Long-term outcomes of subthalamic nucleus deep brain stimulation for Parkinson's disease in Singapore.

Introduction: Subthalamic nucleus deep brain stimulation (STN-DBS) is a proven treatment modality for Parkinson's disease (PD), reducing dyskinesia and time spent in the "OFF" state. This study evaluates the long-term outcomes of STN-DBS in PD patients up to 10 years post-surgery in Singapore.

Method: We conducted a retrospective review of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores, activities of daily living (ADLs), disease milestones, dopaminergic drug prescriptions, and adverse events in patients before and after STN-DBS surgery.

Outcomes after deep brain stimulation for elderly versus non-elderly patients with Parkinson's disease.

Introduction: The decision to offer deep brain stimulation (DBS) to elderly patients with Parkinson's disease (PD) presents challenges due to higher perceived risks and uncertain long-term benefits. Here, we aimed to compare the outcomes after DBS for elderly versus non-elderly patients with PD.

Methods: We analyzed data from our institutional cohort and retrieved publicly available data through a systematic review.

Inferring cancer disease response from radiology reports using large language models with data augmentation and prompting.

Objective: To assess large language models on their ability to accurately infer cancer disease response from free-text radiology reports.

Materials And Methods: We assembled 10 602 computed tomography reports from cancer patients seen at a single institution. All reports were classified into: no evidence of disease, partial response, stable disease, or progressive disease.

Cannabidiol modulates expression of type I IFN response genes and HIV infection in macrophages.

Cannabis () is a widely used drug in the United States and the frequency of cannabis use is particularly high among people living with HIV (PLWH). One key component of cannabis, the non-psychotropic (-)-cannabidiol (CBD) exerts a wide variety of biological actions, including anticonvulsive, analgesic, and anti-inflammatory effects. However, the exact mechanism of action through which CBD affects the immune cell signaling remains poorly understood.

Comparison of continuous preperitoneal infiltration versus patient controlled analgesia for pain control in elective colorectal surgery.

Background: Post-operative analgesia is crucial in enhanced recovery after surgery and to minimize post-operative complications. There remains data paucity on the efficacy of preperitoneal analgesia (PPA) compared to patient-controlled analgesia (PCA). This study aims to examine the efficacy of preperitoneal infusion as analgesia following elective colorectal surgery.

No infectious SARS-CoV-2 in breast milk from a cohort of 110 lactating women.

Background: Genomic RNA of severe acute respiratory syndrome-associated coronavirus type 2 (SARS-CoV-2) has been detected in the breast milk of lactating women, but its pathological significance has remained uncertain due to the small size of prior studies.

Methods: Breast milk from 110 lactating women was analyzed by reverse transcription-polymerase chain reaction (285 samples) and viral culture (160 samples). Those containing SARS-CoV-2 viral RNA (vRNA) were examined for the presence of subgenomic RNA (sgRNA), a putative marker of infectivity.

Longitudinal Healthcare Utilization and Costs in Parkinson's Disease: Pre-Diagnosis to 9 Years After.

Background: There is currently insufficient long-term data on costs of treatment in patients with Parkinson's disease (PD), which is chronic and progressive, and associated with substantial healthcare costs. Identifying patterns in healthcare utilization and cost may illuminate further discussion on early intervention.

Objective: To characterize long-term healthcare utilization and costs of PD in newly diagnosed patients managed by movement disorder specialists.

No Evidence of Infectious SARS-CoV-2 in Human Milk: Analysis of a Cohort of 110 Lactating Women.

Background: SARS-CoV-2 infections of infants and toddlers are usually mild but can result in life-threatening disease. SARS-CoV-2 RNA been detected in the breast milk of lactating women, but the potential role of breastfeeding in transmission to infants has remained uncertain.

Methods: Breast milk specimens were examined for the presence of the virus by RT-PCR and/or culture.

Evolution of Initial Pharmacologic Treatment of Newly Diagnosed Parkinson's Disease Patients over a Decade in Singapore.

Objective: The aim of this study is to compare Parkinson's disease (PD) treatment practices by movement disorder (MD) specialists across a decade, and to determine the factors that influence drug choice for the motor symptoms of PD in newly diagnosed drug-naïve patients.

Methods: This prospective temporal analysis included patients seen at the National Neuroscience Institute in Singapore and diagnosed with PD by MD specialists in the years 2007 and 2017. Primary outcomes were use of specific PD drugs and changes in drug-prescribing patterns.

Suboptimal stimulation by weak agonist epitope variants does not drive dysfunction of HIV-1-specific cytotoxic T lymphocyte clones.

Objective: To assess whether weakly recognized epitope variants induce anergy in HIV-1-specific CD8 T lymphocyte (CTL) clones as a mechanism of dysfunction.

Design: HIV-1-specific CTL clones were exposed to suboptimally recognized epitope variants, and screened for anergy and other T-cell dysfunction markers, and subsequent capability to kill target cells bearing index epitope.

Methods: In addition to the optimally recognized index epitope, two suboptimally recognized epitope variants were selected based on titration curves for killing of peptide-labeled target cells by three HIV-1-specific CTL clones targeting the epitopes SLYNTVATL (Gag 77-85, A02-restricted), RPAEPVPLQL (Rev 66-75, B07-restricted), and KRWIIMGLNK (Gag 263-272, B27-restricted).

CD8 Cytotoxic T Lymphocyte Responses and Viral Epitope Escape in Acute HIV-1 Infection.

Epitope escape from HIV-1-targeted CD8 cytotoxic T lymphocyte (CTL) responses occurs rapidly after acute infection and contributes to the eventual failure of effective immune control of HIV-1 infection. Because the early CTL response is key in determining HIV-1 disease outcome, studying the process of epitope escape is crucial for understanding what leads to failure of immune control in acute HIV-1 infection and will provide important implications for HIV-1 vaccine design. HIV-1-specific CD8 T lymphocyte responses against viral epitopes were mapped in six acutely infected individuals, and the magnitudes of these responses were measured longitudinally during acute infection.

Cross-Reactivity against Multiple HIV-1 Epitopes Is Characteristic of HIV-1-Specific Cytotoxic T Lymphocyte Clones.

Although a high level of promiscuity for heterologous epitopes is believed to exist for cellular immunity, limited data explore this issue for human immunodeficiency virus type 1 (HIV-1)-specific CD8 T lymphocyte (CTL) responses. Here, we found an unexpected degree of heterologous cross-reactivity against HIV-1 epitopes, in addition to the targeted index epitope. Most CTL clones screened cross-reacted against other known HIV-1 epitopes of the same major histocompatibility complex type I (MHC-I) restriction, up to 40% of tested nonindex epitopes in some cases.

Highly Attenuated Infection With a Vpr-Deleted Molecular Clone of Human Immunodeficiency Virus-1.

A 48-year-old woman was infected with a vpr-defective human immunodeficiency virus (HIV)-1 molecular clone. Seroconversion was markedly delayed, and without treatment she had durably suppressed viremia and normal T-cell levels. Neutralizing antibody and CD8+ T-cell immune responses against HIV-1 were unremarkable.

Acupuncture in the treatment of fatigue in Parkinson's disease: A pilot, randomized, controlled, study.

Introduction: Fatigue is a common and disabling problem in patients with Parkinson's disease (PD), and there is currently no satisfactory treatment. As acupuncture has been reported to be effective in fatigue related to other conditions, we sought to evaluate its efficacy in PD.

Methods: This was a single center, randomized, sham-controlled study.

Solution Structures of Engineered Vault Particles.

Prior crystal structures of the vault have provided clues of its structural variability but are non-conclusive due to crystal packing. Here, we obtained vaults by engineering at the N terminus of rat major vault protein (MVP) an HIV-1 Gag protein segment and determined their near-atomic resolution (∼4.8 Å) structures in a solution/non-crystalline environment.

HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes.

Certain Major Histocompatibility-I (MHC-I) types are associated with superior immune containment of HIV-1 infection by CD8+ cytotoxic T lymphocytes (CTLs), but the mechanisms mediating this containment are difficult to elucidate in vivo. Here we provide controlled assessments of fitness landscapes and CTL-imposed constraints for immunodominant epitopes presented by two protective (B*57 and B*27) and one non-protective (A*02) MHC-I types. Libraries of HIV-1 with saturation mutagenesis of CTL epitopes are propagated with and without CTL selective pressure to define the fitness landscapes for epitope mutation and escape from CTLs via deep sequencing.

HIV-1 Epitope Variability Is Associated with T Cell Receptor Repertoire Instability and Breadth.

Mutational escape of HIV-1 from HIV-1-specific CD8 T lymphocytes (CTLs) is a major barrier for effective immune control. Each epitope typically is targeted by multiple clones with distinct T cell receptors (TCRs). While the clonal repertoire may be important for containing epitope variation, determinants of its composition are poorly understood.

Structures and stabilization of kinetoplastid-specific split rRNAs revealed by comparing leishmanial and human ribosomes.

The recent success in ribosome structure determination by cryoEM has opened the door to defining structural differences between ribosomes of pathogenic organisms and humans and to understand ribosome-targeting antibiotics. Here, by direct electron-counting cryoEM, we have determined the structures of the Leishmania donovani and human ribosomes at 2.9 Å and 3.

HIV-1-Specific Chimeric Antigen Receptors Based on Broadly Neutralizing Antibodies.

Unlabelled: Although the use of chimeric antigen receptors (CARs) based on single-chain antibodies for gene immunotherapy of cancers is increasing due to promising recent results, the earliest CAR therapeutic trials were done for HIV-1 infection in the late 1990s. This approach utilized a CAR based on human CD4 as a binding domain and was abandoned for a lack of efficacy. The growing number of HIV-1 broadly neutralizing antibodies (BNAbs) offers the opportunity to generate novel CARs that may be more active and revisit this modality for HIV-1 immunotherapy.

Treatment Preferences at the End-of-Life in Parkinson's Disease Patients.

Background: Few studies have been performed on palliative care in Parkinson's disease (PD). This study was undertaken to understand treatment preferences of PD patients toward end-of-life care.

Methods: A questionnaire modified from the Willingness to Accept Life-Sustaining Treatment instrument was administered to participants.

Clonal CD8+ T Cell Persistence and Variable Gene Usage Bias in a Human Transplanted Hand.

Immune prophylaxis and treatment of transplanted tissue rejection act indiscriminately, risking serious infections and malignancies. Although animal data suggest that cellular immune responses causing rejection may be rather narrow and predictable based on genetic background, there are only limited data regarding the clonal breadth of anti-donor responses in humans after allogeneic organ transplantation. We evaluated the graft-infiltrating CD8+ T lymphocytes in skin punch biopsies of a transplanted hand over 178 days.

Ectopic expression of anti-HIV-1 shRNAs protects CD8(+) T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation.

Chimeric antigen receptors (CARs) are artificially engineered receptors that confer a desired specificity to immune effector T cells. As an HIV-1-specific CAR, CD4ζ CAR has been extensively tested in vitro as well as in clinical trials. T cells modified with this CAR mediated highly potent anti-HIV-1 activities in vitro and were well-tolerated in vivo, but exerted limited effects on viral load and reservoir size due to poor survival and/or functionality of the transduced cells in patients.