Endoplasmic reticular stress as an emerging therapeutic target for chronic pain: a narrative review.

Chronic pain is a severely debilitating condition with enormous socioeconomic costs. Current treatment regimens with nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or opioids have been largely unsatisfactory with uncertain benefits or severe long-term side effects. This is mainly because chronic pain has a multifactorial aetiology.

Early-adulthood spike in protein translation drives aging via juvenile hormone/germline signaling.

Protein translation (PT) declines with age in invertebrates, rodents, and humans. It has been assumed that elevated PT at young ages is beneficial to health and PT ends up dropping as a passive byproduct of aging. In Drosophila, we show that a transient elevation in PT during early-adulthood exerts long-lasting negative impacts on aging trajectories and proteostasis in later-life.

Protein translation paradox: Implications in translational regulation of aging.

Protein translation is an essential cellular process playing key roles in growth and development. Protein translation declines over the course of age in multiple animal species, including nematodes, fruit flies, mice, rats, and even humans. In all these species, protein translation transiently peaks in early adulthood with a subsequent drop over the course of age.

Genetic and pharmacologic proteasome augmentation ameliorates Alzheimer's-like pathology in mouse and fly APP overexpression models.

The proteasome has key roles in neuronal proteostasis, including the removal of misfolded and oxidized proteins, presynaptic protein turnover, and synaptic efficacy and plasticity. Proteasome dysfunction is a prominent feature of Alzheimer's disease (AD). We show that prevention of proteasome dysfunction by genetic manipulation delays mortality, cell death, and cognitive deficits in fly and cell culture AD models.

Gut- and oral-dysbiosis differentially impact spinal- and bulbar-onset ALS, predicting ALS severity and potentially determining the location of disease onset.

Background: Prior studies on the role of gut-microbiome in Amyotrophic Lateral Sclerosis (ALS) pathogenesis have yielded conflicting results. We hypothesized that gut- and oral-microbiome may differentially impact two clinically-distinct ALS subtypes (spinal-onset ALS (sALS) vs. bulbar-onset ALS (bALS), driving disagreement in the field.

Congenital Rubella Syndrome Surveillance in South Africa Using a Sentinel Site Approach: A Cross-sectional Study.

Background: Congenital rubella syndrome (CRS) includes disorders associated with intrauterine rubella infection. Incidence of CRS is higher in countries with no rubella-containing vaccines (RCV) in their immunization schedules. In the World Health Organization African region, RCVs are being introduced as part of the 2012-2020 global measles and rubella strategic plan.

HIV-1 disease progression in immune-competent HIV-1-infected and breastfeeding mothers participating in the ANRS 12174 clinical trial in Burkina Faso, South Africa, Uganda and Zambia: a cohort study.

Objective: We have assessed HIV-1 disease progression among HIV-1-positive mothers in relation to duration of any or exclusive breast feeding in the context of ANRS 12174 trial.

Methods: The analysis was completed on 203, 212, 272 and 529 HIV-1-positive and lactating mothers with CD4 count >350 cells/µL from Burkina Faso, South Africa, Uganda and Zambia, respectively. The trial compared lamivudine and lopinavir/ritonavir as a peri-exposure prophylaxis during a 50-week follow-up time.

Breastfeeding patterns and its determinants among mothers living with Human Immuno-deficiency Virus -1 in four African countries participating in the ANRS 12174 trial.

Background: HIV-1 transmission rates have been reduced over the last decade, an estimated 2 million new infections per year arise, including 220,000 paediatric cases. The main post-natal HIV exposure is through breastfeeding, where both its duration and modality (exclusive or not) are associated with postnatal transmission. The ANRS 12174 trial compared HIV-1 postnatal transmission of 2 prophylaxis drugs for infants during lactation (lamivudine and lopinavir-ritonavir).

Are Prophylactic and Therapeutic Target Concentrations Different?: the Case of Lopinavir-Ritonavir or Lamivudine Administered to Infants for Prevention of Mother-to-Child HIV-1 Transmission during Breastfeeding.

The ANRS 12174 trial assessed the efficacy and tolerance of lopinavir (LPV)-ritonavir (LPV/r) prophylaxis versus those of lamivudine (3TC) prophylaxis administered to breastfed infants whose HIV-infected mothers were not on antiretroviral therapy. In this substudy, we assessed LPV/r and 3TC pharmacokinetics to evaluate the percentage of infants with therapeutic plasma concentrations and to discuss these data in the context of a prophylactic treatment. Infants from the South African trial site underwent blood sampling for pharmacokinetic study at weeks 6, 26, and 38 of life.

Lamivudine Monotherapy: Experience of Medium-term Outcomes in HIV-infected Children Unable to Adhere to Triple Therapy.

Background: HIV-infected children in resource-poor settings who fail or default from first-line antiretroviral therapy have limited alternative options. By preferentially selecting the M184V mutation, lamivudine monotherapy (LM) is occasionally used while awaiting patient readiness for second- or third-line therapy, but this strategy has not been widely studied.

Methods: A retrospective review of all eligible LM events (≥3 months) from a cohort of two linked health facilities in the Eastern Cape Province, South Africa was undertaken.

Lamivudine monotherapy as a safe option for HIV-infected paediatric clients with adherence challenges: new evidence from a large South African cohort.

Introduction: HIV-infected children in resource-poor settings comprise a unique population who require antiretroviral therapy (ART) in careful consideration of social and structural barriers to compliance. Given these aggregate challenges and emerging research into "holding" treatment options, we investigated the efficacy of lamivudine monotherapy (LM) as an alternative to more complex second and third line therapies.

Methods: A retrospective review of all eligible LM events (=6 months) from a cohort of two linked health facilities in the Eastern Cape Province, South Africa was undertaken.

Group work with female survivors of childhood sexual abuse: evidence of poorer outcomes among those with eating disorders.

Objective: This study explored levels of depression and self-esteem after childhood sexual abuse (CSA) group treatment for survivors with and without histories of eating disorders (ED).

Methods: Fifty adult female survivors completed a 15-week CSA group treatment program and were assessed at intake, pre-group treatment, discharge, and six months follow-up using the Beck Depression Inventory, the Generalized Contentment Scale and the Index of Self-Esteem. They were also asked to report on their CSA histories and comorbid psychiatric issues including histories of ED.

Insecure attachment as a predictor of outcome following inpatient trauma treatment for women survivors of childhood abuse.

The role of insecure attachment as a predictor of outcome was investigated in 134 women who reported histories of child abuse and completed an inpatient program for treatment of traumatic stress. Multiple linear regressions were used to predict the change scores on four outcome measures at discharge and 6-month follow-up. Higher levels of feared loss of the attachment figure independent of demographics, symptomatic severity, and trauma exposure consistently predicted poorer outcome at both post-tests.

What works for survivors of childhood abuse: learning from participants in an inpatient treatment program.

Thirty adults were interviewed about their experiences in a 6-week program for recovery from posttraumatic stress. The most valued aspects were their relationships with staff and the staff's expertise in treating the long-term effects of abuse. They valued the structured group treatment that allowed them to process emotions with the goal of healing.

Therapeutic boundary issues in working with childhood sexual-abuse survivors.

The article describes a study of therapists involved in treating survivors of childhood sexual abuse. The authors focus on what induces participants to change their usual therapeutic boundaries. Through qualitative research utilizing extensive interviews, written questionnaires, and a focus-group discussion, the authors gathered information from therapists related to situations that influence them to change their own boundaries.