Evidence for an Association of the Dopamine D5 Receptor Gene on Age at Onset of Attention Deficit Hyperactivity Disorder

The purpose of this study was to determine whether the single nucleotide polymorphisms (SNPs) within candidate genes for attention deficit hyperactivity disorder (ADHD) are associated with the age at onset for ADHD. One hundred and forty-three SNPs were genotyped across five candidate genes ( DRD5 , SLC6A3 , HTR1B , SNAP25 , DRD4 ) for ADHD in 229 families with at least one affected offspring. SNPs with the highest estimated power to detect an association with age at onset were selected for each candidate gene, using a power-based screening procedure that does not compromise the nominal significance level. A time-to-onset analysis for family-based samples was performed on these SNPs to determine if an association exists with age at onset for ADHD. Seven consecutive SNPs surrounding the D5 dopamine receptor gene ( DRD5 ), were associated with the age at onset for ADHD; FDR adjusted q-values ranged from 0.008 to 0.023. This analysis indicates that individuals with the risk genotype develop ADHD earlier than individuals with any other genotype. A haplotype analysis across the 6 significant SNPs that were in linkage disequilibrium with one another, CTCATA , was also found to be significant (p-value = 0.02). We did not observe significant associations with age at onset for the other candidate loci tested. Although definitive conclusions await independent replication, these results suggest that a variant in DRD5 may affect age at onset for ADHD.     

The Sydney AFF Score: A Simple Tool to Distinguish Females Presenting With Atypical Femur Fractures Versus Typical Femur Fractures

Atypical femur fractures (AFF) are a rare but serious complication of long-term bisphosphonate use. Although clearly defined by ASBMR criteria, a proportion of patients with AFFs may go unrecognized and the use of qualitative fracture criteria may lead to uncertainty in AFF diagnosis, with significant therapeutic implications. A score that rapidly and accurately identifies AFFs among subtrochanteric femur fractures using quantitative, measurable parameters is needed. In a retrospective cohort of 110 female patients presenting with AFFs or typical femur fractures (TFFs), multiple logistic regression and decision tree analysis were used to develop the Sydney AFF score. This score, based on demographic and femoral geometry variables, uses three dichotomized independent predictors and adds one point for each: (age ≤80 years) + (femoral neck width <37 mm) + (lateral cortical width at lesser trochanter ≥5 mm), (score, 0 to 3). In an independent validation set of 53 female patients at a different centre in Sydney, a score ≥2 demonstrated 73.3% sensitivity and 69.6% specificity for AFF (area under the receiver-operating characteristic curve [AUC] 0.775, SE 0.063) and remained independently associated with AFF after adjustment for bisphosphonate use. The Sydney AFF score provides a quantitative means of flagging female patients with atraumatic femur fractures who have sustained an AFF as opposed to a TFF. This distinction has clear management implications and may augment current ASBMR diagnostic criteria. © 2021 American Society for Bone and Mineral Research (ASBMR).     

The burden of cutaneous disease in solid organ transplant recipients of color

Organ transplant recipients (OTRs) are at increased risk of cutaneous malignancy. Skin disorders in OTRs of color (OTRoC) have rarely been systematically assessed. We aimed to ascertain the burden of skin disease encountered in OTRoC by prospectively collecting data from OTRs attending 2 posttransplant skin surveillance clinics: 1 in London, UK and 1 in Philadelphia, USA. Retrospective review of all dermatological diagnoses was performed. Data from 1766 OTRs were analyzed: 1024 (58%) white, 376 (21%) black, 261 (15%) Asian, 57 (3%) Middle Eastern/Mediterranean (ME/M), and 48 (2.7%) Hispanic; and 1128 (64%) male. Viral infections affected 45.1% of OTRs, and were more common in white and ME/M patients (P < .001). Fungal infections affected 28.1% and were more common in ME/M patients (P < .001). Inflammatory skin disease affected 24.5%, and was most common in black patients (P < .001). In addition, 26.4% of patients developed skin cancer. There was an increased risk of skin cancer in white vs nonwhite OTRs (HR 4.4, 95% CI 3.5-5.7, P < .001): keratinocyte cancers were more common in white OTRs (P < .001) and Kaposi sarcoma was more common in black OTRs (P < .001). These data support the need for programs that promote targeted dermatology surveillance for all OTRs, regardless of race/ethnicity or country of origin.     

Partners’ Consensus About Joint Effort and COVID-19 Prevention Among Sexual Minority Men

The current study examined the relevance of relationship functioning to partners’ agreement or consensus about joint effort surrounding COVID-19 prevention. Interdependence theory has been widely used to understand how relationship partners influence health behavior, including how sexual minority male (SMM) couples regulate HIV risk. Couples with better relationship functioning tend to be more successful at negotiating joint (shared) goals and subsequently accomplishing them. The study recruited 134 cis-male, SARS-CoV-2 negative adults in relationships with cis-male partners from phone-based social networking applications. Participants completed an online survey assessing relationship functioning (Perceived Relationship Components Questionnaire), COVID-19 prevention behaviors, and risk perceptions. Partners’ consensus around joint COVID-19 prevention effort was assessed using an adapted version of the Preferences for Sexual Health Outcomes scale. Path analyses indicated that consensus for joint prevention effort predicted social distancing (B?=?0.23; p?=?.001) and the number of other COVID-19 prevention behaviors engaged in (B?=?0.17; p?=?.003) above and beyond perceived risk and relationship functioning. Relationship satisfaction predicted higher levels of consensus for joint COVID-19 prevention effort (B?=?0.40; p?=?.029). Findings suggest that the theoretical foundations of successful HIV prevention interventions that utilize joint goal formation may generalize to the prediction of COVID-19 prevention behavior and may be leveraged to mitigate the risk of SARS-CoV-2 infection among SMM in relationships. Interventions that overlook the potential for dyadic regulation of health behavior may miss opportunities to capitalize on shared coping resources and fail to address relational barriers to prevention.

     

Further studies on the antinociceptive effects ofΔ acid

The antinociceptive effects of (THC-7-oic) acid have been investigated further with particular regard to the influence of certain experimental parameters in the hot plate test. These included the degree of the thermal stimulus, the nature of the vehicle and a possible role for copper in the response. A temperature effect similar to that seen with nonsteroidalantiinflammatory drugs (NSAIDs) was observed, 55° produced observable antinociception, however, at a surface temperature of 58°C no drug effect was seen. Non-aqeous vehicles such as peanut oil increased the potency of THC-7-oic acid. Finally, the substitution of purified water for tap water reduced,the drug response which could be partially restored by adding copper to the purified drinking water. An increase in the inhibitory effect when copper was added was also seenin vitro in a cell culture model where the acid reduced prostaglandin synthesis induced by THC. Our findings suggest that THC-7-oic acid probably acts by mechanisms similar to the NSAIDs and that the above mentioned experimental conditions can greatly influence the outcome of studies with this agent.     

Multiple origins of polyploids in the Glycine tabacina complex inferred from chloroplast DNA polymorphism

The Glycine tabacina polyploid complex has been shown to include a minimum of two morphological and crossing groups, which also differ in chloroplast DNA (cpDNA) restriction map and nuclear ribosomal gene repeat phenotype. These AAB2B2 and BBB2B2 G. tabacina polyploids contain plastomes referable to the A and B diploid plastome groups of subgenus Glycine, respectively. Eight different cpDNA variants were observed among the 65 B-type polyploids studied, six of which were identical for numerous restriction site characters to plastome types found among the highly polymorphic B genome diploid species. It is hypothesized that there have been numerous independent origins of polyploid G. tabacina: at least one AA x B2B2 event and a minimum of five BB x B2B2 events involving different BB types as female progenitor. Low amounts of cpDNA divergence between diploid and polyploid plastomes and among the plastomes of geographically disjunct polyploids suggest that the origin and dispersal of polyploids are relatively recent events. All hypothesized diploid progenitors are native to Australia, while both A- and B-type G. tabacina polyploids occur on islands of the Pacific outside the range of diploids. The presence of several different plastome types of polyploid G. tabacina in the Pacific islands suggests that several colonization events have occurred.     

Serotonin antagonists and vascular protection

Summary There is very suggestive evidence for a role of serotonin release from platelets in the mechanisms for platelet aggregation, arterial thrombosis, and arterial spasm. These effects are mediated via the 5HT₂ receptor and are specifically antagonized by ketanserin. The recently published PACK study was a randomized controlled trial of the effects of ketanserin in patients with intermittent claudication. The purpose of the trial was to discover whether ketanserin treatment would reduce the incidence of atherosclerotic complications such as myocardial infarction or stroke. An unexpected adverse interaction between ketanserin and potassium-losing diuretics was observed, causing an excess of deaths in the group taking this combination of drugs. The intention-to-treat analysis showed no overall difference between ketanserin and placebo in terms of cardiovascular complications. Withdrawal of patients taking potassium-losing diuretics left insufficient numbers of patients in the study to answer the original question. However, the on-treatment analysis excluding those taking the combination suggested strongly, although did not prove, that ketanserin reduced thrombotic episodes by about 25%. It is concluded that the risks of interactions between many drugs and potassium-losing diuretics make the use of the latter undesirable. Further studies on ketanserin, possibly combined with thromboxane A₂ inhibitors, seem highly desirable.     

An evaluation of the Australian government's policy of access and equity strategy in selected localities

Australia is a country of 17 million people from diverse cultural and racial backgrounds. To respond to this diversity, the Australian Commonwealth Government in 1986 announced an Access and Equity Strategy as part of the Agenda for a Multicultural Australia. The Strategy was evaluated in 1991, and included five locality studies which assessed the implementation of the Strategy from the perspective of target groups of Aboriginal and non-English speaking people (NESB). This article describes this evaluation and the development of the Australian multicultural policy within which the Strategy is conceived. The findings and recommendations from the locality studies provide case examples of government wide policy development and implementation processes.