Fetal Thymus Size at 19-22 Weeks of Gestation: A Possible Marker for the Prediction of Low Birth Weight?

INTRODUCTION: The purpose was to compare thymus size measured during second trimester screening of fetuses who were subsequently small for gestational age at birth (weight below 10th percentile, SGA group) with fetuses with normal birth weight (control group). We hypothesized that measuring the fetal thymic-thoracic ratio (TT-ratio) might help predict low birth weight. METHODS: Using three-vessel view echocardiograms from our archives, we measured the anteroposterior thymus size and the intrathoracic mediastinal diameter to derive TT-ratios in the SGA (n = 105) and control groups (n = 533) between 19+0 and 21+6 weeks of gestation. We analyzed the association between TT-ratio and SGA adjusted to the week of gestation using logistic regression. Finally, we determined the possible TT-ratio cut-off point for discrimination between SGA and control groups by means of receiver operating characteristics (ROC) curve analysis. RESULTS: The TT-ratio was significantly higher in the SGA group than in the control group (p < 0.001). An increase of the TT-ratio by 0.1 was associated with a 3.1-fold increase in the odds of diagnosing SGA. We determined that a possible discrimination cut-off point between SGA and healthy controls was achieved using a TT-ratio of 0.390 (area under the ROC curve 0.695). CONCLUSION: An increased TT-ratio may represent an additional prenatal screening parameter that improves the prediction of birth weight below the 10th percentile. Prospective studies are now needed to evaluate the use of fetal thymus size as predictive parameter for adverse fetal outcome.

Beliefs, attitudes and experiences of virtual overdose monitoring services from the perspectives of people who use substances in Canada: a qualitative study.

BACKGROUND: Solitary use of substances is a risk factor for substance use-related mortality. Novel e-health harm reduction interventions such as virtual overdose monitoring services (VOMS) have emerged in North America to improve access to emergency overdose support for people who use substances (PWUS). To date, little research has been published, and the perspectives of PWUS are needed to inform evaluation and policy efforts. OBJECTIVE: To explore the beliefs, values and perceptions of PWUS around using and accessing VOMS in Canada. METHODS: A qualitative study following grounded theory methodology was conducted. Using existing peer networks, purposive and snowball sampling was conducted to recruit PWUS (≥ 18 years) with previous experience with VOMS. Thematic analysis was used to analyze twenty-three interviews. Several methods were employed to enhance rigor, such as independent data coding and triangulation. RESULTS: Twenty-three one-on-one telephone interviews of PWUS with previous experience with VOMS were completed and analyzed. The following themes emerged: (1) feelings of optimism around VOMS to save lives; (2) privacy/confidentiality was highly valued due to stigma and fear of arrest; (3) concerns with reliable cell phones negatively impacting VOMS uptake; (4) concerns around emergency response times, specifically in rural/remote communities; (5) desire for trusting relationships with VOMS operators; (6) importance of mental health supports and referrals to psychosocial services; and (7) possible limited uptake due to low public awareness of VOMS. CONCLUSION: This qualitative study provided novel insights about the VOMS from the perspectives of PWUS. PWUS generally felt optimistic about the potential of VOMS as a suitable harm reduction intervention, but several potential barriers around accessing VOMS were identified that may limit uptake. Future research is warranted.

Strengthening Research that Answers Nutrition Questions of Public Health Importance: Leveraging the Experience of the USDA Nutrition Evidence Systematic Review Team.

The Nutrition Evidence Systematic Review (NESR) team conducts nutrition- and public health-related systematic reviews and is within the USDA's Center for Nutrition Policy and Promotion. NESR has collaborated with scientific experts to conduct systematic reviews on nutrition and public health topics for more than a decade and is uniquely positioned to share recommendations with the research community to strengthen research quality and impact, especially the evidence base that supports public health nutrition guidance, including future editions of the Dietary Guidelines for Americans. Leveraging the expertise of NESR and its systematic review process resulted in the following recommendations for the research community: a) use the strongest study design feasible with sufficient sample size(s); b) enroll study participants who reflect the diversity of the population of interest and report participant characteristics; c) use valid and reliable dietary assessment methods; d) describe the interventions or exposures of interest and use standard definitions to promote consistency; e) use valid and reliable health outcome measures; f) account for variables that may impact the relationship between nutrition-related interventions or exposures and health outcomes; g) carry out studies for a sufficient duration and include repeated measures, as appropriate; and h) report all relevant information to inform accurate interpretation and evaluation of study results. Implementing these recommendations can strengthen nutrition and public health evidence and increase its utility in future public health nutrition systematic reviews. However, implementation will require additional support from the entire research community, including scientific journals and funding agencies.

Investigating structural subdivisions of the anterior cingulate cortex in schizophrenia, with implications for treatment resistance and glutamatergic levels.

BACKGROUND: Abnormalities in the anterior cingulate cortex (ACC) are thought to play an important role in the pathophysiology of schizophrenia. Given regional variations in ACC structure, the present study aimed to examine ACC structural subdivisions and their relationships to treatment resistance and glutamatergic levels in schizophrenia. METHODS: This study included 100 patients with schizophrenia and 52 healthy controls from 2 cohorts. We applied non-negative matrix factorization to identify accurate and stable spatial components of ACC structure. Between groups, we compared ACC structural indices in each spatial component based on treatment resistance or response and tested relationships with ACC glutamate + glutamine levels. RESULTS: We detected reductions in cortical thickness and increases in mean diffusivity in the spatial components on the surface of the cingulate sulcus, especially in patients with treatment-resistant and clozapine-resistant schizophrenia. Notably, mean diffusivity in these components was higher in patients who did not respond to clozapine compared to those who did. Furthermore, these ACC structural alterations were related to elevated ACC glutamate + glutamine levels but not related to symptomatology or antipsychotic dose. LIMITATIONS: Sample sizes, cross-sectional findings and mixed antipsychotic status were limitations of this study. CONCLUSION: This study identified reproducible abnormalities in ACC structures in patients with treatment-resistant and clozapine-resistant schizophrenia. Given that these spatial components play a role in inhibitory control, the present study strengthens the notion that glutamate-related disinhibition is a common biological feature of treatment resistance in schizophrenia.

A Measure of Illness Awareness in Individuals With Nicotine Dependence-Nicotine Use Awareness and Insight Scale.

INTRODUCTION: Impaired illness awareness or the inability to recognize that one has a dependence on nicotine may be a major barrier to seeking cessation treatment. To better understand the role of impaired illness awareness on treatment-seeking behavior and clinical outcomes, we developed and examined the psychometric properties of a novel scale measuring illness awareness in individuals with dependence on nicotine. AIMS AND METHODS: We developed the Nicotine Use Awareness and Insight Scale (NAS), a 7-item self-report measure to assess the theoretical construct of illness awareness in individuals with dependence on nicotine (www.illnessawarenessscales.com). Data from participants 18 years of age or older were collected via a web-based survey company, Dynata. Participants with moderate dependence on nicotine were included, defined by a score of four or more on the Fagerström Test for Cigarette Dependence (FTCD) or the FTCD adapted for electronic cigarettes (eFTCD). RESULTS: A total of 100 participants (mean [SD] age = 49.1 [16.1] years, 52% women) that met the inclusion criteria for either FTCD (n = 50) or eFTCD (n = 50) were included. The NAS demonstrated good convergent (r = .74, p < .001) and discriminant validity (r = .03, p = .786). It also demonstrated good internal consistency (Cronbach's alpha = 0.78) and one-month test-retest reliability (intra-class correlation = 0.86). An exploratory factor analysis yielded the retention of two components. CONCLUSIONS: The NAS is a novel scale to asses illness awareness in individuals with dependence on nicotine. This study provides initial support for the psychometric validity and reliability of NAS. IMPLICATIONS: The NAS may be used in research and clinical practice to evaluate the impact of impaired illness awareness on treatment-seeking behavior and clinical outcomes.

Impaired insight into illness is unrelated to subjective happiness, success, and life satisfaction in schizophrenia.

BACKGROUND: Impaired insight into illness is a common feature of schizophrenia. Improved insight is associated with better treatment adherence and clinical outcomes. At the same time, improving insight has been suggested to increase depressive symptoms and diminish quality of life. The aim of this study was to examine the associations between impaired insight and degree of subjective happiness, perceived level of success, and life satisfaction in patients with schizophrenia spectrum disorders. METHODS: A total of 108 participants with schizophrenia or schizoaffective disorder were included. Data for this study were obtained from our group's previous investigation that examined the relationship between impaired insight and visuospatial attention. Insight into illness was measured by the VAGUS scale, which assesses general illness awareness, accurate symptom attribution, awareness of the need for treatment, and awareness of the negative consequences attributable to the illness. RESULTS: Our results revealed no association among the VAGUS average and subscale scores and degree of subjective happiness, perceived level of success, and life satisfaction. CONCLUSIONS: Our study suggests that insight into illness is not related to subjective happiness, life satisfaction, or perceived level of success in patients with schizophrenia, which is in contrast to previous reports that demonstrate an association between insight into illness and depression.

Epigenetics for Drug Discovery: Dissecting the Effect of High Antipsychotic Dosage and D2 Blockage on Peripheral DNA Methylation.

INTRODUCTION: The relationship between genetic polymorphisms of antipsychotic drug-metabolizing agents and drug receptors has been often investigated. DNA methylation is a form of epigenetic modification that regulates gene expression. Few studies have analyzed the relationship between genome-wide methylation patterns and antipsychotic dosage. The primary aim of this pilot study was to investigate the association between antipsychotic dosage and genome-wide DNA methylation in patients with schizophrenia (SCZ). METHODS: Current dosage of antipsychotic medications was assessed in 136 patients with SCZ. Dosage was standardized using three different methods: chlorpromazine equivalent dose (CPZe), defined daily dose (DDD), and percentage of Lexicomp maximum dose (PM%). DNA methylation was measured in white blood cells. Antipsychotic dosage was the primary outcome variable in a model, including genome-wide methylation status as the main predictor. RESULTS: This study did not show any association between DNA methylation and dosage variation for CPZe, PM%, and DDD. However, the probe cg271403389 was consistently associated with antipsychotic dosage across the three standardization methods. When looking at the genomic location of the most significant probes, we found that 15% were intergenic, 23% were in the distal promoter, 9% in the 3'untranslated region, 32% in the gene body, 3% in the 5' untranslated region, 15% in the proximal promoter, and 3% in the first exon. DISCUSSION: This study shows the importance of investigating the relationship between DNA methylation and optimal antipsychotic dosage to personalize treatment in SCZ. Future studies require larger prescription databases to build on the results of this analysis.

Integrated Plastic Surgery Residency Applicant Perceptions of Virtual Interviews.

PURPOSE: The 2020-2021 interview cycle for integrated plastic surgery applicants was the first to be held virtually because of the COVID-19 pandemic. Here, we detail the largest study on integrated plastic surgery applicant perceptions after the virtual interview cycle. METHODS: A 35-question institutional review board-approved survey was distributed to medical students who had applied to the Johns Hopkins/University of Maryland or University of California San Diego integrated residency programs during the 2020-2021 interview cycle. Survey questions assessed the structure, strengths, and weaknesses of the exclusively virtual interview process. Survey administration and data collection were performed using the Qualtrics platform. RESULTS: Of 318 distributed surveys, 94 were completed. In addition, 91.5% of respondents preferred in-person interviews before the interview season, whereas 54.3% preferred in-person interviews afterward. Applicants who favored virtual interviews did not view being unable to physically meet with program staff as a detriment (P = .001) and felt they could effectively advocate for themselves (P = .002). Overall, the most cited strengths were the ability to complete more interviews (P = .01) and cost benefits (P = .02). Criticisms were directed at the impersonal nature of the exchange (86.2%), lack of physical tour (56.4%), and difficulties at self-advocacy (52.1%). CONCLUSION: Preference for virtual interviews increased from 7.5% to 34.0% after the virtual interview cycle. For several students, the ideal interview structure permits both in-person and virtual interviews to maximize flexibility. Augmenting with virtual city tours and one-on-one interviews may mitigate the impersonal nature of virtual interviews as perceived by some applicants.

A Measure to Assess Illness Awareness in Problem Gambling: Gambling Awareness and Insight Scale (GAS).

Impaired subjective awareness of problem gambling may act as a barrier to help-seeking and treatment adherence. However, the impact of impaired problem gambling awareness on clinical and social outcomes has received little empirical study. The aim of this study was to develop and investigate the psychometric properties of a novel scale that measures impaired illness awareness in individuals with problem gambling. We developed the Gambling Awareness and Insight Scale (GAS), a self-report measure that assesses the core theoretical constructs of illness awareness in problem gambling, namely General Disorder or Problem Awareness, Accurate Symptom Attribution, Awareness of Need for Treatment and the Negative Consequences attributable to problem gambling ( www.illnessawarenessscales.com ). Data were acquired from an online survey platform, Dynata, to evaluate the psychometric properties of the GAS. A total of 100 participants aged 18 years or older with problem gambling defined by a score of 4 or more on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Pathological Gambling Diagnostic Form were included. The GAS demonstrated good convergent (r = 0.57, p < 0.001) and discriminant validity (r = - 0.18, p = 0.080). It also demonstrated good internal consistency (Cronbach's α = 0.80) and one-month test-retest reliability (intra-class correlation = 0.86). An exploratory factor analysis suggested retention of two components. The GAS is a novel psychometric tool designed to evaluate impaired subjective illness awareness in problem gambling. Initial evidence suggests that the GAS can be used in research and clinical settings to evaluate the impact of impaired problem gambling awareness on adherence to treatment programs, clinical and psychosocial outcomes. Replication in applied settings is needed.

Anti-vaccination attitudes are associated with less analytical and more intuitive reasoning.

Online anti-vaccination rhetoric has produced far reaching negative health consequences. Persons who endorse anti-vaccination attitudes may employ less analytical reasoning when problem solving. Considering limitations in previous research, we used an online web-based survey (n = 760; mean age = 47.69; 388 males, 372 females) to address this question. Analytical reasoning was negatively correlated with anti-vaccination attitudes (r = -.18, p < .0001). This relationship remained significant after statistically controlling for potential confounders, including age, sex, education, and religiosity (r = -.16, p < .0001). We hope that elucidating the cognitive, non-information-based aspects of anti-vaccination attitudes will help to guide effective educational interventions aimed at improving public health in the future.

Measuring amphetamine-induced dopamine release in humans: A comparative meta-analysis of [11 C]-raclopride and [11 C]-(+)-PHNO studies.

The radiotracers [11 C]-raclopride and [11 C]-(+)-PHNO are commonly used to measure differences in amphetamine-induced dopamine release between healthy persons and persons with neuropsychiatric diseases. As an agonist radiotracer, [11 C]-(+)-PHNO should theoretically be roughly 2.7 times more sensitive to displacement by endogenous dopamine than [11 C]raclopride. To date, only one study has been published comparing the sensitivity of these two radiotracers to amphetamine-induced dopamine release in healthy persons. Unfortunately, conflicting findings in the literature suggests that the dose of amphetamine they employed (0.3 mg/kg, p.o.) may not reliably reduce [11 C]-raclopride binding in the caudate. Thus, it is unclear whether the preponderance of evidence supports the theory that [11 C]-(+)-PHNO is more sensitive to displacement by amphetamine in humans than [11 C]-raclopride. In order to clarify these issues, we conducted a comparative meta-analysis summarizing the effects of amphetamine on [11 C]-raclopride and [11 C]-(+)-PHNO binding in healthy humans. Our analysis indicates that amphetamine given at 0.3 mg/kg, p.o. does not reliably reduce [11 C]-raclopride binding in the caudate. Second, the greater sensitivity of [11 C]-(+)-PHNO is evidenced at 0.5 mg/kg, p.o., but not at lower doses of amphetamine. Third, our analysis suggests that [11 C]-(+)-PHNO may be roughly 1.5 to 2.5 times more sensitive to displacement by amphetamine than [11 C]-raclopride in healthy persons. We recommend that future displacement studies with these radiotracers employ 0.5 mg/kg, p.o. of amphetamine with a dose, post-scan interval of at least 3 hr. Using this dose of amphetamine, [11 C]-raclopride studies should employ at least n = 34 participants per group, while [11 C]-(+)-PHNO studies should employ at least n = 6 participants per group, in order to be sufficiently powered (80%) to detect changes in radiotracer binding within the caudate.

Evaluation of digital otoscopy in pediatric patients: A prospective randomized controlled clinical trial.

BACKGROUND: Acute otitis media is often misdiagnosed. Pediatric trainees learn otoscopy from supervisors who cannot concurrently view the eardrum. Digital, smartphone otoscopes show promise to improve the visibility and learning due to a concurrent view by trainees and supervisors. We aimed to determine whether use of digital otoscopes improved accuracy of the ear exams between medical trainees and their supervisors, compared to using traditional otoscopes. Secondarily, we evaluated whether the use of digital otoscopes reduced the number of repeat ear examinations by supervisors, changed the trainee's confidence in their exam findings, and led to differences in the rate of antibiotics prescribed. METHODS: This study was a randomized controlled trial comparing use of a digital otoscope to a traditional otoscope, in a pediatric emergency department and primary care clinic in an academic tertiary care children's center. We used a modified validated image-based grading scale to compare accuracy of the ear exam between trainees and supervisors. Surveys documented modified OMgrade scores, frequency of supervisor exams, trainee confidence on a 5-point Likert scale, and antibiotic prescriptions. Inter-rater agreement of trainees and supervisors, the number of supervisor confirmatory examinations performed, trainee confidence, and antibiotic prescription rates were evaluated. RESULTS: Amongst 188 children, 375 ears were examined by 85 trainees and 22 supervisors. The digital otoscope was utilized in 92 (48.9%) exams and 96 (51.1%) used the traditional otoscope. Accuracy of ear exam findings between trainees and supervisors improved by 11.2% (95% CI: 1.5, 21.8%, p = 0.033) using the Cellscope Oto (74.8%, 95% CI: 67.3, 82.1%) compared to the traditional otoscope (63.5%, 95% CI: 56.7, 70.4%). Fewer repeat supervisor exams were performed in the digital otoscope group (27.2%) vs. the traditional otoscope group (97.9%) (p < 0.001). There was no difference in mean trainee confidence in their examination (p = 0.955) or antibiotic prescription rates when using digital versus traditional otoscopes (p = 0.071). CONCLUSIONS: Utilization of a digital otoscope resulted in increased accuracy of the ear exam between trainees and supervisors, and fewer total number of examinations performed on a given child. Compared to a traditional otoscope, a digital otoscope may be a more efficient and effective diagnostic tool.

Individual culture leads to decreased blastocyst formation but does not affect pregnancy outcomes in the setting of a single, vitrified-warmed euploid blastocyst transfer.

PURPOSE: To evaluate embryology and pregnancy outcomes following individual and group embryo culture in the setting of contemporary laboratory practices and freeze-all cycles. METHODS: Patients underwent ovarian stimulation followed by intracytoplasmic sperm injection (ICSI). Embryos proceeded through individual culture and then underwent preimplantation genetic testing for aneuploidy (PGT-A) via trophectoderm biopsy. In a subsequent cycle, participants underwent single embryo transfer of a vitrified-warmed, euploid embryo. Outcomes were compared to controls undergoing group culture during the same time frame. The Mann-Whitney U test and logistic regression models were utilized. RESULTS: Outcomes were assessed for 144 patients whose embryos underwent individual culture and 449 controls whose embryos underwent group culture. There were no significant differences in fertilization rates between groups (81.7% for individual culture vs. 84.1% for group culture, p = 0.22). However, individual culture was associated with a decreased rate of blastocyst formation compared to group culture (43.5% vs. 48.5%, p < 0.01). Following single, vitrified-warmed euploid blastocyst transfer, there were no significant differences between individual culture and group culture, respectively, in rates of positive ßhCG (81.9% vs. 81.5%, p = 0.91), sustained implantation (63.9% vs. 65.0%, p = 0.80), biochemical miscarriage (16.7% vs. 12.3%, p = 0.18), or clinical miscarriage (1.4% vs. 4.2%, p = 0.13). CONCLUSION: While individual culture appears to negatively impact the rate of usable blastocyst formation compared to group culture, there were no significant differences in pregnancy outcomes following transfer of a single, vitrified-warmed euploid blastocyst.

A method for measuring the effect of certified electronic health record technology on childhood immunization status scores among Medicaid managed care network providers.

OBJECTIVE: To provide a methodology for estimating the effect of U.S.-based Certified Electronic Health Records Technology (CEHRT) implemented by primary care physicians (PCPs) on a Healthcare Effectiveness Data and Information Set (HEDIS) measure for childhood immunization delivery. MATERIALS AND METHODS: This study integrates multiple health care administrative data sources from 2010 through 2014, analyzed through an interrupted time series design and a hierarchical Bayesian model. We compared managed care physicians using CEHRT to propensity-score matched comparisons from network physicians who did not adopt CEHRT. Inclusion criteria for physicians using CEHRT included attesting to the Childhood Immunization Status clinical quality measure in addition to meeting "Meaningful Use" (MU) during calendar year 2013. We used a first-presence patient attribution approach to develop provider-specific immunization scores. RESULTS: We evaluated 147 providers using CEHRT, with 147 propensity-score matched providers selected from a pool of 1253 PCPs practicing in Maryland. The estimate for change in odds of increasing immunization rates due to CEHRT was 1.2 (95% credible set, 0.88-1.73). DISCUSSION: We created a method for estimating immunization quality scores using Bayesian modeling. Our approach required linking separate administrative data sets, constructing a propensity-score matched cohort, and using first-presence, claims-based childhood visit information for patient attribution. In the absence of integrated data sets and precise and accurate patient attribution, this is a reusable method for researchers and health system administrators to estimate the impact of health information technology on individual, provider-level, process-based, though outcomes-focused, quality measures. CONCLUSION: This research has provided evidence for using Bayesian analysis of propensity-score matched provider populations to estimate the impact of CEHRT on outcomes-based quality measures such as childhood immunization delivery.

Clozapine response trajectories and predictors of non-response in treatment-resistant schizophrenia: a chart review study.

Although clozapine is the main antipsychotic medication for treatment-resistant schizophrenia, 40-70% of patients on clozapine have persistent psychotic symptoms (i.e. ultra-treatment-resistant schizophrenia, UTRS). We aimed to examine clozapine response/non-response patterns in patients with treatment-resistant schizophrenia, as well as determine patient clinico-demographic factors associated with long-term clozapine non-response. Clinico-demographic characteristics of 241 patients on clozapine were collected through a retrospective chart review. The median (interquartile range, IQR) follow-up from illness onset was 25.0 (IQR = 24.0) years. Clozapine response was assessed at median 10.8 (IQR = 14.0) months (Time 1, T1) and 7.2 (IQR = 13.5) years (Time 2, T2) after its initiation. It was evaluated by chart reviewers based on the information provided in clinical notes. Binomial logistic regression was used to determine clinico-demographic factors associated with clozapine non-response at both T1 and T2 (i.e. stable UTRS, S-UTRS) compared to clozapine response at both times (i.e. stable clozapine responders, S-ClozResp). Among clozapine responders (n = 122) at T1, 83.6% remained clozapine responsive and 16.4% became non-responsive at T2. In the UTRS group (n = 119) at T1, 87.4% remained clozapine non-responsive and 12.6% became responsive at T2. Duration of delay in clozapine initiation (OR = 0.94, Wald χ2 = 5.33, p = 0.021) and number of pre-clozapine hospitalizations (OR = 0.95, Wald χ2 = 5.20, p = 0.023) were associated with S-UTRS. Most UTRS patients were non-responsive to clozapine from the start of treatment. Preventing delay in initiating clozapine and relapses could help promote long-term clozapine response in patients with treatment-resistant schizophrenia. Future longitudinal studies are required to explore the neuropathological correlates of relapses and delay in clozapine initiation.

The appraisal of body content (ABC) trial: obesity does not significantly impact gamete production in infertile men and women.

PURPOSE: As obesity becomes increasingly prevalent, its impact on fertility has been a subject of great debate. Nearly all prior research is retrospective and evaluates obesity utilizing body mass index (BMI), which may overestimate adiposity in individuals with a greater amount of lean muscle and underestimate adiposity in those with less muscle mass. METHODS: We prospectively evaluated 2013 couples undergoing infertility treatment with in vitro fertilization (IVF). Percent body fat (%BF) was measured by use of a bioelectric impedance analysis (BIA) scale at baseline. BMI was also determined. Ovarian reserve parameters, ovarian response to controlled ovarian hyperstimulation, and semen analyses were measured in correlation with their %BF and BMI. RESULTS: Females classified as obese based on %BF or BMI had lower serum FSH. However, when the analysis was limited to women without PCOS (n = 1706), obesity based on %BF or BMI was associated with lower serum AMH. Female obesity-regardless of a PCOS diagnosis-did not affect number of mature oocytes retrieved. Males who were in obese %BF category were found to have lower TMSC compared with normal weight counterparts (p < 0.05); however, the observed decrease was not significant enough to limit the success of assisted reproductive technologies. CONCLUSIONS: These findings suggest that while obesity may affect ovarian reserve in women variably depending on presence of PCOS, it does not affect number of mature oocytes available after COH. Similarly, while a high %BF in males is associated with lower TMSC, the observed difference is unlikely to affect IVF outcomes.

Impaired Awareness of Problem and Pathological Gambling: A Review.

Although well-recognized and clinically relevant, impaired awareness of problem and pathological gambling (IAPPG) is a poorly understood phenomenon that contributes to treatment denial and negative clinical and social outcomes. In this study, we aimed to conduct a systematic review of the measures available to assess problem gambling awareness, evaluate their psychometric properties, and determine the extent to which they cover the core domains of illness awareness: General Disorder Awareness, Symptom Attribution, Awareness of Need for Treatment, and Awareness of Negative Consequences. A systematic search using OVID database (Medline®, PsycINFO, and Embase) was performed to identify English language papers describing gambling awareness measures. We identified only 8 measures partially assessing IAPPG. Measures differed in their effectiveness and comprehensiveness in evaluating IAPPG. Most measures were principally developed to evaluate barriers or motivators to treatment-seeking among gamblers and were not specific to IAPPG. Two were psychometrically validated, but the items were not specific to the evaluation of subjective awareness of the disorder and they only covered up to two domains of IAPPG. With the development and psychometric validation of an easy-to-use, comprehensive measure of subjective IAPPG, future studies will be able to investigate the role of IAPPG in help-seeking behavior, treatment adherence, and clinical and social outcomes.

The conserved actinobacterial transcriptional regulator FtsR controls expression of ftsZ and further target genes and influences growth and cell division in Corynebacterium glutamicum.

BACKGROUND: Key mechanisms of cell division and its regulation are well understood in model bacteria such as Escherichia coli and Bacillus subtilis. In contrast, current knowledge on the regulation of cell division in Actinobacteria is rather limited. FtsZ is one of the key players in this process, but nothing is known about its transcriptional regulation in Corynebacterium glutamicum, a model organism of the Corynebacteriales. RESULTS: In this study, we used DNA affinity chromatography to search for transcriptional regulators of ftsZ in C. glutamicum and identified the Cg1631 protein as candidate, which was named FtsR. Both deletion and overexpression of ftsR caused growth defects and an altered cell morphology. Plasmid-based expression of native ftsR or of homologs of the pathogenic relatives Corynebacterium diphtheriae and Mycobacterium tuberculosis in the ΔftsR mutant could at least partially reverse the mutant phenotype. Absence of ftsR caused decreased expression of ftsZ, in line with an activator function of FtsR. In vivo crosslinking followed by affinity purification of FtsR and next generation sequencing of the enriched DNA fragments confirmed the ftsZ promoter as in vivo binding site of FtsR and revealed additional potential target genes and a DNA-binding motif. Analysis of strains expressing ftsZ under control of the gluconate-inducible gntK promoter revealed that the phenotype of the ΔftsR mutant is not solely caused by reduced ftsZ expression, but involves further targets. CONCLUSIONS: In this study, we identified and characterized FtsR as the first transcriptional regulator of FtsZ described for C. glutamicum. Both the absence and the overproduction of FtsR had severe effects on growth and cell morphology, underlining the importance of this regulatory protein. FtsR and its DNA-binding site in the promoter region of ftsZ are highly conserved in Actinobacteria, which suggests that this regulatory mechanism is also relevant for the control of cell division in related Actinobacteria.

Protein-Polymer Conjugates Synthesized Using Water-Soluble Azlactone-Functionalized Polymers Enable Receptor-Specific Cellular Uptake toward Targeted Drug Delivery.

Conjugation of proteins to drug-loaded polymeric structures is an attractive strategy for facilitating target-specific drug delivery for a variety of clinical needs. Polymers currently available for conjugation to proteins generally have limited chemical versatility for subsequent drug loading. Many polymers that do have chemical functionality useful for drug loading are often insoluble in water, making it difficult to synthesize functional protein-polymer conjugates for targeted drug delivery. In this work, we demonstrate that reactive, azlactone-functionalized polymers can be grafted to proteins, conjugated to a small-molecule fluorophore, and subsequently internalized into cells in a receptor-specific manner. Poly(2-vinyl-4,4-dimethylazlactone), synthesized using reversible addition-fragmentation chain transfer polymerization, was modified post-polymerization with substoichiometric equivalents of triethylene glycol monomethyl ether to yield reactive water-soluble, azlactone-functionalized copolymers. These reactive polymers were then conjugated to proteins holo-transferrin and ovotransferrin. Protein gel analysis verified successful conjugation of proteins to polymer, and protein-polymer conjugates were subsequently purified from unreacted proteins and polymers using size exclusion chromatography. Internalization experiments using a breast cancer cell line that overexpresses the transferrin receptor on its surface showed that the holo-transferrin-polymer conjugate was successfully internalized by cells in a mechanism consistent with receptor-mediated endocytosis. Internalization of protein-polymer conjugate demonstrated that the protein ligand maintained its overall structure and function following conjugation to polymer. Our approach to protein-polymer conjugate synthesis offers a simple, tailorable strategy for preparing bioconjugates of interest for a broad range of biomedical applications.

Mitochondria as a biomarker for IVF outcome.

Mitochondria play an essential role in generating energy for embryo development and maintaining embryo metabolism through key cellular functions including ion homeostasis, amino acid metabolism, glycolysis, fatty acid metabolism, signal transduction and apoptotic regulation. Recent literature suggests that mitochondrial content and function may be related to implantation success and embryo viability. Some studies have linked increased levels of mitochondrial DNA to aneuploidy, advanced maternal age and euploid blastocyst with implantation failure, while others have failed to demonstrate similar findings. This review aims to provide an overview of the current literature surrounding the possibilities of using mitochondria as an additional biomarker for infertility treatment outcome and summarize the reasons as to why there are inconsistencies in these studies.