Treponema pallidum Periplasmic and Membrane Proteins Are Recognized by Circulating and Skin CD4+ T Cells.

BACKGROUND: Histologic and serologic studies suggest the induction of local and systemic Treponema pallidum-specific CD4+ T-cell responses to T. pallidum infection. We hypothesized that T. pallidum-specific CD4+ T cells are detectable in blood and in the skin rash of secondary syphilis and persist in both compartments after treatment. METHODS: Peripheral blood mononuclear cells collected from 67 participants were screened by interferon-γ (IFN-γ) ELISPOT response to T. pallidum sonicate. T. pallidum-reactive T-cell lines from blood and skin were probed for responses to 89 recombinant T. pallidum antigens. Peptide epitopes and HLA class II restriction were defined for selected antigens. RESULTS: We detected CD4+ T-cell responses to T. pallidum sonicate ex vivo. Using T. pallidum-reactive T-cell lines we observed recognition of 14 discrete proteins, 13 of which localize to bacterial membranes or the periplasmic space. After therapy, T. pallidum-specific T cells persisted for at least 6 months in skin and 10 years in blood. CONCLUSIONS: T. pallidum infection elicits an antigen-specific CD4+ T-cell response in blood and skin. T. pallidum-specific CD4+ T cells persist as memory in both compartments long after curative therapy. The T. pallidum antigenic targets we identified may be high-priority vaccine candidates.

Treponema pallidum periplasmic and membrane proteins are recognized by circulating and skin CD4+ T cells.

Background: Histologic and serologic studies suggest the induction of local and systemic Treponema pallidum ( Tp )-specific CD4+ T cell responses to Tp infection. We hypothesized that Tp -specific CD4+ T cells are detectable in blood and in the skin rash of secondary syphilis and persist in both compartments after treatment. Methods: PBMC collected from 67 participants were screened by IFNγ ELISPOT response to Tp sonicate. Tp -reactive T cell lines from blood and skin were probed for responses to 88 recombinant Tp antigens. Peptide epitopes and HLA class II restriction were defined for selected antigens. Results: We detected CD4+ T cell responses to Tp sonicate ex vivo. Using Tp -reactive T cell lines we observed recognition of 14 discrete proteins, 13 of which localize to bacterial membranes or the periplasmic space. After therapy, Tp -specific T cells persisted for at least 6 months in skin and 10 years in blood. Conclusions: Tp infection elicits an antigen-specific CD4+ T cell response in blood and skin. Tp -specific CD4+ T cells persist as memory in both compartments long after curative therapy. The Tp antigenic targets we identified may be high priority vaccine candidates.

Case report: Left gaze and facial nerve palsies after ventral intermediate thalamic nucleus deep brain stimulation implantation.

Deep brain stimulation (DBS) to the ventral intermediate nucleus (VIM) of the thalamus has become a common procedure for some refractory, medication-resistant movement disorders like essential tremors. The most common adverse effects from this surgery include dysarthria and gait disturbances. This case report details a left gaze and ipsilateral facial nerve palsy following overshot cannula insertion into the pons during a VIM DBS procedure. Initial patient presentation after surgery revealed significant impairment of horizontal gaze to the left. This improved during follow-up visits and after the recession of the bilateral medial recti. When considering complications of the VIM DBS procedure, surgeons should be aware of the risks of cannula overshot given the anatomic proximity between the thalamus and brainstem. Furthermore, patients should be aware of this risk when making their surgical decision. All patients who undergo VIM DBS should be assessed for cranial nerve deficits after placement.

Transient Receptor Potential (TRP) Channels in Pain, Neuropsychiatric Disorders, and Epilepsy.

Pharmacomodulation of membrane channels is an essential topic in the study of physiological conditions and disease status. Transient receptor potential (TRP) channels are one such family of nonselective cation channels that have an important influence. In mammals, TRP channels consist of seven subfamilies with a total of twenty-eight members. Evidence shows that TRP channels mediate cation transduction in neuronal signaling, but the full implication and potential therapeutic applications of this are not entirely clear. In this review, we aim to highlight several TRP channels which have been shown to mediate pain sensation, neuropsychiatric disorders, and epilepsy. Recent findings suggest that TRPM (melastatin), TRPV (vanilloid), and TRPC (canonical) are of particular relevance to these phenomena. The research reviewed in this paper validates these TRP channels as potential targets of future clinical treatment and offers patients hope for more effective care.

College students' virtual and in-person drinking contexts during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has resulted in pronounced changes for college students, including shifts in living situations and engagement in virtual environments. Although college drinking decreased at the onset of the pandemic, a nuanced understanding of pandemic-related changes in drinking contexts and the risks conferred by each context on alcohol use and related consequences have yet to be assessed. METHODS: Secondary data analyses were conducted on screening data from a large parent clinical trial assessing a college student drinking intervention (N = 1669). Participants across six cohorts (from Spring 2020 to Summer 2021) reported on the frequency of drinking in each context (i.e., outside the home, home alone, home with others in-person, and home with others virtually), typical amount of drinking, and seven alcohol-related consequence subscales. RESULTS: Descriptive statistics and negative binomial regressions indicated that the proportion and frequency of drinking at home virtually with others decreased, while drinking outside the home increased from Spring 2020 to Summer 2021. Limited differences were observed in the proportion or frequency of individuals drinking at home alone or at home with others in-person. Negative binomial and logistic regressions indicated that the frequency of drinking outside the home was most consistently associated with more alcohol-related consequences (i.e., six of the seven subscales). However, drinking at home was not without risks; drinking home alone was associated with abuse/dependence, personal, social, hangover, and social media consequences; drinking home with others virtually was associated with abuse/dependence and social consequences; drinking home with others in-person was associated with drunk texting/dialing. CONCLUSION: The proportion and frequency of drinking in certain contexts changed during the COVID-19 pandemic, although drinking outside the home represented the highest risk drinking context across the pandemic. Future prevention and intervention efforts may benefit from considering approaches specific to different drinking contexts.

Amylin and Secretases in the Pathology and Treatment of Alzheimer's Disease.

Alzheimer's disease remains a prevailing neurodegenerative condition which has an array physical, emotional, and financial consequences to patients and society. In the past decade, there has been a greater degree of investigation on therapeutic small peptides. This group of biomolecules have a profile of fundamentally sound characteristics which make them an intriguing area for drug development. Among these biomolecules, there are four modulatory mechanisms of interest in this review: alpha-, beta-, gamma-secretases, and amylin. These protease-based biomolecules all have a contributory role in the amyloid cascade hypothesis. Moreover, the involvement of various biochemical pathways intertwines these peptides to have shared regulators (i.e., retinoids). Further clinical and translational investigation must occur to gain a greater understanding of its potential application in patient care. The aim of this narrative review is to evaluate the contemporary literature on these protease biomolecule modulators and determine its utility in the treatment of Alzheimer's disease.

Acid-Sensing Ion Channels in Glial Cells.

Acid-sensing ion channels (ASICs) are proton-gated cation channels and key mediators of responses to neuronal injury. ASICs exhibit unique patterns of distribution in the brain, with high expression in neurons and low expression in glial cells. While there has been a lot of focus on ASIC in neurons, less is known about the roles of ASICs in glial cells. ASIC1a is expressed in astrocytes and might contribute to synaptic transmission and long-term potentiation. In oligodendrocytes, constitutive activation of ASIC1a participates in demyelinating diseases. ASIC1a, ASIC2a, and ASIC3, found in microglial cells, could mediate the inflammatory response. Under pathological conditions, ASIC dysregulation in glial cells can contribute to disease states. For example, activation of astrocytic ASIC1a may worsen neurodegeneration and glioma staging, activation of microglial ASIC1a and ASIC2a may perpetuate ischemia and inflammation, while oligodendrocytic ASIC1a might be involved in multiple sclerosis. This review concentrates on the unique ASIC components in each of the glial cells and integrates these glial-specific ASICs with their physiological and pathological conditions. Such knowledge provides promising evidence for targeting of ASICs in individual glial cells as a therapeutic strategy for a diverse range of conditions.

Recovering from substance use disorders during the early months of the COVID-19 pandemic: A mixed-methods longitudinal study of women in Kansas City.

AIMS: During the early months of the U.S. COVID-19 outbreak, women suffered disproportionate burdens of pandemic-related psychological and economic distress. We aimed to describe the experiences of women in substance use disorder (SUD) recovery programs by (1) exploring the pandemic's impact on their lives, sobriety, and recovery capital and (2) tracking COVID-19 perceptions and preventative behaviors. METHODS: We conducted monthly semistructured interviews with women in residential and outpatient SUD recovery programs in Kansas City in April, May, and June 2020. Participants described the pandemic's impact on their life and sobriety and completed survey items on factors related to COVID-19 preventative behaviors. We interpreted qualitative themes longitudinally alongside quantitative data. RESULTS: In 64 interviews, participants (n = 24) described reduced access to recovery capital, or resources that support sobriety, such as social relationships, housing, employment, and health care. Most experienced negative impacts on their lives and feelings of stability in March and April but maintained sobriety. Four women described relapse, all attributed to pandemic stressors. Participants described relief related to societal re-opening in May and June, and increased engagement with their communities, despite rising infection rates. CONCLUSIONS: For women recovering from SUDs during COVID-19, securing recovery capital often meant assuming greater COVID-19 risk. As substance use appeared to have increased during the pandemic and COVID-19 transmission continues, public health planning must prioritize adequate and safe access to recovery capital and timely distribution of vaccines to people struggling with SUDs.