Treatment-resistant depression: molecular mechanisms and management.

Due to the heterogeneous nature of depression, the underlying etiological mechanisms greatly differ among individuals, and there are no known subtype-specific biomarkers to serve as precise targets for therapeutic efficacy. The extensive research efforts over the past decades have not yielded much success, and the currently used first-line conventional antidepressants are still ineffective for close to 66% of patients. Most clinicians use trial-and-error treatment approaches, which seem beneficial to only a fraction of patients, with some eventually developing treatment resistance.

RECOVER-NEURO: study protocol for a multi-center, multi-arm, phase 2, randomized, active comparator trial evaluating three interventions for cognitive dysfunction in post-acute sequelae of SARS-CoV-2 infection (PASC).

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) symptoms have broad impact, and may affect individuals regardless of COVID-19 severity, socioeconomic status, race, ethnicity, or age. A prominent PASC symptom is cognitive dysfunction, colloquially referred to as "brain fog" and characterized by declines in short-term memory, attention, and concentration. Cognitive dysfunction can severely impair quality of life by impairing daily functional skills and preventing timely return to work.

Neuropsychological normative standards for late career physicians.

In the context of an aging, vital physician workforce, there is clear value in establishing a specialized neuropsychological normative dataset for the evaluation of late career physicians practicing clinical medicine. Physicians aged 60 and over in active clinical practice at 3 major medical centers in North Carolina were recruited to complete a comprehensive neuropsychological test battery. The sample ( = 100) was aged 60-78.

Depression following small vessel stroke is common and more prevalent in women.

Objectives: We sought to examine the frequency of depression after small vessel-type stroke (SVS) and associated risk factors.

Materials And Methods: We conducted a retrospective analysis of a prospective cohort of patients enrolled in the American Stroke Association-Bugher SVS Study, which included 200 participants within 2-years of SVS and 79 controls without a history of stroke from 2007 to 2012 at four sites. The primary outcome was PHQ-8, with scores ≥10 consistent with post-stroke depression (PSD).

Epilepsy among the older population of sub-Saharan Africa: Analysis of the global burden of disease database.

Introduction: Epilepsy is considered one of the most burdensome neurologic diseases by the World Health Organization due to the high risk of morbidity and mortality. Few studies have investigated the epidemiology of idiopathic epilepsy in Sub-Saharan Africa (SSA). This study aims to characterize the disease burden of epilepsy among the older population in SSA via a large international database.

A prospective randomized study examining the impact of intravenous versus inhalational anesthesia on postoperative cognitive decline and delirium.

The present prospective randomized study was designed to investigate whether the development of Post Operative Cognitive Decline (POCD) is related to anesthesia type in older adults. All patients were screened for delirium and mental status, received baseline neuropsychological assessment, and evaluation of activities of daily living (ADLs). Follow-up assessments were performed at 3-6 months and 12-18 months.

"Walking the Journey Together": Creating a unique learning module in provider-patient communication for the care of epilepsy in Uganda.

Objective: This report documents the creation of a practical communication skills module about epilepsy care, specifically targeted at first-line care providers who treat patients with epilepsy in Uganda.

Methods: Our team conducted semi-structured interviews, utilizing Zoom video conferencing, with Ugandan physicians specializing in epilepsy care. Our interview guide promoted a semi-structured conversational interview that explored aspects related to developing a patient-provider relationship, how epilepsy is described in a culturally appropriate manner, exploration of alternative treatments, the impact of the stigma of epilepsy, and facilitators and barriers to antiepileptic drug treatment adherence.

Evaluation of a tailored epilepsy training program for healthcare providers in Uganda.

Objective: This study evaluated an epilepsy training program for healthcare workers that was designed to improve their knowledge of epilepsy, its treatment, and its psychosocial effects.

Methods: This single group, before and after survey was conducted in three regional referral hospitals in Uganda. Healthcare workers participated in a 3-day epilepsy training program and were assessed immediately prior to and following the program using a 39-item epilepsy knowledge questionnaire.

Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics.

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets.

COVID-19-Associated Guillain-Barre Syndrome: Atypical Para-infectious Profile, Symptom Overlap, and Increased Risk of Severe Neurological Complications.

The concurrence of COVID-19 with Guillain-Barre syndrome (GBS) can increase the likelihood of neuromuscular respiratory failure, autonomic dysfunction, and other life-threatening symptoms. Currently, very little is known about the underlying mechanisms, clinical course, and prognostic implications of comorbid COVID-19 in patients with GBS. We reviewed COVID-19-associated GBS case reports published since the outbreak of the pandemic, with a database search up to August 2020, including a manual search of the reference lists for additional relevant cases.

Barriers to biomedical care for people with epilepsy in Uganda: A cross-sectional study.

Objective: Epilepsy, a neurological disorder with effective biomedical treatment, remains largely untreated in Uganda. Potential reasons for this treatment gap (TG) include limited access to trained providers and clinics, social stigmata of seizures, cultural beliefs, or lack of public understanding of epilepsy as a treatable condition. The current study aimed to formally evaluate barriers faced by people with epilepsy (PWE) in Uganda when seeking biomedical care.

Understanding the cultural context of epilepsy care in Uganda: Introduction to this special issue.

This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".

Stigma reduction interventions for epilepsy: A systematized literature review.

Objective: Epilepsy is a disease that is stigmatized globally. Several studies have introduced sensitization efforts to reduce stigma towards people with epilepsy (PWE) in various settings. Although sensitization efforts have shown some evidence of improved attitudes towards epilepsy, progress has been limited.

Leveraging the lessons learned from studies on the cultural context of epilepsy care in Uganda: Opportunities and future directions.

In this summary paper, we review the body of research contained in this special issue, The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda, and corollary recommendations for a way forward. We review key findings and conclusions for the studies, which tell a story of culture and care-seeking through discussions and data gleaned from a rich research landscape traversing community village dwellings, shared communal areas, churches, and urban hospitals. The voices and perspectives of over 16,000 study participants inclusive of people living with epilepsy, their neighbors and healthcare workers, traditional healers, and faith leaders are reported.

Hospital-based epilepsy care in Uganda: A prospective study of three major public referral hospitals.

Objective: This study sets out to describe the current demographics of people with epilepsy (PWE) attending hospital-based care in Uganda and the epilepsy treatment practices within three of the largest Ugandan public referral hospitals.

Methods: In a six-month prospective cohort study, 626 children and adults attending epilepsy clinics at Mulago National Referral Hospital, Butabika National Referral Mental Hospital and Mbarara Regional Referral Hospital were enrolled. Using a study questionnaire, data were collected at baseline and at 3 weeks, 3 months, and 6 months following enrollment.

Pluralistic and singular causal attributions for epilepsy in Uganda.

Objective: In Uganda, causal attributions for epilepsy reflect a variety of beliefs and impact care-seeking behavior, perpetuate stigma, and undermine the effectiveness of interventions to narrow the epilepsy treatment gap. The objective of this study was to characterize beliefs about seizure etiology to gain a better understanding of how epilepsy is conceptualized in the community in order to inform culturally appropriate educational policies and interventions.

Methods: In a community-based study, 15,383 participants were surveyed about beliefs related to 15 potential causes for epilepsy.

Sociocultural determinants and patterns of healthcare utilization for epilepsy care in Uganda.

Objective: Epilepsy is a global public health concern, with the majority of cases occurring in lower- and middle-income countries where the treatment gap remains formidable. In this study, we simultaneously explore how beliefs about epilepsy causation, perceived barriers to care, seizure disorder characteristics, and demographics influence the initial choice of healthcare for epilepsy and its impact on attaining biomedical care (BMC).

Methods: This study utilized the baseline sample (n = 626) from a prospective cohort study of people with epilepsy (PWE) attending three public hospitals in Uganda (Mulago National Referral Hospital, Butabika National Referral Mental Hospital, and Mbarara Regional Referral Hospital) for epilepsy care.

Healthcare provider perspectives regarding epilepsy care in Uganda.

Objective: Epilepsy is the most common chronic neurological disorder in the world and imposes a large economic burden on global healthcare systems, especially in low-income settings and rural areas as is found in sub-Saharan Africa (SSA). Despite the high epilepsy prevalence, there are no systematic descriptions of healthcare provider (HCP) perceptions and needs in managing people with epilepsy (PWE) in Uganda. Identifying these perceptions and needs is crucial for understanding community priorities, thereby enhancing the development of culturally sensitive communications, interventions, and research approaches.

Epilepsy beliefs and misconceptions among patient and community samples in Uganda.

Objective: The objective of the study was to characterize and compare the attitudes, beliefs, and perceptions about epilepsy across community and patient cohorts in Uganda.

Methods: This was a descriptive study utilizing two samples: a randomly selected, national survey community sample and a hospital-based patient sample of people with epilepsy (PWE) and their caregivers attending clinic settings in Kampala and Mbarara, Uganda for epilepsy care. Both samples were surveyed about their beliefs about epilepsy, its treatment, and people who have the illness.

Stakeholder views of the practical and cultural barriers to epilepsy care in Uganda.

Objective: Epilepsy is one of the most prevalent, treatable neurological diseases globally. In sub-Saharan Africa, people with epilepsy (PWE) frequently seek treatment from traditional or pastoral healers, who are more accessible than biomedical care providers. This often contributes to the substantial time delay in obtaining adequate biomedical care for these patients.

Validity of the Personal Impact of Epilepsy Scale (PIES) in patients with epilepsy in Uganda.

Purpose: We sought to address the construct validity and reliability of the Personal Impact of Epilepsy Scale (PIES), an epilepsy-specific quality-of-life measure, in patients with epilepsy in Uganda. We also sought to assess the applicability of the scale across three languages: English, Luganda, and Runyankole.

Methods: Patients with epilepsy (N = 626) were recruited at the time of care seeking from Mulago National Referral Hospital (MNRH), Butabika National Referral Mental Hospital (BNRMH), and Mbarara Regional Referral Hospital (MRRH), and were given the English, Runyankole, and Luganda versions of the PIES as a part of a larger interview.

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.

Intelligence is highly heritable and a major determinant of human health and well-being. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis.

A large food-borne outbreak of group A streptococcal pharyngitis in an industrial plant: potential for deliberate contamination.

Contamination of food with streptococci could present with unusual outbreaks that may be difficult to recognize in the early stages. This is demonstrated in a large food-borne outbreak of streptococcal pharyngitis that occurred in 2003 in a factory in Israel. The outbreak was reported to the public health services on July 2 and an epidemiologic investigation was initiated.