Intellectual Disability Related to De Novo Germline Loss of the Distal End of the P-Arm of Chromosome 17: A Case Report

Hypothesis/Purpose: In this report we present a case of a 20-year-old female with congenital intellectual disability, stunted growth, and hypothyroidism. Competitive genetic hybridization (CHG) revealed a loss of 17p13.3, and the deletion was not present in either parent. This deletion has not previously been characterized, but mutations on the p-arm of chromosome 17 are responsible for Miller-Dieker Syndrome and Isolated Lissencephaly Sequence, both of which share symptoms in common with the patient. Methods: Peripheral mononuclear cells (PBMCs) were used for karyotyping and competitive genetic hybridization (CHG). Bioinformatic analysis was carried out using the Genome Data Viewer (ncbi.nlm.nih.gov/genome/gdv). Results: Karyotype was found to be normal, but CGH revealed a deletion of the tail end of the p-arm of chromosome 17, 17p13.3. At least 134 genes are present in this genomic location, and 35 of them are uncharacterized. Both Miller-Dieker Syndrome (MDS) and Isolated Lissencephaly Sequence (ILS) are characterized by a smooth cerebral cortex and intellectual disability, but the patient’s symptoms more closely mirror MDS because muscle tone was normal. The patient was significantly shorter than peers, but growth hormone therapy over the course of several years allowed the patient to reach a normal height, albeit shorter than her siblings and parents. The list of genes deleted will be investigated to determine if a single gene is likely responsible for the phenotype. Conclusions: Here we present a patient with intellectual disability and a previously uncharacterized deletion on chromosome 17. Similar, though not identical conditions have been previously reported, but not well characterized indicating that the present patient could possibly have one of these conditions. Further directions include investigation of the deleted genes to determine a probable cause for the symptoms exhibited

Exploring Glucose Dysregulation in Migraine: Insights from Continuous Glucose Monitoring

Despite being associated with hypoglycemia for nearly a century, a definitive relationship between migraines and glucose dysregulation remains elusive. Accumulating evidence suggests that migraines are in part due to a metabolic mismatch between cerebral demand and available energy. Research analyzing plasma glucose levels and migraine activity may further elucidate this interface between metabolic dysregulation and migraine pathophysiology and may potentially open avenues for therapeutic interventions targeting holistic metabolism for migraine management

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Single- and Multiple-Dose Pharmacokinetics of Darunavir Plus Ritonavir and Etravirine in Semen and Rectal Tissue of HIV-Negative Men

Antiretroviral therapy (ART) has become a central component of combination HIV prevention efforts. Defining the individual exposure of commercially available ART in genital secretions and vulnerable mucosal tissues is paramount to designing future prevention interventions

Immunogenicity of COVID ‐19 vaccines in patients with follicular lymphoma receiving frontline chemoimmunotherapy

Summary: Immune responses to primary COVID‐19 vaccination were investigated in 58 patients with follicular lymphoma (FL) as part of the PETReA trial of frontline therapy (EudraCT 2016–004010‐10). COVID‐19 vaccines (BNT162b2 or ChAdOx1) were administered before, during or after cytoreductive treatment comprising rituximab (depletes B cells) and either bendamustine (depletes CD4+ T cells) or cyclophosphamide‐based chemotherapy. Blood samples obtained after vaccine doses 1 and 2 (V1, V2) were analysed for antibodies and T cells reactive to the SARS‐CoV‐2 spike protein using the Abbott Architect and interferon‐gamma ELISpot assays respectively. Compared to 149 healthy controls, patients with FL exhibited lower antibody but preserved T‐cell responses. Within the FL cohort, multivariable analysis identified low pre‐treatment serum IgA levels and V2 administration during induction or maintenance treatment as independent determinants of lower antibody and higher T‐cell responses, and bendamustine and high/intermediate FLIPI‐2 score as additional determinants of a lower antibody response. Several clinical scenarios were identified where dichotomous immune responses were estimated with >95% confidence based on combinations of predictive variables. In conclusion, the immunogenicity of COVID‐19 vaccines in FL patients is influenced by multiple disease‐ and treatment‐related factors, among which B‐cell depletion showed differential effects on antibody and T‐cell responses

Feminist Economics, Setting out the Parameters

___Introduction___ Feminist economics has developed its position over the past decade, towards a firmer embeddedness in economic science and a source of inspiration for activists, policy makers, and social science researchers in a wide variety of fields of research. This development has come about in a relatively short period of time, as is reflected, for example, in the follow-up book of the feminist economic primer Beyond Economic Man (Ferber/Nelson 1993), published ten years later: Feminist Economics Today (Ferber/Nelson, 2003) The strengthened position of feminist economics also shows in the 10-year anniversary of the prize-winning journal Feminist Economics, the flourishing of the International Association for Feminist Economics (IAFFE), as well as the more regular demand for feminist economic policy advise by institutions like the UN, OECD and governments in developed and developing countries, and in well-established training courses in feminist economics, such as at the Institute of Social Studies and University of Utah . It is impossible to give a fair overview of the state of the art of feminist economics in the number of pages available, even when limited to issues pertaining to development and macroeconomics . As a consequence, this is a very sketchy and subjective overview of what I perceive to be recent developments in feminist economics that have relevance for feminist development analysis and policy. The next section recognizes three trends in feminist economics, in particular the engagement of feminist economists with heterodox schools of economics. The following sections will briefly review developments in methodology and methods in feminist economics. These will be followed by three sections on topics that have recently become key themes or areas of research in feminist economics, in particular in the area of development economics: unpaid labour and the care economy; the two-way relationship between gender and trade; and gender, efficiency and growth. Each of these topics will be introduced, with references to the main literature, and some links to policy recommendations. The paper will end with a conclusion

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Indigenous Peoples and research: self-determination in research governance

Indigenous Peoples are reimagining their relationship with research and researchers through greater self-determination and involvement in research governance. The emerging discourse around Indigenous Data Sovereignty has provoked discussions about decolonizing data practices and highlighted the importance of Indigenous Data Governance to support Indigenous decision-making and control of data. Given that much data are generated from research, Indigenous research governance and Indigenous Data Governance overlap. In this paper, we broaden the concept of Indigenous Data Sovereignty by using the CARE Principles for Indigenous Data Governance to discuss how research legislation and policy adopted by Indigenous Peoples in the US set expectations around recognizing sovereign relationships, acknowledging rights and interests in data, and enabling Indigenous Peoples' participation in research governance