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Background: Resting tremor is a prominent cardinal motor symptom of Parkinson’s disease (PD). In some cases, the tremor may be refractory to dopaminergic and anticholinergic treatment. Multiple studies were previously done to evaluate the effectiveness of Botulinum Neurotoxin A (BoNT/A) with essential tremors and dystonia, but data regarding its use on tremors of PD is still lacking. Objective: This meta-analytic study aims to determine the effectiveness of BoNT/A in treating tremors of patients with PD. Data Sources: Researches were searched at PubMed, ScienceDirect and EBSCO Host. Review Methods: Articles on the effect of BoNT/A on PD hand tremors were searched. Studies and data pertaining to non-PD tremors like essential tremors excluded in the analysis due to difference in pathophysiology. Standardized mean difference was used as the effect measure and was computed with Review Manager version 5.4 software. Results: Three open label studies were used for final analysis in this study. Studies included are those pertaining to tremors due to PD. Pooled estimates showed a significant change in decreasing tremor score after BoNT/A injection. Conclusion: Botulinum Toxin A injections can be used to manage PD tremors effectively. Keywords: Botulinum neurotoxin A, Botox A, Btx, tremors, Parkinson’s disease

Introduction: The ‘first generation’ physician gathers a lot of strength to venture into a world unknown to him. Unlike a physician born to a family of physicians who has a family to guide him, the ‘first generation’ physician only has himself to survive this endeavor. Through the life worlds of a select group of ‘first generation’ physician-in-training, this study seeks to answer the following central question: How do ‘first generation’ Filipino physicians collectively characterize their liminal spaces in transition from medical school to clinical practice? Methodology: Anchored on the Theory of the Rites of Passage, this phenomenological inquiry, intends to surface the lebenswelt or essence of the experience of being the only physician in the family. Respondents comprised a purposive sample of physicians-in-training (residents and fellows), who are the only physicians in the family. Data were gathered using semi-structured interviews. Triangulation and member checking procedures were done to ensure the data reliability. Data were then subjected to cool (categorization) and warm analysis (thematization) using the Colaizzi's method. Findings and Discussion: With all the transcribed experiences summarized and those with the same meaning analyzed, the following categories and themes were generated: The Intending Facet / Purpose: From Uncertainty towards Redefinition; The Thinking Facet / Process: From Perplexity towards Self-efficacy; The Relating Facet / People: From Isolation towards Integration; and The Transforming Facet / Power: From Vulnerability towards Empowerment. It was shown that a ‘first generation’ physician in this liminal space undergoes challenges and struggles during his training in medicine. This served as his Rite of Passage to transition him to someone dreaming only to become a physician, to become redefined with conviction, supported and integrated into the health system, empowered and transformed to the physician he is meant to be. Recommendations: Physicians undergo a lot of challenges and mental stress and it means a lot for trainers to enter into the trainees’ life-world, especially that of a ‘first generation’ physician, so that they can build socio-emotional learning and mentoring programs and counselling services that address different facets of liminal space that the trainees go through.

Background Cryptococcal meningitis (CM) and disseminated histoplasmosis (DH) are common in people with human immunodeficiency virus (PWH) and diagnosed by detecting cryptococcal antigen (CrAg) and Histoplasma antigen (HistoAg), respectively. In Ghana, CM and DH are rarely suspected by clinicians due to limited epidemiological data. Methods This study was conducted among PWH in Ghana who are unwell. Sociodemographic and clinical data were collected by questionnaire. Serum and/or urine were screened for CrAg and HistoAg, using IMMY CrAg lateral flow assay (LFA) and IMMY Histoplasma enzyme immunoassay (EIA) kits, respectively, regardless of symptoms. Samples run with IMMY Histoplasma EIA were simultaneously run with Optimum Imaging Diagnostics (OIDx) Histoplasma LFA. Laboratory investigations were conducted by the research team, and diagnosis incorporating clinical assessment, screening, and confirmatory testing results and treatment decisions were made by the clinical team. Treatment and outcome information on CM and DH patients were evaluated. Results Overall, 150 participants were recruited. There were 73% (n = 109) females, and the age range was 18–62 years. The prevalence rates of CrAg and HistoAg were 2.7% (4 of 150) and 4.7% (5 of 107), respectively. The OIDx Histoplasma LFA showed a high concordance (98.4%) with the IMMY Histoplasma EIA. All antigen-positive cases by standard tests were diagnosed with CM and DH. Antifungal treatment was given in 5 patients and follow-up revealed 2 deaths and 3 recoveries. Conclusions Histoplasmosis among PWH may be more common than previously anticipated and may be more frequent than cryptococcosis in Ghana. The performance of the OIDx Histoplasma LFA should be further explored.

The Golgi is a major site of glycan processing mediated by a large number of Golgi-resident glycosylation enzymes. These enzymes are largely type II transmembrane domain (TMD) proteins consisting of a short N-terminal cytosolic tail, a short TMD and a lumenal ‘stem’ region which separates the catalytic domain and the lipid bilayer. The cytosolic tail, TMD, and stem together make the CTS domain which is responsible for the Golgi-targeting of these enzymes via multiple COPI-dependent mechanisms. What is not clear is the relative contribution of each mechanism to Golgi retention or how they work to fine tune the sub-Golgi localisation of these enzymes. To explore these nuances of intra-Golgi traffic, a MitoID proteomic screen was applied to the intra-Golgi golgin tethers GMAP-210 and golgin-84 to identify novel intra-Golgi vesicle-resident factors. The screen identified the Rab2 effector of unknown function FAM114A2. FAM114A2 and paralogous protein FAM114A1 were shown to specifically associate with early-Golgi membranes. A predicted ALPS motif was necessary for membrane association, presumably through non-specifically absorbing onto highly-curved membranes. Other regions of the proteins were required to mediate a specific association with membranes of the early-Golgi. GST affinity chromatography and mass spectrometry revealed that FAM114A1 pulled down Rab2A and Rab2B while FAM114A2 pulled down several COPI cargo proteins including many glycosylation enzymes. FAM114A2 interacted directly with the cytoplasmic tails of cargo which had a membrane-proximal polybasic motif. Similar binding studies revealed that the COPI adaptors GOLPH3+3L pulled down the COPI coat and over a hundred novel clients. GOLPH3+3L were shown to interact promiscuously with the cytoplasmic tails of clients with a total predicted charge of ≥4+. An in vivo Golgi retention assay revealed that tails which satisfy the GOLPH3+3L charge threshold are sufficient to impart Golgi-retention in a GOLPH3+3L-dependent manner. The deletion of FAM114A genes had no impact on retention in this assay. The assay also showed that the TMD of ST6GAL1 was sufficient to impart Golgi retention in a GOLPH3+3L-independent manner. The deletion of GOLPH3+3L, but not FAM114A genes, triggered the lysosomal degradation of COPI cargo and caused a global defect in glycosylation in U2OS cells. In contrast, deletion of the D. melanogaster FAM114A ortholog CG9590 caused a defect in mucin-type glycosylation in adult flies. CG9590 interacted directly with the COPI coat and pulled-down a host of COPI cargo proteins including mucin-type glycosylation enzymes. It is likely that FAM114A is an evolutionary-conserved COPI adaptor which acts to recycle a specific subset of COPI cargo from the early-Golgi. In contrast, GOLPH3 proteins are promiscuous COPI adaptors which function as master gatekeepers at the late-Golgi to recycle and retain a broad array of Golgi-residents.