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Objective: The New York City Mental Health Care Monitoring Initiative uses Medicaid claims data to identify individuals with serious mental illness who are experiencing or at risk for gaps in services. In this study the authors assessed whether proposed service use algorithms accurately identified such individuals.Methods: A random sample of 500 individuals with serious mental illness was identified. Individuals belonged to specific high-need cohorts and met predefined claims-based criteria for potential service gaps. Clinical staff initiated reviews with prior service providers for 230 individuals.Results: Over a two-week period staff completed reviews for 188 cases (88%). In 66 cases (35%) the individual was fully engaged in care; 84 (45%) had a recent episode of disengagement that was appropriately addressed, and 38 (20%) were not receiving adequate services.Conclusions: The proposed service use algorithms successfully identified high-need individuals with serious mental illness at risk for gaps in services. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the preparation of human service organizations for the minimization of risk and the maximization of opportunity. Three primary areas were examined: political connectivity (which aids in the maximization of opportunity), documentation of agency policies (which aids in the minimization of risk), and comprehensive strategic planning (which aids in both the maximization of opportunity and the minimization of risk). A survey of organizational characteristics was conducted with agencies known for provision of sexual education services to adolescents within Florida. This study revealed some of the strengths and deficits of the organizations in the sample. Strengths included fairly high rates of political connectivity and written documentation of personnel policies. There were deficits in the documentation of programmatic policies and the comprehensiveness of strategic plans. [ABSTRACT FROM AUTHOR]

Ninety-three parents and 102 adolescents were referred by juvenile court and treated for substance abuse and a co-morbid diagnosis of either oppositional defiant or conduct disorder using a parent education program over a six-week period. The goals of this study were to assess whether or not active parent involvement and the concurrent treatment of severe behavior problems would reduce teen substance as measured by the adolescent SASSI scale. In addition, if the SASSI scale indicated a significant reduction in substance abuse would these changes be maintained after a 12-month follow-up period as measured by re-arrest rates through juvenile court records? The results indicated that a parent's participation in their teen's treatment of substance abuse and other severe behavioral problems did have a major positive impact. Even though the adolescent's attitudes and defensiveness towards drugs or alcohol did not significantly change their substance abuse did. This was demonstrated by both the statistically significant changes on the adolescent's SASSI scores and the fact that 85% did not relapse over the course of an entire year after treatment was completed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Several small-N, uncontrolled reports have demonstrated that the behavioral technique of attention shaping has significantly increased attention span among severely ill schizophrenia patients. METHOD: In this study, we evaluated the effectiveness of using an individually administered intervention for improving sustained attention, Attention Process Training (APT), followed by an attention-shaping procedure within the context of an ongoing skills training group. Patients were randomly assigned to receive either the APT and attention-shaping sequence (n = 18) or equivalent hours of treatment in the same intensive behavioral rehabilitation program (n = 13). RESULTS: Results indicated dramatic improvements in attentiveness in the cognitive rehabilitation condition compared with the control condition, which demonstrated essentially no change in attentiveness over the 12 weeks of treatment. The attention-shaping intervention appeared to account for the majority of the effect. In contrast to the observational data, performance on neuropsychological tests was unaffected by the cognitive interventions. CONCLUSIONS: This two-phase intervention demonstrated effectiveness in promoting attentive behavior among chronic schizophrenia patients with severe attentional impairment. [ABSTRACT FROM AUTHOR]

The purpose of this article is to identify, assess, and offer solutions to common measurement errors found in sexual abstinence education evaluation. A critical review of the methodology of adolescent sexuality research was performed. "Gold standards" of their measurement strategy were derived and applied against 14 selected studies. Many of the articles reviewed had substantial limitations in their measurement strategies. However, several articles demonstrated excellence and serve as models for future efforts. Sexual abstinence education evaluation is plagued by the inherent weaknesses of self-report and health outcome measures. However, with careful adherence to the gold standards proposed, it is possible to limit the threat from these weaknesses, maximizing the benefit of self-report surveys and county-level health indicators. [ABSTRACT FROM AUTHOR]

The development of anticonvulsant drugs is an example of where advances in basic neuroscience have improved patient care. Potential benefits also spill over to nonepileptic patients, especially those with chronic pain. It is increasingly recognized that there are many similarities between the molecular pathophysiology of epileptogenesis and that of chronic pain. Anticonvulsant drugs are now used extensively for treating neuropathic and non-neuropathic pain syndromes. This article summarizes the presumed modes of action of commonly used anticonvulsant drugs and points out where they may be important for treating pain. The clinical evidence for their efficacy is examined. In addition, some anticonvulsant drugs that are under development are assessed and those that may be effective for treating pain are highlighted. [ABSTRACT FROM AUTHOR]

In this study, we investigated the ethical decision making of 30 individual and 30 family therapists in order to detect the types of decision making used by practicing therapists. Informants responded to three ethical dilemmas. Two of the situations were hypothetical. The third dilemma was a situation the informant had experienced in practice. Each interview was assessed for decision-making style, using content analysis. Kohlberg's justice reasoning and Gilligan's care reasoning provided the conceptual foundations for this analysis. The results suggest that both family and individual therapists prefer care reasoning on all dilemma types. There was significantly more care reasoning demonstrated on the personal dilemma than on the hypothetical dilemmas. Characteristics of informants did not provide clear explanations for the differences found in reasoning. [ABSTRACT FROM AUTHOR]

In developing a rehabilitation plan for clients with severe mental illnesses, several questions arise including which skill areas to target for rehabilitation and when to utilize specific rehabilitation strategies. The Rehabilitation Readiness Determination Profile (RRDP) is a new expressed needs interview designed to answer these questions. This study reports reliability and validity data on the RRDP. Twenty-five individuals with schizophrenia or schizoaffective disorder were administered the RRDP intervew, and also received ratings of symptoms and attendance at rehabilitations groups. Interrater reliability was documented for RRDP ratings. Readiness ratings were partially influenced by symptoms (mainly negative symptoms), but did predict rahabilitation group attendance independent of symptoms. The data support the reliability and validity of a new interview for assessing rehabilitation needs. [ABSTRACT FROM AUTHOR]

In a study of the validity of a new interview for assessing rehabilitation readiness, 25 clients with schizophrenia or schizoaffective disorder were administered the new interview, and also received ratings of positive, negative, and disorganized symptoms. Separate regression analyses were calculated to determine the effects of symptoms on each of the three dimensions of rehabilitation functioning: readiness for rehabilitation, participation in rehabilitation group treatments, and global functioning. Negative symptoms were associated with ratings of readiness, while disorganized symptoms influenced participation, and positive symptoms had the strongest influence on global functioning. The results suggest that symptoms exert a differential effect on the rehabilitation process, and that further research is needed to clarify the subtle relationships between illness and functioning in rehabilitation programs. [ABSTRACT FROM AUTHOR]

FOR DEVELOPERS YOU ARE NOT ALONE Who listens to the bartender's problems? As a developer, you may answer questions and solve problems for any number of computer users. But where […]

Abstract Background The inherent toxicity of unmodified Quantum Dots (QDs) is a major hindrance to their use in biological applications. To make them more potent as neuroprosthetic and neurotherapeutic agents, thioglycolic acid (TGA) capped CdTe QDs, were coated with a gelatine layer and investigated in this study with differentiated pheochromocytoma 12 (PC12) cells. The QD - cell interactions were investigated after incubation periods of up to 17 days by MTT and APOTOX-Glo Triplex assays along with using confocal microscopy. Results Long term exposure (up to 17 days) to gelatinated TGA-capped CdTe QDs of PC12 cells in the course of differentiation and after neurites were grown resulted in dramatically reduced cytotoxicity compared to non-gelatinated TGA-capped CdTe QDs. Conclusion The toxicity mechanism of QDs was identified as caspase-mediated apoptosis as a result of cadmium leaking from the core of QDs. It was therefore concluded that the gelatine capping on the surface of QDs acts as a barrier towards the leaking of toxic ions from the core QDs in the long term (up to 17 days).

Abstract Background Ghrelin is a 28-amino acid octanolyated peptide, synthesised primarily in the stomach. It stimulates growth hormone release, food intake and exhibits many other diverse effects. Our group have previously determined that ghrelin inhibited human contractility in vitro. The aim of this study therefore, was to investigate the expression of ghrelin, its receptor, the growth hormone secretagogue receptor type 1 (GHS-R1), ghrelin O-acyltransferase (GOAT) which catalyses ghrelin octanoylation, prohormone convertase 1/3 (PC1/3) responsible for pro-ghrelin processing, in human myometrium, during pregnancy prior to labour, during labour and in the non-pregnant state. Modulation of ghrelin and ghrelin receptor expression in cultured myometrial cells was also investigated. Methods mRNA and protein were isolated from human myometrium and the myometrial smooth muscle cell line hTERT-HM; and real-time fluorescence RT-PCR, western blotting and fluorescence microscopy performed. The effects of β-Estradiol and bacterial lipopolysaccharide (LPS) on hTERT-HM gene expression were evaluated by western blotting. Results We have reported for the first time the expression and processing of ghrelin, GHS-R1, GOAT and PC1/3 expression in human myometrium, and also the down-regulation of ghrelin mRNA and protein expression during labour. Furthermore, GHS-R1 protein expression significantly decreased at labour. Myometrial GOAT expression significantly increased during term non-labouring pregnancy in comparison to both non-pregnant and labouring myometrium. Mature PC1/3 protein expression was significantly decreased at term pregnancy and labour in comparison to non-pregnant myometrium. Ghrelin, GHS-R1, GOAT and PC1/3 mRNA and protein expression was also detected in the hTERT-HM cells. Ghrelin protein expression decreased upon LPS treatment in these cells while β-Estradiol treatment increased GHS-R1 expression. Conclusions Ghrelin processing occurred in the human myometrium at term pregnancy and in the non-pregnant state. GOAT expression which increased during term non-labouring pregnancy demonstrating a similar expression pattern to prepro-ghrelin and GHS-R1, decreased at labour, signifying possible myometrial ghrelin acylation. Moreover, the presence of PC1/3 may contribute to pro-ghrelin processing. These results along with the previous in vitro data suggest that myometrially-produced and processed ghrelin plays a significant autocrine or paracrine role in the maintenance of relaxation in this tissue during pregnancy. Furthermore, the significant uterine modulators LPS and β-Estradiol are involved in the regulation of ghrelin and ghrelin receptor expression respectively, in the human myometrium.

Abstract Background This paper is an attempt to trace the evolution of the ribosome through the evolution of the universal P-loop GTPases that are involved with the ribosome in translation and with the attachment of the ribosome to the membrane. The GTPases involved in translation in Bacteria/Archaea are the elongation factors EFTu/EF1, the initiation factors IF2/aeIF5b + aeIF2, and the elongation factors EFG/EF2. All of these GTPases also contain the OB fold also found in the non GTPase IF1 involved in initiation. The GTPase involved in the signal recognition particle in most Bacteria and Archaea is SRP54. Results 1) The Elongation Factors of the Archaea based on structural considerations of the domains have the following evolutionary path: EF1→ aeIF2 → EF2. The evolution of the aeIF5b was a later event; 2) the Elongation Factors of the Bacteria based on the topological considerations of the GTPase domain have a similar evolutionary path: EFTu→ IF→2→EFG. These evolutionary sequences reflect the evolution of the LSU followed by the SSU to form the ribosome; 3) the OB-fold IF1 is a mimic of an ancient tRNA minihelix. Conclusion The evolution of translational GTPases of both the Archaea and Bacteria point to the evolution of the ribosome. The elongation factors, EFTu/EF1, began as a Ras-like GTPase bringing the activated minihelix tRNA to the Large Subunit Unit. The initiation factors and elongation factor would then have evolved from the EFTu/EF1 as the small subunit was added to the evolving ribosome. The SRP has an SRP54 GTPase and a specific RNA fold in its RNA component similar to the PTC. We consider the SRP to be a remnant of an ancient form of an LSU bound to a membrane. Reviewers This article was reviewed by George Fox, Leonid Mirny and Chris Sander.

Abstract Background The male Atlantic salmon generally matures in fresh water upon returning after one or several years at sea. Some fast-growing male parr develop an alternative life strategy where they sexually mature before migrating to the oceans. These so called 'precocious' parr or 'sneakers' can successfully fertilise adult female eggs and so perpetuate their line. We have used a custom-built cDNA microarray to investigate gene expression changes occurring in the salmon gonad and brain associated with precocious maturation. The microarray has been populated with genes selected specifically for involvement in sexual maturation (precocious and adult) and in the parr-smolt transformation. Results Immature and mature parr collected from a hatchery-reared stock in January were significantly different in weight, length and condition factor. Changes in brain expression were small - never more than 2-fold on the microarray, and down-regulation of genes was much more pronounced than up-regulation. Significantly changing genes included isotocin, vasotocin, cathepsin D, anamorsin and apolipoprotein E. Much greater changes in expression were seen in the testes. Among those genes in the testis with the most significant changes in expression were anti-Mullerian hormone, collagen 1A, and zinc finger protein (Zic1), which were down-regulated in precocity and apolipoproteins E and C-1, lipoprotein lipase and anti-leukoproteinase precursor which were up-regulated in precocity. Expression changes of several genes were confirmed in individual fish by quantitative PCR and several genes (anti-Mullerian hormone, collagen 1A, beta-globin and guanine nucleotide binding protein (G protein) beta polypeptide 2-like 1 (GNB2L1) were also examined in adult maturing testes. Down-regulation of anti-Mullerian hormone was judged to be greater than 160-fold for precocious males and greater than 230-fold for November adult testes in comparison to July testes by this method. For anti-Mullerian hormone and guanine nucleotide binding protein beta polypeptide 2-like 1 expression changes in precocious males mirrored mature adults (November) but for collagen 1A and beta-globin the pattern was more complex. Conclusions Expression changes in the fish brain during the process of precocious sexual maturation were small compared to those in the testes. Microarray analysis suggested down-regulation of housekeeping functions and up-regulation of a small number of specific processes. Transcriptional changes in the testes were much more pronounced with anti-Mullerian hormone playing a major role. Expression profiles for mature parr and maturing adult testes indicate subtle differences in gene expression between these two related groups.

Abstract Background The unique and tuneable photonic properties of Quantum Dots (QDs) have made them potentially useful tools for imaging biological entities. However, QDs though attractive diagnostic and therapeutic tools, have a major disadvantage due to their inherent cytotoxic nature. The cellular interaction, uptake and resultant toxic influence of CdTe QDs (gelatinised and non-gelatinised Thioglycolic acid (TGA) capped) have been investigated with pheochromocytoma 12 (PC12) cells. In conjunction to their analysis by confocal microscopy, the QD - cell interplay was explored as the QD concentrations were varied over extended (up to 72 hours) co-incubation times. Coupled to this investigation, cell viability, DNA quantification and cell proliferation assays were also performed to compare and contrast the various factors leading to cell stress and ultimately death. Results Thioglycolic acid (TGA) stabilised CdTe QDs (gel and non - gel) were co-incubated with PC12 cells and investigated as to how their presence influenced cell behaviour and function. Cell morphology was analysed as the QD concentrations were varied over co-incubations up to 72 hours. The QDs were found to be excellent fluorophores, illuminating the cytoplasm of the cells and no deleterious effects were witnessed at concentrations of ~10-9 M. Three assays were utilised to probe how individual cell functions (viability, DNA quantification and proliferation) were affected by the presence of the QDs at various concentrations and incubation times. Cell response was found to not only be concentration dependant but also influenced by the surface environment of the QDs. Gelatine capping on the surface acts as a barrier towards the leaking of toxic atoms, thus reducing the negative impact of the QDs. Conclusion This study has shown that under the correct conditions, QDs can be routinely used for the imaging of PC12 cells with minimal adverse effects. We have found that PC12 cells are highly susceptible to an increased concentration range of the QDs, while the gelatine coating acts as a barrier towards enhanced toxicity at higher QD concentrations.

Abstract Background Despite the implementation of prevention guidelines, early-onset group B streptococci (GBS) disease remains a cause of neonatal morbidity and mortality worldwide. Strategies to identify women who are at risk of transmitting GBS to their infant and the administration of intrapartum antibiotics have greatly reduced the incidence of neonatal GBS disease. However, there is a requirement for a rapid diagnostic test for GBS that can be carried out in a labour ward setting especially for women whose GBS colonisation status is unknown at the time of delivery. We report the design and evaluation of a real-time PCR test (RiboSEQ GBS test) for the identification of GBS in vaginal swabs from pregnant women. Methods The qualitative real-time PCR RiboSEQ GBS test was designed based on the bacterial ssrA gene and incorporates a competitive internal standard control. The analytical sensitivity of the test was established using crude lysate extracted from serial dilutions of overnight GBS culture using the IDI Lysis kit. Specificity studies were performed using DNA prepared from a panel of GBS strains, related streptococci and other species found in the genital tract environment. The RiboSEQ GBS test was evaluated on 159 vaginal swabs from pregnant women and compared with the GeneOhm™ StrepB Assay and culture for the identification of GBS. Results The RiboSEQ GBS test is specific and has an analytical sensitivity of 1-10 cell equivalents. The RiboSEQ GBS test was 96.4% sensitive and 95.8% specific compared to "gold standard" culture for the identification of GBS in vaginal swabs from pregnant women. In this study, the RiboSEQ GBS test performed slightly better than the commercial BD GeneOhm™ StrepB Assay which gave a sensitivity of 94.6% and a specificity of 89.6% compared to culture. Conclusion The RiboSEQ GBS test is a valuable method for the rapid, sensitive and specific detection of GBS in pregnant women. This study also validates the ssrA gene as a suitable and versatile target for nucleic acid-based diagnostic tests for bacterial pathogens.

Abstract Background Trypanosomes undergo extensive developmental changes during their complex life cycle. Crucial among these is the transition between slender and stumpy bloodstream forms and, thereafter, the differentiation from stumpy to tsetse-midgut procyclic forms. These developmental events are highly regulated, temporally reproducible and accompanied by expression changes mediated almost exclusively at the post-transcriptional level. Results In this study we have examined, by whole-genome microarray analysis, the mRNA abundance of genes in slender and stumpy forms of T.brucei AnTat1.1 cells, and also during their synchronous differentiation to procyclic forms. In total, five biological replicates representing the differentiation of matched parasite populations derived from five individual mouse infections were assayed, with RNAs being derived at key biological time points during the time course of their synchronous differentiation to procyclic forms. Importantly, the biological context of these mRNA profiles was established by assaying the coincident cellular events in each population (surface antigen exchange, morphological restructuring, cell cycle re-entry), thereby linking the observed gene expression changes to the well-established framework of trypanosome differentiation. Conclusion Using stringent statistical analysis and validation of the derived profiles against experimentally-predicted gene expression and phenotypic changes, we have established the profile of regulated gene expression during these important life-cycle transitions. The highly synchronous nature of differentiation between stumpy and procyclic forms also means that these studies of mRNA profiles are directly relevant to the changes in mRNA abundance within individual cells during this well-characterised developmental transition.

Abstract Background Preterm labour occurs in approximately 10% of pregnancies and is a major cause of infant morbidity and mortality. However, the pathways involved in regulating contractility in normal and preterm labour are not fully elucidated. Our aim was to utilise a human myometrial contractility model to investigate the effect of a number of uterine specific contractility agents in this system. Therefore, we investigated the contractile response of human primary uterine smooth muscle cells or immortalised myometrial smooth muscle cells cultured within collagen lattices, to known mediators of uterine contractility, which included thrombin, the ROCK-1 inhibitor Y-27632, tumour necrosis factor alpha (TNF alpha) and the non-steroidal anti-inflammatory indomethacin. Methods Cell contractility was calculated over time, with the collagen gel contraction assay, utilising human primary uterine smooth muscle cells (hUtSMCs) and immortalised myometrial smooth muscle cells (hTERT-HM): a decrease in collagen gel area equated to an increase in contractility. RNA was isolated from collagen embedded cells and gene expression changes were analysed by real time fluorescence reverse transcription polymerase chain reaction. Scanning electron and fluorescence microscopy were employed to observe cell morphology and cell collagen gel interactions. Statistical analysis was performed using ANOVA followed by Tukey's post hoc tests. Results TNF alpha increased collagen contractility in comparison to the un-stimulated collagen embedded hUtSMC cells, which was inhibited by indomethacin, while indomethacin alone significantly inhibited contraction. Thrombin augmented the contractility of uterine smooth muscle cell and hTERT-HM collagen gels, this effect was inhibited by the thrombin specific inhibitor, hirudin. Y-27632 decreased both basal and thrombin-induced collagen contractility in the hTERT-HM embedded gels. mRNA expression of the thrombin receptor, F2R was up-regulated in hUtSMCs isolated from collagen gel lattices, following thrombin-stimulated contractility. Conclusion TNF alpha and thrombin increased uterine smooth muscle cell collagen contractility while indomethacin had the opposite effect. Thrombin-induced collagen contractility resulted in F2R activation which may in part be mediated by the ROCK-1 pathway. This study established the in vitro human myometrial model as a viable method to assess the effects of a range of uterotonic or uterorelaxant agents on contractility, and also permits investigation of the complex regulatory pathways involved in mediating myometrial contractility at labour.

Abstract Background The origin and early evolution of the active site of the ribosome can be elucidated through an analysis of the ribosomal proteins' taxonomic block structures and their RNA interactions. Comparison between the two subunits, exploiting the detailed three-dimensional structures of the bacterial and archaeal ribosomes, is especially informative. Results The analysis of the differences between these two sites can be summarized as follows: 1) There is no self-folding RNA segment that defines the decoding site of the small subunit; 2) there is one self-folding RNA segment encompassing the entire peptidyl transfer center of the large subunit; 3) the protein contacts with the decoding site are made by a set of universal alignable sequence blocks of the ribosomal proteins; 4) the majority of those peptides contacting the peptidyl transfer center are made by bacterial or archaeal-specific sequence blocks. Conclusion These clear distinctions between the two subunit active sites support an earlier origin for the large subunit's peptidyl transferase center (PTC) with the decoding site of the small subunit being a later addition to the ribosome. The main implications are that a single self-folding RNA, in conjunction with a few short stabilizing peptides, formed the precursor of the modern ribosomal large subunit in association with a membrane. Reviewers This article was reviewed by Jerzy Jurka, W. Ford Doolittle, Eugene Shaknovich, and George E. Fox (nominated by Jerzy Jurka).

Abstract Background RHOGTPases play a significant role in modulating myometrial contractility in uterine smooth muscle. They are regulated by at least three families of proteins, RHO guanine nucleotide exchange factors (RHOGEFs), RHOGTPase-activating proteins (RHOGAPs) and RHO guanine nucleotide inhibitors (RHOGDIs). RHOGEFs activate RHOGTPases from the inactive GDP-bound to the active GTP-bound form. RHOGAPs deactivate RHOGTPases by accelerating the intrinsic GTPase activity of the RHOGTPases, converting them from the active to the inactive form. RHOGDIs bind to GDP-bound RHOGTPases and sequester them in the cytosol, thereby inhibiting their activity. Ezrin-Radixin-Moesin (ERM) proteins regulate the cortical actin cytoskeleton, and an ERM protein, moesin (MSN), is activated by and can also activate RHOGTPases. Methods We therefore investigated the expression of various RHOGEFs, RHOGAPs, a RHOGDI and MSN in human myometrium, by semi-quantitative reverse transcription PCR, real-time fluorescence RT-PCR, western blotting and immunofluorescence microscopy. Expression of these molecules was also examined in myometrial smooth muscle cells. Results ARHGEF1, ARHGEF11, ARHGEF12, ARHGAP5, ARHGAP24, ARHGDIA and MSN mRNA and protein expression was confirmed in human myometrium at term pregnancy, at labour and in the non-pregnant state. Furthermore, their expression was detected in myometrial smooth muscle cells. It was determined that ARHGAP24 mRNA expression significantly increased at labour in comparison to the non-labour state. Conclusion This study demonstrated for the first time the expression of the RHOGTPase regulators ARHGEF1, ARHGEF11, ARHGEF12, ARHGAP5, ARHGAP24, ARHGDIA and MSN in human myometrium, at term pregnancy, at labour, in the non-pregnant state and also in myometrial smooth muscle cells. ARHGAP24 mRNA expression significantly increased at labour in comparison to the non-labouring state. Further investigation of these molecules may enable us to further our knowledge of RHOGTPase regulation in human myometrium during pregnancy and labour.

No abstract available for this article. [ABSTRACT FROM PUBLISHER]

Abstract Background Large-conductance, calcium-activated potassium (Maxi-K) channels are implicated in the modulation of human uterine contractions and myometrial Ca2+ homeostasis. However, the regulatory mechanism(s) governing the expression of Maxi-K channels with decreased calcium sensitivity at parturition are unclear. The objectives of this study were to investigate mRNA expression of the Maxi-K alpha subunit, and that of its splice variants, in human non-pregnant and pregnant myometrium, prior to and after labour onset, to determine whether altered expression of these splice variants is associated with decreased calcium sensitivity observed at labour onset. Methods Myometrial biopsies were obtained at hysterectomy (non-pregnant, NP), and at Caesarean section, at elective (pregnant not-in-labour, PNL) and intrapartum (pregnant in-labour, PL) procedures. RNA was extracted from all biopsies and quantitative real-time RT-PCR was used to investigate for possible differential expression of the Maxi-K alpha subunit, and that of its splice variants, between these functionally-distinct myometrial tissue sets. Results RT-PCR analysis identified the presence of a 132 bp and an 87 bp spliced exon of the Maxi-K alpha subunit in all three myometrial tissue sets. Quantitative real-time PCR indicated a decrease in the expression of the Maxi-K alpha subunit with labour onset. While there was no change in the proportion of Maxi-K alpha subunits expressing the 87 bp spliced exon, the proportion of alpha subunits expressing the 132 bp spliced exon was significantly increased with labour onset, compared to both non-pregnant and pregnant not-in-labour tissues. An increased proportion of 132 bp exon-containing alpha subunit variants with labour onset is of interest, as channels expressing this spliced exon have decreased calcium and voltage sensitivities. Conclusions Our findings suggest that decreased Maxi-K alpha subunit mRNA expression in human myometrium at labour onset, coupled to an increased proportion of Maxi-K channels expressing the 132 bp spliced exon, may be linked to decreased Maxi-K channel calcium and voltage sensitivity, thereby promoting enhanced uterine activity at the time of labour.

Abstract Background Recent studies in children have demonstrated that frequent occurrence of parasomnias is related to increased sleep disruption, mental disorders, physical harm, sleep disordered breathing, and parental duress. Although there have been several cross-sectional and clinical studies of parasomnias in children, there have been no large, population-based studies using full polysomnography to examine the association between parasomnias and sleep disordered breathing. The Tucson Children's Assessment of Sleep Apnea study is a community-based cohort study designed to investigate the prevalence and correlates of objectively measured sleep disordered breathing (SDB) in pre-adolescent children six to 11 years of age. This paper characterizes the relationships between parasomnias and SDB with its associated symptoms in these children. Methods Parents completed questionnaires pertaining to their child's sleep habits. Children had various physiological measurements completed and then were connected to the Compumedics PS-2 sleep recording system for full, unattended polysomnography in the home. A total of 480 unattended home polysomnograms were completed on a sample that was 50% female, 42.3% Hispanic, and 52.9% between the ages of six and eight years. Results Children with a Respiratory Disturbance Index of one or greater were more likely to have sleep walking (7.0% versus 2.5%, p < 0.02), sleep talking (18.3% versus 9.0%, p < 0.006), and enuresis (11.3% versus 6.3%, p < 0.08) than children with an Respiratory Disturbance Index of less than one. A higher prevalence of other sleep disturbances as well as learning problems was observed in children with parasomnia. Those with parasomnias associated with arousal were observed to have increased number of stage shifts. Small alterations in sleep architecture were found in those with enuresis. Conclusions In this population-based cohort study, pre-adolescent school-aged children with SDB experienced more parasomnias than those without SDB. Parasomnias were associated with a higher prevalence of other sleep disturbances and learning problems. Clinical evaluation of children with parasomnias should include consideration of SDB.

Abstract Background Many current gene prediction methods use only one model to represent protein-coding regions in a genome, and so are less likely to predict the location of genes that have an atypical sequence composition. It is likely that future improvements in gene finding will involve the development of methods that can adequately deal with intra-genomic compositional variation. Results This work explores a new approach to gene-prediction, based on the Self-Organizing Map, which has the ability to automatically identify multiple gene models within a genome. The current implementation, named RescueNet, uses relative synonymous codon usage as the indicator of protein-coding potential. Conclusions While its raw accuracy rate can be less than other methods, RescueNet consistently identifies some genes that other methods do not, and should therefore be of interest to gene-prediction software developers and genome annotation teams alike. RescueNet is recommended for use in conjunction with, or as a complement to, other gene prediction methods.

Finding effective ways to prevent adolescent pregnancy is a concern of public health officials, educators, social workers, parents, and legislators. Numerous programs exist, but there is debate as to whether it is the specific program itself or other factors that are responsible for participants' successful outcomes. Using a quasi-experimental design, this study sought to determine which factors predicted changes in knowledge and beliefs among middle school students (N = 1,450) after exposure to Postponing Sexual Involvement (PSI), the curricular component of Education Now and Babies Later (ENABL), a pregnancy prevention program. It was found that the single most important predictor of improvement in knowledge and beliefs about pregnancy prevention was PSI itself, not background variables. The findings contradict some of the previous studies on factors impacting teenage pregnancy and lend support for the continued examination of ENABL as a promising component of pregnancy prevention efforts. [ABSTRACT FROM AUTHOR]

On the basis of past theory and research, it is hypothesized that adolescent females will spend more time in conversation and less time alone than their male counterparts. The hypotheses are tested in data from 2,004 seventh and ninth grade students in a southeastern metropolitan area. With a number of potentially relevant variables taken into account, self-reports of average number of hours per week spent alone and spent in conversation are both substantially higher among girls than among boys contradicting the time alone hypothesis but supporting the conversation time hypothesis and the generalizability of an earlier finding of an adolescent gender difference in time spent in conversation. The findings are tentatively interpreted in terms of males' orientation toward sports, encouraging nonconversation time with others, and females' orientation toward close interpersonal relationships, encouraging talk with intimates. In additional nonhypothesized findings, black students report significantly more conversation time and time alone than do white students. [ABSTRACT FROM AUTHOR]

The African claw-toed frog, Xenopus laevis, is a well-established laboratory model for the biology of vertebrate oogenesis, fertilisation, and development at embryonic, larval, and metamorphic stages. For ovulation, X. laevis females are usually injected with chorionic gonadotropin, whereupon they lay typically hundreds to thousands of eggs in a day. After being rested for a minimum of three months, animals are re-used. The literature suggests that adult females can lay much larger numbers of eggs in a short period. Here, we compared the standard "single ovulation" protocol with a "double ovulation" protocol, in which females were ovulated, then re-ovulated after seven days and then rested for three months before re-use. We quantified egg number, fertilisation rate (development to cleavage stage), and corticosterone secretion rate as a measure of stress response for the two protocol groups over seven 3-month cycles. We found no differences in egg number-per-ovulation or egg quality between the groups and no long-term changes in any measures over the 21-month trial period. Corticosterone secretion was elevated by ovulation, similarly for the single ovulation as for the first ovulation in the double-ovulation protocol, but more highly for the second ovulation (to a level comparable to that seen following shipment) in the latter. However, both groups exhibited the same baseline secretion rates by the time of the subsequent cycle. Double ovulation is thus transiently more stressful/demanding than single ovulation but within the levels routinely experienced by laboratory X. laevis. Noting that "stress hormone" corticosterone/cortisol secretion is linked to physiological processes, such as ovulation, that are not necessarily harmful to the individual, we suggest that the benefits of a doubling in egg yield-per-cycle per animal without loss of egg quality or signs of acute or long-term harm may outweigh the relatively modest and transient corticosterone elevation we observed. The double ovulation protocol therefore represents a potential new standard practice for promoting the "3Rs" (animal use reduction, refinement and replacement) mission for Xenopus research., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Moss et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Individuals with schizophrenia are at higher risk for severe COVID-19 illness and severe breakthrough infection following vaccination. It is unclear whether immune response to vaccination differs in this population., Objective: To assess whether anti-SARS-CoV-2 spike antibody titers after vaccination differ in people with a diagnosis of schizophrenia or schizoaffective disorder (SZ) compared to controls without a psychiatric disorder., Design: This cohort study assessed antibody response following the first and second dose of mRNA vaccines at longitudinal timepoints, up to 7 weeks following the first dose of vaccine., Setting: A multi-center study including psychiatric healthcare settings in the United States and Europe., Participants: 205 adults with no history of COVID-19 infection, including 106 individuals with SZ and 99 controls without a psychiatric disorder, who received their first dose of SARS-CoV-2 mRNA vaccine between December 20, 2020 and May 27, 2021., Main Outcomes and Measures: Mean SARS-CoV-2 anti-Spike IgG antibody levels within 7 weeks after the first dose of vaccination., Results: A total of 205 individuals (mean [SD] age, 44.7 [12.0] years; 90 [43.9%] male) were included, of which 106 (51.7%) were diagnosed with SZ. SZ was associated with lower mean log antibody levels (-0.15; 95% CI, -0.27 to -0.03, P  = 0.016) after adjusting for age, sex, body mass index, smoking, days since vaccination, and vaccine manufacturer. In secondary analyses of dose-specific responses, SZ was associated with a lower mean log antibody level after the second dose of vaccine (-0.23; 95% CI -0.39 to -0.06, P  = 0.006), but not the first dose of vaccine (0.00; 95% CI -0.18- 0.19, P  = 0.96)., Conclusions and Relevance: In this cohort study of individuals with SZ and a control group without psychiatric disorders, SZ was associated with lower SARS-CoV-2 anti-spike antibody levels following 2 doses of SARS-CoV-2 mRNA vaccination. This highlights the need for further studies assessing vaccine immunogenicity in individuals with schizophrenia., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)

Objective: Determine interactions between geospatial and socioeconomic factors influencing cleft lip and/or cleft palate (CL/P) management and outcomes., Design: Retrospective review and outcomes analysis (n = 740)., Setting: Urban academic tertiary care center., Patients: 740 patients undergoing primary (CL/P) surgery from 2009 to 2019., Main Outcomes Measures: Prenatal evaluation by plastic surgery, nasoalveolar molding, cleft lip adhesion, and age at CL/P surgery., Results: Prenatal evaluation by plastic surgery was predicted by the interaction between higher patient median block group income and shorter patient distance from the care center (OR = 1.07, p  = 0.022). Nasoalveolar molding was also predicted by the interaction between higher patient median block group income and shorter distance from the care center (OR = 1.28, p  = 0.016), whereas cleft lip adhesion was predicted by higher patient median block group income alone (OR = 0.41, p  < 0.001). Lower patient median block group income predicted later age at cleft lip (β = -67.25, p  = 0.011) and cleft palate (β = -46.35, p  = 0.050) repair surgery., Conclusions: Distance from the care center and lower median income by block group interacted to significantly predict prenatal evaluation by plastic surgery and nasoalveolar molding for patients with CL/P at a large, urban, tertiary care center. Patients living farthest from the care center who received prenatal evaluation by plastic surgery or who underwent nasoalveolar molding had higher median block group income. Future work will determine mechanisms perpetuating these barriers to care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The authors examined changes in perceived anxiety, stress, and mental health symptoms (i.e., psychological distress) reported by recipients of New York State public mental health services during the early months of the COVID-19 pandemic, as well as whether these changes varied by demographic characteristics or pandemic-related socioeconomic challenges., Methods: A statewide survey of service recipients (N=3,483) was conducted (May 8-June 22, 2020). Descriptive analyses were summarized, and logistic regression was used to evaluate associations between increases in reported psychological distress and age, gender, region of residence, race and ethnicity, socioeconomic challenges, and alcohol or drug use., Results: Fifty-five percent of respondents (N=1,933) reported a slight or moderate increase in COVID-19-related psychological distress, and 15% (N=520) reported a substantial increase. In adjusted models, substantial elevations in psychological distress were associated with identifying as female (AOR=1.83, 95% CI=1.50-2.25), experiencing three or more pandemic-related socioeconomic challenges (AOR=2.41, 95% CI=1.91-3.03), and reporting increased use of alcohol or drugs (AOR=1.81, 95% CI=1.34-2.44). Compared with non-Hispanic/Latinx White service recipients, non-Hispanic/Latinx Black individuals had lower odds of reporting substantially increased psychological distress (AOR=0.59, 95% CI=0.45-0.76), as did non-Hispanic/Latinx Asian-descent individuals (AOR=0.28, 95% CI=0.12-0.64)., Conclusions: In this large sample of recipients of New York State public mental health services, the COVID-19 pandemic's impact on psychological well-being was widespread and varied by gender, race and ethnicity, and socioeconomic vulnerability. These relationships must be considered in ongoing efforts to provide optimal care for this population., Competing Interests: The authors report no financial relationships with commercial interests.

Background: Recently we showed that a brief video-based intervention can improve openness to help-seeking and decrease treatment-related stigma among essential workers, particularly for female and Black individuals viewing demographically matched protagonists. The current randomized controlled trial explored two additional factors which may enhance the efficacy of this intervention: income level, known to be associated with help-seeking, and emotional engagement, which may enhance a person's ability to engage with the intervention. We hypothesized that income level and emotional engagement would correlate with changes in openness to help-seeking ("openness") and stigma., Methods: Essential workers (N = 1405) randomly viewed a control video or a brief video of an actor portraying an essential worker describing COVID-19-related anxiety and depression and treatment benefits. Openness and stigma were assessed at baseline, post-intervention, and 30-day follow-up, with emotional engagement assessed post-intervention., Results: The brief video intervention demonstrated immediate increases in openness (p < 0.001, Cohen's d = 0.39) and decreases in stigma (p < 0.001, d = 0.14) compared to the control. Reported income level affected neither dependent variable. Participants who scored higher on the emotional engagement scale reported greater change in openness and stigma., Limitations: Use of a crowdsourcing platform may limit generalizability., Conclusions: The 3-min video showed modest effect sizes for immediate increased openness and reduced stigma, with greater emotional engagement heightening the effect, suggesting a possible mediator to the intervention. Income level did not affect intervention outcomes. Research should explore the role of income by adding income-related content to the brief-video interventions and assessing whether links to referrals could foster immediate behavioral change., Trial Registration: NCT04964570., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest in relation to the subject of this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Individuals with mental illnesses experience disproportionately high rates of social adversities, chronic medical conditions, and early mortality. We analyzed a large, statewide dataset to explore associations between four social adversities and the presence of one or more, and then two or more, chronic medical conditions among individuals in treatment for mental illnesses in New York State. In Poisson regression models adjusting for multiple covariates (e.g., gender, age, smoking status, alcohol use), the presence of one or more adversities was associated with the presence of at least one medical condition (prevalence ratio (PR) = 1.21) or two or more medical conditions (PR = 1.46), and two or more adversities was associated with at least one medical condition (PR = 1.25) or two or more medical conditions (PR = 1.52) (all significant at p < .0001). Greater attention to primary, secondary, and tertiary prevention of chronic medical conditions is needed in mental health treatment settings, especially among those experiencing social adversities., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: The authors report no financial relationships with commercial interests.

Questions remain regarding whether the transition and continued use of telehealth was associated with changes in treatment engagement among patients with serious mental illness (SMI). Using NYS Medicaid claims, we identified 116,497 individuals with SMI receiving outpatient mental health services from September 1, 2019-February 28, 2021 and a comparison cohort of 101,995 from September 1, 2017-February 28, 2019 to account for unmeasured and seasonal variation. We characterized engagement in three 6-month increments (T 0 -T 1 -T 2 ) using clinically meaningful measures of high, partial, low, and none. Subgroup differences were compared, and telehealth users were compared to those with only in-person visits. Engagement, as characterized, was largely maintained during COVID. The 19.0 % with only in-person visits during COVID had different characteristics than telehealth users. Telehealth use was greater among younger people by T 2 (33.1 %), women (57.7 %), non-Hispanic White people (38.9 %), and those with MDD (18.0 %), but lower among non-Hispanic Black people, in NYC, and those with schizophrenia or SUD. Most telehealth users were highly engaged (77.1 %); most using only in-person services had low engagement (47.5 %). The shift to telehealth preserved access to many outpatient services for this SMI population. Exploring reasons for not using telehealth may identify opportunities to increase care access., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Abstract: We sought to investigate associations of cumulative social adversities in four areas (low education, unemployment, homelessness, and criminal/legal involvement) with presence of comorbid alcohol and drug use disorders among individuals in treatment for mental illnesses. Using data from 103,416 adults in mental health treatment, generalized estimating equation modified Poisson models were used to estimate increased risk of having comorbid substance use disorders based on individual and/or cumulative number of social adversities present. Controlling for effects of sex, race/ethnicity, and region (New York City vs . the rest of the State), as well as for the other social adversities, each of four social adversities was associated with presence of substance use comorbidity. Relative to having none of the social adversities, the presence of one, two, three, or four was associated with an increased prevalence ratio (PR) of having substance use comorbidity: 1.44, 2.10, 2.66, and 2.92; all p 's < 0.0001. PRs were greater among female patients, and among Hispanics and those classified as other or multiracial compared with non-Hispanic Whites or non-Hispanic Blacks. Findings indicate substantial associations between four social adversities and presence of substance use comorbidity; the strength of association with the four social adversities is cumulative., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Quantification of cortisol concentration in hair has become a promising conservation tool for non-invasive monitoring of "stress" in wild populations, yet this method needs to be carefully validated for each species. The goals of the study were:•Immunologically validate two methods (study 1 and 2 respectively) to extract and quantify cortisol in the hair of wild Alpine marmots.•Compare the amount of cortisol extracted from hair samples using two methods i.e. cut into fine pieces (study 1) and hair samples pulverized using a ball mill (study 2).•Determine the extent to which methods in study 2 could provide individual specific hair cortisol (HC) measures when samples were taken from the same body location. Within and between individual variations in HC levels were examined from multiple hair samples from 14 subjects in study 2. We evaluated if inter-individual variations in HC levels could be explained by sex and age.At least twice the amount of cortisol was obtained per g/hair when samples were pulverized in a ball mill prior to extraction compared to when cut into pieces. Our methods demonstrated intra-individual consistency in HC at a given time point: inter-individual variation in HC was three times larger than within individual variance. Sex and age did not impact HC levels., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier B.V.)

Objective: Emerging cross-sectional data indicate that essential workers in the COVID-19 era face increased mental health risks. This study longitudinally examined clinical symptoms of generalized anxiety disorder, depression, and posttraumatic stress disorder (PTSD) among U.S. essential workers, including health care workers and workers in indispensable occupations such as manufacturing, food industry, construction, transportation, hospitality, and emergency services, during the COVID-19 pandemic. The authors anticipated high symptom levels and greater symptom severity among women versus men and among younger adults compared with older adults. Analyses also explored the association between COVID-19 vaccination status and clinical symptoms., Methods: This four-wave online survey study assessed clinical symptoms in a convenience sample of 4,136 essential workers at baseline and 14, 30, and 90 days between August and December 2021. Symptoms of anxiety, depression, and PTSD were measured with the Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Primary Care PTSD Screen instruments, respectively., Results: At every time point, 74%-78% of respondents reported symptoms of anxiety and depression, which were highest among younger adults (ages 18-22 years), females, and transgender respondents. Vaccinated participants had slightly higher symptom levels than unvaccinated respondents. Rates of clinical symptoms did not change significantly over time., Conclusions: Essential workers consistently reported symptoms of generalized anxiety, depression, or PTSD, especially younger adult, female, and transgender participants. The overwhelming and unprecedented nature of the COVID-19 pandemic underscores the need to offer mental health care to essential workers, especially those in these subgroups. Employers and administrators should support and proactively encourage employees to access care when needed., Competing Interests: Dr. Fisher has received funding support from the NVLD Project and from TeleSage, Inc., has received donor support for the Man O’ War Project for equine-assisted psychotherapy projects (including the Earl I. Mack Foundation, the David and Julia Koch Foundation, the Jockey Club, the Mary and Daniel Loughran Foundation, the Gulfstream Park Racing Association, Meta Aerospace Capital, Ltd., and Tactical Air Support), and has received royalties from the Research Foundation for Mental Hygiene. Dr. Lewis-Fernández had common stock ownership in Vistagen Therapeutics, sold November 2021, and received an honorarium for a training presentation from AbbVie. The other authors report no financial relationships with commercial interests.

Introduction: COVID-19 was associated with increases in non-natural cause mortality in the U.S., including deaths due to drug overdose, homicide, and motor vehicle crashes. Initial reports indicated higher rates of non-natural mortality among ethnoracial minority groups. This report aims to clarify these disparities by documenting trends in non-natural mortality across ethnoracial groups during the 2020 COVID-19 surge in New York State., Methods: We report monthly trends in non-natural cause mortality (overall and stratified by ethnoracial status) in New York State from January 2019 through December 2020, which included the COVID-19 onset in March 2020., Results: Total mean monthly unintentional overdose rates per 100,000 increased from 17.45 (before surge: January 2019-February 2020) to 23.19 (after surge: March 2020-December 2020) (mean difference=5.73, 95% CI=3.82, 7.65; p <0.001). Mean monthly homicide death rates increased from 2.34 before surge to 3.55 after surge (mean difference=1.20, 95% CI=0.60, 1.81; p <0.001), with the increase seen primarily in the non-Latinx Black population. Although increasing unintentional overdose death rates before surge equally affected non-Latinx White, Latinx, and non-Latinx Black persons, they remained high for non-Latinx Black persons but dropped for the other 2 groups after the pandemic onset. None of the ethnoracial subgroups showed significant increases in suicide or motor vehicle crash death rates., Conclusions: Non-Latinx Black persons showed disproportionately high and sustained increased rates of unintentional overdose and homicide death rates after the 2020 COVID-19 surge in New York State. Fatality review and death scene investigation research is needed to better understand these disparities., (© 2023 The Authors.)