Improved Mental Health, Social Connections and Sense of Self: A Mixed Methods Systematic Review Exploring the Impact and Experience of Community Reminiscence Programs.

Older people can experience health and social challenges such as loneliness, depression, and lack of social connectedness. One initiative that has been trialed to address these challenges is reminiscence programs. These programs can include music, art, photographs, sports, and general discussion to stimulate memories. This review aimed to systematically search for literature that explored the impact and experience of reminiscence programs for older people living in the community for the purposes of informing community programming. The PICOS framework was used to develop the review parameters and search strategy. Qualitative and quantitative research focused on community-based reminiscence programs were included. Commercially produced databases and grey literature were searched. The Critical Appraisal Skills Program qualitative critical appraisal tool and McMaster quantitative critical appraisal tool were used to assess the methodological quality of the included studies. Quantitative data were descriptively synthesized, and qualitative data were thematically analyzed, with each reported separately. Twenty-seven studies were included in the review. All quantitative studies (n = 17) provided clear information regarding the purpose, sample size, and justification. The measures adopted were reliable and valid. All studies reported clear data collection/analysis information and statistically significant findings. All qualitative studies (n = 10) clearly articulated a purpose with nine clearly describing recruitment, data collection, and researcher relationship. Synthesis of quantitative data demonstrated positive findings through a reduction in depression, anxiety, and loneliness and improvements in quality of life and mastery. These findings were supported and broadened by qualitative findings with three key themes identified: program processes, program ingredients, and program benefits. Providing opportunities for older adults to come together to tell stories about their past experiences may positively contribute to social outcomes. As reminiscence programs gain popularity, their implementation in practice should be underpinned by clear and reproducible practices.

Mental Health Conditions Increase Severe Maternal Morbidity By 50 Percent And Cost $102 Million Yearly In The United States.

Perinatal mental health disorders are increasingly acknowledged as contributors to adverse maternal outcomes. We analyzed data from the Healthcare Cost and Utilization Project National Inpatient Sample (2016 and 2017) to estimate hospitalization cost, length-of-stay, and severe maternal morbidity associated with perinatal mental health disorders overall, as well as stratified by payer and by specific mental health category. We found that people with mental health disorders had $458 higher costs per delivery hospitalization and 50 percent higher rates of severe maternal morbidity compared with people without mental health disorders. We estimated increased annual delivery hospitalization costs of $102 million in the US among people with perinatal mental health conditions compared with those without. Furthermore, people diagnosed with trauma- or stress-related mental health disorders had even higher rates of hospitalization costs-$825 higher per delivery-and 87 percent higher rates of severe maternal morbidity compared with people without those diagnoses. These findings provide important information for perinatal mental health program feasibility and cost-effectiveness analyses and suggest the need for increased focus on trauma- and stress-related disorders.

Race, Medicaid Coverage, and Equity in Maternal Morbidity.

BACKGROUND: Severe maternal morbidity (SMM) affects 50,000 deliveries in the United States annually, with around 1.5 times the rates among Medicaid-covered relative to privately covered deliveries. Furthermore, large racial inequities exist in SMM for non-Hispanic Black women and Hispanic women with rates being 2.1 and 1.4 times higher than White women, respectively. This study aimed to compare the differences in SMM among women of different races/ethnicities and delivery insurance types. Quantifying the rates of SMM based on the intersection of race/ethnicity and insurance status can help to elucidate how multiple forms of oppression and racism may contribute to the substantial inequities in SMM among Black women. METHODS: Using hospital discharge data from the Healthcare Cost and Utilization Project National Inpatient Sample (years 2016 and 2017), we conducted multivariate logistic models to evaluate equity in maternal outcomes among women with different primary payers, overall and stratified by race/ethnicity. RESULTS: We found a rate of SMM equal to 138.3 per 10,000 deliveries. Differences in the rate of SMM among non-Hispanic Black, non-Hispanic Asian, and Hispanic women relative to White women were lower among Medicaid-covered deliveries relative to deliveries of all payer types. For example, among all payers, Black women had 2.17 (221.3 vs. 102.1 per 10,000) times the rate of SMM compared with White women; however, among Medicaid-covered deliveries, Black women had 1.84 (227.3 vs. 123.2) times the rate. Despite increased risk associated with Medicaid coverage (adjusted odds ratio, 1.12; 95% confidence interval, 1.07-1.16), the risk was no longer significant in the stratified regression including Black women (adjusted odds ratio, 1.06; 95% confidence interval, 0.98-1.15). CONCLUSIONS: Our findings suggest that Black women with Medicaid do not have higher rates of SMM relative to Black women with private insurance. National and state policy efforts should continue to focus on addressing structural racism and other socioeconomic drivers of adverse maternal outcomes, including barriers to high-quality care among women with Medicaid coverage.

A Retrospective Descriptive Analysis of Sexual Assault Nurse Examiner Records From Sexual Assault Survivors at a Large University Emergency Department From 2003 to 2017.

This retrospective descriptive analysis of 837 patients seeking postassault care at an academic hospital in the United States describes characteristics of sexual assault survivors from a sociocultural context, with a specific focus on describing survivors presenting for sexual assault nurse examiner (SANE) exams and confirming existing literature on assault characteristics, such as disabilities and alcohol and/or drug use. Assaults resulting in SANE exams increased over time. Drug and/or alcohol use at the time of the assault was reported in 44.8% of cases and 20.8% of survivors reported having a disability. Understanding the demographic and sexual assault characteristics of survivors is fundamental to providing sensitive and responsive care.

Associations Between Comorbidities and Severe Maternal Morbidity.

OBJECTIVE: To evaluate the associations between the number of chronic conditions and maternal race and ethnicity (race) with the risk of severe maternal morbidity. METHODS: Using the National Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality, years 2016-2017, we examined risk of severe maternal morbidity among 1,480,925 delivery hospitalizations among women of different races and with different numbers of comorbid conditions using multivariable logistic regression. RESULTS: The rate of severe maternal morbidity was 139.7 per 10,000 deliveries. Compared with women with no comorbidities (rate 48.5/10,000), there was increased risk of severe maternal morbidity among women with one comorbidity (rate 238.6; odds ratio [OR] 5.0, 95% CI 4.8-5.2), two comorbidities (rate 379.9; OR 8.1, 95% CI 7.8-8.5), or three or more comorbidities (rate 560; OR 12.1, 95% CI 11.5-12.7). In multivariable regressions, similar associations were noted for women with one (adjusted odds ratio [aOR] 4.4, 95% CI 4.2-4.6), two (aOR 6.6, 95% CI 6.3-6.9), or three or more comorbidities (aOR 9.1, 95% CI 8.7-9.6). Black women had higher rates of comorbid conditions than all other racial and ethnic groups, with 55% (95% CI 54-56%) of Black women having no comorbidities, compared with 67% (95% CI 67-68%) of White women, 68% (95% CI 67-69%) of Hispanic women, and 72% (95% CI 71-73%) of Asian women. CONCLUSION: We found a dose-response relationship between number of comorbidities and risk of severe maternal morbidity, with the highest rates of severe maternal morbidity among women with three or more comorbidities. Focusing on the prevention and treatment of chronic conditions among women of childbearing age may have the potential to improve maternal outcomes across races and ethnicities.

The Effects of Different Sources of Stuttering Disclosure on the Perceptions of a Child Who Stutters.

Purpose This study measured between-group differences in perceived speech skills and personality characteristics of a 12-year-old boy who stutters as a function of a factual stuttering disclosure statement, delivered by the boy who stutters, his "mother," or his "teacher." Method Two hundred seventeen college-aged adults were randomly assigned to one of four groups, including a control group (no stuttering disclosure) and three experimental groups (child disclosure, mother disclosure, and teacher disclosure). Participants in the control condition viewed a brief video of a 12-year-old boy who stutters. For the experimental conditions, participants viewed a brief factual stuttering disclosure video (delivered by the child, mother, or teacher), followed by the same minute-long video of a boy who stutters used in the control condition. Following the videos, participants completed surveys relative to their perception of the boy's speech skills and personality characteristics. Results Results support previous research citing benefits of stuttering disclosure. Significant between-group differences in both perceived speech skills and personality characteristics were observed when stuttering was disclosed by not only the child who stutters but also his teacher. When stuttering was disclosed by the mother, limited positive attitudinal differences were observed in speech skills; as a matter of fact, a number of personality characteristics were perceived more negatively as a function of stuttering disclosure by the mother. Conclusions While results were generally most positive when the boy disclosed his own stuttering, data from this study support the efficacy of verbal stuttering disclosure provided by a teacher as a means of improving perceptions associated with stuttering. Accordingly, data support the notion that children who stutter will experience an improved quality of life when taught effective self-disclosure strategies by both parents and professionals, and that professionals (but not necessarily parents) can effectively disclose their clients' stuttering during this mentorship and self-advocacy process.

Identification of tRNA-derived small RNA (tsRNA) responsive to the tumor suppressor, RUNX1, in breast cancer.

Despite recent advances in targeted therapies, the molecular mechanisms driving breast cancer initiation, progression, and metastasis are minimally understood. Growing evidence indicate that transfer RNA (tRNA)-derived small RNAs (tsRNA) contribute to biological control and aberrations associated with cancer development and progression. The runt-related transcription factor 1 (RUNX1) transcription factor is a tumor suppressor in the mammary epithelium whereas RUNX1 downregulation is functionally associated with breast cancer initiation and progression. We identified four tsRNA (ts-19, ts-29, ts-46, and ts-112) that are selectively responsive to expression of the RUNX1 tumor suppressor. Our finding that ts-112 and RUNX1 anticorrelate in normal-like mammary epithelial and breast cancer lines is consistent with tumor-related activity of ts-112 and tumor suppressor activity of RUNX1. Inhibition of ts-112 in MCF10CA1a aggressive breast cancer cells significantly reduced proliferation. Ectopic expression of a ts-112 mimic in normal-like mammary epithelial MCF10A cells significantly increased proliferation. These findings support an oncogenic potential for ts-112. Moreover, RUNX1 may repress ts-112 to prevent overactive proliferation in breast epithelial cells to augment its established roles in maintaining the mammary epithelium.

Central aspects of systemic oestradiol negative- and positive-feedback on the reproductive neuroendocrine system.

The central nervous system regulates fertility via the release of gonadotrophin-releasing hormone (GnRH). This control revolves around the hypothalamic-pituitary-gonadal axis, which operates under traditional homeostatic feedback by sex steroids from the gonads in males and most of the time in females. An exception is the late follicular phase in females, when homeostatic feedback is suspended and a positive-feedback response to oestradiol initiates the preovulatory surges of GnRH and luteinising hormone. Here, we briefly review the history of how mechanisms underlying central control of ovulation by circulating steroids have been studied, discuss the relative merit of different model systems and integrate some of the more recent findings in this area into an overall picture of how this phenomenon occurs.

Estradiol Enhances the Depolarizing Response to GABA and AMPA Synaptic Conductances in Arcuate Kisspeptin Neurons by Diminishing Voltage-Gated Potassium Currents.

Synaptic and intrinsic properties interact to sculpt neuronal output. Kisspeptin neurons in the hypothalamic arcuate nucleus help convey homeostatic estradiol feedback to central systems controlling fertility. Estradiol increases membrane depolarization induced by GABAA receptor activation in these neurons. We hypothesized that the mechanisms underlying estradiol-induced alterations in postsynaptic response to GABA, and also AMPA, receptor activation include regulation of voltage-gated potassium currents. Whole-cell recordings of arcuate kisspeptin neurons in brain slices from ovariectomized (OVX) and OVX+estradiol (OVX+E) female mice during estradiol negative feedback revealed that estradiol reduced capacitance, reduced transient and sustained potassium currents, and altered voltage dependence and kinetics of transient currents. Consistent with these observations, estradiol reduced rheobase and action potential latency. To study more directly interactions between synaptic and active intrinsic estradiol feedback targets, dynamic clamp was used to simulate GABA and AMPA conductances. Both GABA and AMPA dynamic clamp-induced postsynaptic potentials (PSPs) were smaller in neurons from OVX than OVX+E mice; blocking transient potassium currents eliminated this difference. To interrogate the role of the estradiol-induced changes in passive intrinsic properties, different Markov model structures based on the properties of the transient potassium current in cells from OVX or OVX+E mice were combined in silico with passive properties reflecting these two endocrine conditions. Some of tested models reproduced the effect on PSPs in silico, revealing that AMPA PSPs were more sensitive to changes in capacitance. These observations support the hypothesis that PSPs in arcuate kisspeptin neurons are regulated by estradiol-sensitive mechanisms including potassium conductances and membrane properties.SIGNIFICANCE STATEMENT Kisspeptin neurons relay estradiol feedback to gonadotropin-releasing hormone neurons, which regulate the reproductive system. The fast synaptic neurotransmitters GABA and glutamate rapidly depolarize arcuate kisspeptin neurons and estradiol increases this depolarization. Estradiol reduced both potassium current in the membrane potential range typically achieved during response to fast synaptic inputs and membrane capacitance. Using simulated GABA and glutamate synaptic inputs, we showed changes in both the passive and active intrinsic properties induced by in vivo estradiol treatment affect the response to synaptic inputs, with capacitance having a greater effect on response to glutamate. The suppression of both passive and active intrinsic properties by estradiol feedback thus renders arcuate kisspeptin neurons more sensitive to fast synaptic inputs.

Changes in Both Neuron Intrinsic Properties and Neurotransmission Are Needed to Drive the Increase in GnRH Neuron Firing Rate during Estradiol-Positive Feedback.

Central output of gonadotropin-releasing hormone (GnRH) neurons controls fertility and is sculpted by sex-steroid feedback. A switch of estradiol action from negative to positive feedback initiates a surge of GnRH release, culminating in ovulation. In ovariectomized mice bearing constant-release estradiol implants (OVX+E), GnRH neuron firing is suppressed in the morning (AM) by negative feedback and activated in the afternoon (PM) by positive feedback; no time-of-day-dependent changes occur in OVX mice. In this daily surge model, GnRH neuron intrinsic properties are shifted to favor increased firing during positive feedback. It is unclear whether this shift and the observed concomitant increase in GABAergic transmission, which typically excites GnRH neurons, are independently sufficient for increasing GnRH neuron firing rate during positive feedback or whether both are needed. To test this, we used dynamic clamp to inject selected previously recorded trains of GABAergic postsynaptic conductances (PSgs) collected during the different feedback states of the daily surge model into GnRH neurons from OVX, OVX+E AM, and OVX+E PM mice. PSg trains mimicking positive feedback initiated more action potentials in cells from OVX+E PM mice than negative feedback or OVX (open feedback loop) trains in all three animal models, but the positive-feedback train was most effective when applied to cells during positive feedback. In silico studies of model GnRH neurons in which >1000 PSg trains were tested exhibited the same results. These observations support the hypothesis that GnRH neurons integrate fast-synaptic and intrinsic changes to increase firing rates during positive feedback.SIGNIFICANCE STATEMENT Infertility affects 15%-20% of couples; failure to ovulate is a common cause. Understanding how the brain controls ovulation is critical for new developments in both infertility treatment and contraception. Ovarian estradiol alters both the intrinsic properties of gonadotropin-releasing hormone (GnRH) neurons and synaptic inputs to these cells coincident with production of sustained GnRH release that ultimately triggers ovulation. We demonstrate here using dynamic clamp and mathematical modeling that estradiol-induced shifts in synaptic transmission alone can increase firing output, but that the intrinsic properties of GnRH neurons during positive feedback further poise these cells for increased response to higher frequency synaptic transmission. These data suggest that GnRH neurons integrate fast-synaptic and intrinsic changes to increase firing rates during the preovulatory GnRH surge.

Changes in GABAergic Transmission to and Intrinsic Excitability of Gonadotropin-Releasing Hormone (GnRH) Neurons during the Estrous Cycle in Mice.

Gonadotropin-releasing hormone (GnRH) neurons form the final common central output pathway controlling fertility and are regulated by steroid feedback. In females, estradiol feedback action varies between negative and positive; negative feedback typically regulates episodic GnRH release whereas positive feedback initiates a surge of GnRH, and subsequently luteinizing hormone (LH) release ultimately triggering ovulation. During the estrous cycle, changes between estradiol negative and positive feedback occur with cycle stage and time of day, with positive feedback in the late afternoon of proestrus in nocturnal species. To test the hypotheses that synaptic and intrinsic properties of GnRH neurons are regulated by cycle stage and time of day, we performed whole-cell patch-clamp studies of GnRH neurons in brain slices from mice at two times considered negative feedback (diestrous PM and proestrous AM) and during positive feedback (proestrous PM). GABAergic transmission can excite GnRH neurons and was higher in cells from proestrous PM mice than cells from proestrous AM mice and approached traditional significance levels relative to cells from diestrous PM mice. Action potential response to current injection was also greater in cells from proestrous PM mice than the other two groups. Interestingly, the hormonal milieu of proestrous AM provided stronger negative feedback on both GnRH neuron excitability and GABAergic postsynaptic current (PSC) amplitude than diestrous PM. These observations demonstrate elements of both synaptic and intrinsic properties of GnRH neurons are regulated in a cycle-dependent manner and provide insight into the neurobiological mechanisms underlying cyclic changes in neuroendocrine function among states of estradiol negative and positive feedback.

Gonadotropin-Releasing Hormone (GnRH) Neuron Excitability Is Regulated by Estradiol Feedback and Kisspeptin.

Gonadotropin-releasing hormone (GnRH) neurons produce the central output controlling fertility and are regulated by steroid feedback. A switch from estradiol negative to positive feedback initiates the GnRH surge, ultimately triggering ovulation. This occurs on a daily basis in ovariectomized, estradiol-treated (OVX+E) mice; GnRH neurons are suppressed in the morning and activated in the afternoon. To test the hypotheses that estradiol and time of day signals alter GnRH neuron responsiveness to stimuli, GFP-identified GnRH neurons in brain slices from OVX+E or OVX female mice were recorded during the morning or afternoon. No differences were observed in baseline membrane potential. Current-clamp revealed GnRH neurons fired more action potentials in response to current injection during positive feedback relative to all other groups, which were not different from each other despite reports of differing ionic conductances. Kisspeptin increased GnRH neuron response in cells from OVX and OVX+E mice in the morning but not afternoon. Paradoxically, excitability in kisspeptin knock-out mice was similar to the maximum observed in control mice but was unchanged by time of day or estradiol. A mathematical model applying a Markov Chain Monte Carlo method to estimate probability distributions for estradiol- and time of day-dependent parameters was used to predict intrinsic properties underlying excitability changes. A single identifiable distribution of solutions accounted for similar GnRH neuron excitability in all groups other than positive feedback despite different underlying conductance properties; this was attributable to interdependence of voltage-gated potassium channel properties. In contrast, redundant solutions may explain positive feedback, perhaps indicative of the importance of this state for species survival.SIGNIFICANCE STATEMENT Infertility affects 15%-20% of couples; failure to ovulate is a common cause. Understanding how the brain controls ovulation is critical for new developments in both infertility treatment and contraception. Gonadotropin-releasing hormone (GnRH) neurons are the final common pathway for central neural control of ovulation. We studied how estradiol feedback regulates GnRH excitability, a key determinant of neural firing rate using laboratory and computational approaches. GnRH excitability is upregulated during positive feedback, perhaps driving increased neural firing rate at this time. Kisspeptin increased GnRH excitability and was essential for estradiol regulation of excitability. Modeling predicts that multiple combinations of changes to GnRH intrinsic conductances can produce the firing response in positive feedback, suggesting the brain has many ways to induce ovulation.

Coping with workplace minority stress: Associations between dyadic coping and anxiety among women in same-sex relationships.

Sexual minorities are exposed to stressors in the workplace (workplace minority stress), which can be detrimental for well-being (e.g., levels of anxiety). The present study examined whether a particular set of relationship processes, dyadic coping, served to moderate the association between workplace minority stress and symptoms of anxiety. Using a dyadic sample of 64 female same-sex couples, we found that partner problem-focused supportive dyadic coping (DC) and emotion-focused supportive DC (marginally) buffered, whereas partner delegated DC and negative DC did not moderate, the association between workplace minority stress and symptoms of anxiety. Implications for relationship researchers and mental health practitioners are discussed.

Apoptosis inhibitor TRIAP1 is a novel effector of drug resistance.

TP53-regulated inhibitor of apoptosis 1 (TRIAP1) is a novel apoptosis inhibitor that binds HSP70 in the cytoplasm and blocks the formation of the apoptosome and caspase-9 activation. TRIAP1 has been shown to be upregulated in many types of cancers; however, its role remains elusive. We determined the TRIAP1 mRNA levels in a panel of human tissues and found its expression to be ubiquitous. Normal breast, as well as non-tumorigenic breast cells, exhibited lower TRIAP1 mRNA levels than breast cancer cells or their drug-resistant derivatives. TRIAP1 is a small, evolutionarily conserved protein that is 76 amino acids long. We found that yeast cells, in which the TRIAP1 homologue was knocked out, had increased sensitivity to doxorubicin. Equally, RNA interference in breast cancer drug-resistant cells demonstrated that downregulation of TRIAP1 impaired cell growth in the presence of doxorubicin. As expected, caspase-9 activation was diminished after overexpression of TRIAP1 in drug-resistant cells. Importantly, stable transfections of a TRIAP1 expression plasmid in CAL51 cells led to a marked increase in the number of doxorubicin-resistant clones, that was abolished when cells expressed hairpins targeting TRIAP1. In addition, we showed that TRIAP1 expression was also triggered by estrogen deprivation in MCF-7 cells. Although both polyclonal and monoclonal antibodies generated for the present study failed to robustly detect TRIAP1, we demonstrated that TRIAP1 represents a novel marker for drug resistance in breast cancer cells and it may be used in the stratification of breast cancer patients once a suitable antibody has been developed. Equally, these studies open potential drug development strategies for blocking TRIAP1 activity and avoiding drug resistance.

Low frequency paternal transmission of plastid genes in Brassicaceae.

Plastid-encoded genes are maternally inherited in most plant species. Transgenes located on the plastid genome are thus within a natural confinement system, preventing their distribution via pollen. However, a low-frequency leakage of plastids via pollen seems to be universal in plants. Here we report that a very low-level paternal inheritance in Arabidopsis thaliana occurs under field conditions. As pollen donor an Arabidopsis accession (Ler-Ely) was used, which carried a plastid-localized atrazine resistance due to a point mutation in the psbA gene. The frequency of pollen transmission into F1 plants, based on their ability to express the atrazine resistance was 1.9 × 10(-5). We extended our analysis to another cruciferous species, the world-wide cultivated crop Brassica napus. First, we isolated a fertile and stable plastid transformant (T36) in a commercial cultivar of B. napus (cv Drakkar). In T36 the aadA and the bar genes were integrated in the inverted repeat region of the B. napus plastid DNA following particle bombardment of hypocotyl segments. Southern blot analysis confirmed transgene integration and homoplasmy of plastid DNA. Line T36 expressed Basta resistance from the inserted bar gene and this trait was used to estimate the frequency of pollen transmission into F1 plants. A frequency of <2.6 × 10(-5) was determined in the greenhouse. Taken together, our data show a very low rate of paternal plastid transmission in Brassicacea. Moreover, the establishment of plastid transformation in B. napus facilitates a safe use of this important crop plant for plant biotechnology.

Loss of O6-methylguanine-DNA methyltransferase confers collateral sensitivity to carmustine in topoisomerase II-mediated doxorubicin resistant triple negative breast cancer cells.

Triple-negative breast cancer is characterized by aggressive tumours whose cells lack oestrogen and progesterone receptors and do not over-express HER2. It accounts for approximately 10-15% of breast cancer cases. We sought to generate a cellular model of chemotherapy drug resistance for this type of disease to provide the tools for the development of new therapies. Doxorubicin is a component of some chemotherapy regimes used to treat this form of cancer but resistance preventing disease eradication frequently occurs, mainly due to over-expression of drug transporters such as P-glycoprotein. CALDOX cells were generated by exposure of CAL51 to doxorubicin. Resistance to doxorubicin did not involve drug transporters, as the both parental and resistant cells accumulated doxorubicin to comparable levels. CALDOX cells had slower proliferation rate and an extended G1 cell cycle stage than the parental line, mainly due to an intrinsic activation of CDNK1 (p21), but this cell cycle block was not involved in the mechanism of resistance. CALDOX cells had reduced levels of TOP2A (topoisomerase IIα) and were cross resistant to the topoisomerase II inhibitors etoposide and mitoxantrone. CALDOX cells showed collateral sensitivity to carmustine due to the lack of O6-methylguanine-DNA-methyltransferase (MGMT) expression, related to the hypermethylation of its promoter. The collateral sensitivity of CALDOX cells to carmustine provides the rationale to evaluate MGMT promoter methylation status to design better therapeutic strategies for triple negative breast cancer.

Plasma HHV8 DNA predicts relapse in individuals with HIV-associated multicentric Castleman disease.

HIV-associated multicentric Castleman disease (HIV-MCD) is a rare lymphoproliferative disorder caused by infection with human herpesvirus-8. The disease follows a relapsing and remitting clinical course, with marked systemic symptoms during an active attack, which can prove fatal. Its incidence is rising, and new data indicate the utility of the anti-CD20 monoclonal antibody rituximab at inducing remissions in both first- and second-line settings, although biomarkers associated with relapse have not been previously identified. In 52 individuals with a histologic diagnosis of HIV-MCD, we performed univariate and multivariate analyses to predict factors associated with an HIV-MCD attack. Although a younger age (< 50 years) was associated with an attack, the strongest association was observed with plasma levels of human herpesvirus-8 DNA. Rising levels predicted an attack (hazard ratio = 2.9; 95% confidence interval, 1.3-6.7), and maintenance therapy with rituximab should be considered in these individuals.

High heritability of speech and language impairments in 6-year-old twins demonstrated using parent and teacher report.

Previous twin studies have demonstrated high heritability of specific language impairment (SLI) when the diagnosis is based on psychometric testing. The current study measured the effectiveness of parent and teacher ratings of communication skills in identifying heritable language impairment. The Children's Communication Checklist was completed by parents and teachers of 6-year-old twins recruited from a general population sample. One hundred and thirty twin pairs (65 MZ) were selected because at least one twin had low language skills at 4 years of age; a further 66 pairs (37 MZ) were a low risk group with no indication of language difficulties at 4 years. Internal consistency, inter-rater reliability, and validity in identifying language impairment were assessed for all CCC scales. CCC scales, especially those assessing structural language skills, were highly effective in identifying cases of language impairment, but agreement between parent and teacher ratings was modest. Genetic analysis revealed negligible environmental influence and substantial genetic influence on most scales. A rater-specific effects model was fit to the data to assess how far parents and teachers assess a common genetic factor on the CCC. Ratings of parents and teachers were influenced to some extent by the same child characteristics, but rater-specific effects were also evident, especially on scales measuring pragmatic aspects of communication. This study shows that there are strong genetic influences on both structural and pragmatic language impairments in children, and these can be detected using a simple checklist completed by parents or teachers.

Measurement of cerebrovascular flow reserve in pediatric patients with sickle cell disease.

PURPOSE: To report a method for determining absolute percentage change in cerebral blood flow (measurement of cerebrovascular reserve) before and after acetylazolamide (Diamox) administration in children with sickle cell anemia. MATERIALS AND METHODS: Thirty-six symptomatic sickle cell disease patients (48 studies) were evaluated. After the injection of either Tc-99m bicisate ethyl cysteinate dimer (ECD) or hexamethyl propylene amine oxime (HMPAO), both whole body scans (with geometric mean correction) and single photon emission computed tomography (CT) were performed pre- and post-Diamox administration with calculation of percentage brain uptake on the whole body images for both examinations and determination of cerebrovascular reserve (percentage change in brain uptake post-Diamox). Evaluation for regional cerebral perfusion change was also performed. RESULTS: The cerebrovascular reserve measurement was 17.6% +/- 43.5% (mean +/- 1 SD). Thirty-three of 48 studies (69%) showed an abnormal cerebrovascular reserve, while only 6 of 48 studies (12.5%) showed Diamox-induced regional perfusion changes in the brain. No statistically significant relationship was found between the occurrence of a regional perfusion abnormality versus loss of cerebrovascular reserve (P = 0.75, Fisher exact test), suggesting that these are independent variables. The cerebrovascular reserve was reproducible, with an average standard deviation of +/-0.54%. CONCLUSION: A new, simple method for calculation of cerebrovascular reserve is presented; this method is reproducible and appears to be an independent variable in the evaluation of cerebrovascular status in sickle cell anemia patients. It should allow further characterization of this complex patient population, and possibly assist in detection of patients at risk for developing "silent" or overt stroke.