing the low back joint extension moment during transfers under all conditions.


The use of induced pluripotent stem cells to reveal pathogenic gene mutations and explore treatments for retinitis pigmentosa.
Retinitis pigmentosa (RP) is an inherited human retinal disorder that causes progressive photoreceptor cell loss, leading to severe vision impairment or blindness. However, no effective therapy has been established to date. Although genetic mutations have been identified, the available clinical data are not always sufficient to elucidate the roles of these mutations in disease pathogenesis, a situation that is partially due to differences in genetic backgrounds. We generated induced pluripotent stem cells (iPSCs) from an RP patient carrying a rhodopsin mutation (E181K). Using helper-dependent adenoviral vector (HDAdV) gene transfer, the mutation was corrected in the patient's iPSCs and also introduced into control iPSCs. The cells were then subjected to retinal differentiation; the resulting rod photoreceptor cells were labeled with an Nrl promoter-driven enhanced green fluorescent protein (EGFP)-carrying adenovirus and purified using flow cytometry after 5 weeks of culture. Using this approach, we found a reduced survival rate in the photoreceptor cells with the E181K mutation, which was correlated with the increased expression of endoplasmic reticulum (ER) stress and apoptotic markers. The screening of therapeutic reagents showed that rapamycin, PP242, AICAR, NQDI-1, and salubrinal promoted the survival of the patient's iPSC-derived photoreceptor cells, with a concomitant reduction in markers of ER stress and apoptosis. Additionally, autophagy markers were found to be correlated with ER stress, suggesting that autophagy was reduced by suppressing ER stress-induced apoptotic changes. The use of RP patient-derived iPSCs combined with genome editing provided a versatile cellular system with which to define the roles of genetic mutations in isogenic iPSCs with or without mutation and also provided a system that can be used to explore candidate therapeutic approaches.


Thyrotropin receptor expression in Graves' orbital adipose/connective tissues: potential autoantigen in Graves' ophthalmopathy.
It is acknowledged that the TSH receptor (TSHr) on thyroid follicular cells is the autoantigen involved in the hyperthyroidism of Graves' disease. However, whether this receptor is expressed in extrathyroidal tissues, and whether it participates directly in the pathogenesis of Graves' ophthalmopathy (GO) are unclear. We sought to detect the expression of TSHr messenger ribonucleic acid (mRNA) and protein in orbital adipose/connective tissue specimens and in human orbital preadipocyte fibroblast cultures using liquid hybridization analysis and immunohistochemical methods. We demonstrated intact and variant TSHr mRNA transcripts and TSHr-like immunoreactivity in orbital adipose/connective tissue specimens from patients with GO. In addition, TSHr-like immunoreactivity was detected in early passage GO preadipocyte fibroblast cultures that were shown to include some adipose cells. In contrast, neither TSHr mRNA nor protein was detected in normal orbital adipose/connective tissue specimens or in late passage GO orbital fibroblast cultures containing no lipid-laden adipose cells. In conclusion, we showed that TSHr is expressed in the adipose/connective tissue of the diseased orbit in GO. In addition, TSHr is demonstrable in early passage GO preadipocyte orbital fibroblast cultures that contain a subpopulation of adipocytes. Subsequent passaging of these cells results in the loss of both TSHr expression and adipocyte-specific staining. These results suggest that both the expression of this receptor and the accumulation of adipose tissue in the orbit in GO may be induced in vivo by a humoral factor(s) not present in the cell culture environment.


A framework for assessing the effectiveness of antihunger advocacy organizations.
Food insufficiency is a major public health problem that has been linked to poor nutritional intake, poor diabetes management, poor cognitive development in children, and other adverse health outcomes. Since the 1960s, antihunger advocacy organizations (AHAOs) have fought to alleviate hunger at the local, state, and federal levels. Few studies have investigated the organizational structure, programs, advocacy activities, and outcomes of these organizations, although many organizations have been instrumental in advocating for state and federal food policy, creating measurements for hunger, and conducting research. Four state-level AHAOs were studied by using multiple case study methodology and grounded theory for analysis to assess organizational effectiveness. The findings highlight a conceptual framework that identified 19 important organizational characteristics that reflect organizational capacity, performance, achievement, and effectiveness. The conceptual framework may be useful in assessing effectiveness of public health organizations and coalitions.


Binding of Escherichia coli heat-stable enterotoxin and rise of cyclic GMP in COLO 205 human colonic carcinoma cells.
Escherichia coli heat-stable enterotoxin (STa) was found to bind on the surface of human colonic (COLO 205) cells. The binding of [125I]STa to cell membranes was found to be specific, reversible and saturable. Scatchard analysis of the equilibrium binding demonstrated a single class of binding sites with a Kd of 0.5 x 10(-10) M. Autoradiographic analysis of polyacrylamide gel electrophoresis revealed the specific incorporation of [125I]STa into a single STa binding protein with a molecular mass of 95 kDa. Following incubation of COLO 205 cells with STa, a rise of intracellular cGMP was also evident.


A Multidimensional Approach to Characterizing Psychosocial Health During Pregnancy.
Objectives Domains of psychosocial health have been separately connected to pregnancy outcomes. This study explores the relationship between five domains of psychosocial health and their joint association with prenatal health and pregnancy outcomes. Methods Women from a prospective cohort study in Durham, North Carolina were clustered based on measures of paternal support, perceived stress, social support, depression, and self-efficacy. Clusters were constructed using the K-means algorithm. We examined associations between psychosocial health and maternal health correlates, pregnancy intention, and pregnancy outcomes using Chi square tests and multivariable models. Results Three psychosocial health profiles were identified, with the first (Resilient; n = 509) characterized by low depression and perceived stress and high interpersonal support, paternal support, and self-efficacy. The second profile (Vulnerable; n = 278) was marked by high depression and perceived stress, and low interpersonal support, paternal support, and self-efficacy. The third profile (Moderate, n = 526) fell between the other profiles on all domains. Health correlates, pregnancy intention, and pregnancy outcomes varied significantly across profiles. Women with the vulnerable profile were more likely to have risky health correlates, have an unintended pregnancy, and deliver preterm. Women with the resilient profile had better birth outcomes and fewer deleterious health correlates, preconception and prenatally. Conclusions We posit that vulnerable psychosocial health, deleterious health correlates, and the stress which often accompanies pregnancy may interact to magnify risk during pregnancy. Identifying and intervening with women experiencing vulnerable psychosocial health may improve outcomes for women and their children.


Effects of dexamethasone, corticosterone, and ACTH on lordosis in ovariectomized and adrenalectomized-ovariectomized rats.
The involvement of the pituitary-adrenocortical axis in the control of the lordosis reflex was investigated; In Experiment 1, estrogen-primed ovariectomized (ovx) and adrenalectomized-ovariectomized (adx-ovx) females were treated chronically with dexamethasone, a compound blocking ACTH release from the pituitary. Dexamethasone inhibited lordosis, effectively blocking an adrenalectomy-induced facilitation of the reflex. In Experiment 2, corticosterone was similarly administered chronically; this compound also inhibited lordosis in adx-ovx females. In Experiment 3, acute peripheral administration of synthetic ACTH caused a marked increase in lordosis in ovx females. The results suggest that in the adrenally intact animal, ACTH may exert its effect through adrenal steroids. An acute elevation of adrenal steroids may increase lordosis, whereas a chronic elevation may decrease it.


Laser-Pulse-Length Effects in Ultrafast Laser Desorption.
Shortening the laser pulse length opens up new opportunities for laser desorption (LD) of molecules, with benefits for mass spectrometry (MS) sampling and ionization. The capability to ablate any material without the need for an absorbing matrix and the decrease of thermal damage and molecular fragmentation has promoted various applications with very different parameters and postionization techniques. However, the key issues of the optimum laser pulse length and intensity to achieve efficient and gentle desorption of molecules for postionization in MS are not resolved, although these parameters determine the costs and complexity of the required laser system. Here, we address this research gap with a systematic study on the effect of the pulse length on the LD of molecules. Keeping all other optical and ionization parameters constant, we directly compared the pulses in the femtosecond, picosecond, and nanosecond range with respect to LD-induced fragmentation and desorption efficiency. To represent real-world applications, we investigated the LD of over-the-counter medicaments naproxen and ibuprofen directly from tablets as well as the LD of retene and ship emission aerosols from a quartz filter. With our study design, we excluded interfering effects on fragmentation and LD efficiency from, for example, collisional cooling or postionization by performing the experiments in vacuum with resonance-enhanced multiphoton ionization as the postionization technique. Regarding LD-induced fragmentation, we already found benefits for the picosecond pulses. However, the efficiency of LD was found to continuously increase with decreasing pulse length, pointing to the application potential of ultrashort pulses in trace analytics. Because many interfering effects beyond the LD pulse length could be excluded in the experiment, our results may be directly transferable to the LD applied in other techniques.