Mitophagy is an important type of selective autophagy for specific elimination of damaged mitochondria. PTEN-induced putative kinase protein 1 (PINK1)-catalyzed phosphorylation of ubiquitin (Ub) plays a critical role in the onset of PINK1-Parkin-mediated mitophagy. Phosphatase and tensin homolog (PTEN)-long (PTEN-L) is a newly identified isoform of PTEN, with addition of 173 amino acids to its N-terminus. Here we report that PTEN-L is a novel negative regulator of mitophagy via its protein phosphatase activity against phosphorylated ubiquitin. We found that PTEN-L localizes at the outer mitochondrial membrane (OMM) and overexpression of PTEN-L inhibits, whereas deletion of PTEN-L promotes, mitophagy induced by various mitochondria-damaging agents. Mechanistically, PTEN-L is capable of effectively preventing Parkin mitochondrial translocation, reducing Parkin phosphorylation, maintaining its closed inactive conformation, and inhibiting its E3 ligase activity. More importantly, PTEN-L reduces the level of phosphorylated ubiquitin (pSer65-Ub) in vivo, and in vitro phosphatase assay confirms that PTEN-L dephosphorylates pSer65-Ub via its protein phosphatase activity, independently of its lipid phosphatase function. Taken together, our findings demonstrate a novel function of PTEN-L as a protein phosphatase for ubiquitin, which counteracts PINK1-mediated ubiquitin phosphorylation leading to blockage of the feedforward mechanisms in mitophagy induction and eventual suppression of mitophagy. Thus, understanding this novel function of PTEN-L provides a key missing piece in the molecular puzzle controlling mitophagy, a critical process in many important human diseases including neurodegenerative disorders such as Parkinson's disease.

Introduction: Vaccination remains a key strategy to living endemically with COVID-19. The Pfizer-BioNTech COVID-19 vaccine was first granted interim authorisation for use in Singapore in December 2020. With overseas studies published about the safety and side effect profiles of mRNA COVID-19 vaccines focusing mainly on non-Asian populations, we described the side effects of Pfizer-BioNTech COVID-19 vaccination experienced by the healthcare workers (HCWs) in a tertiary hospital in Singapore. Methods: Data were obtained from the Occupational Health Clinic (OHC) at the National University Hospital in Singapore, which monitored staff for any adverse effects within 30 minutes postvaccination on-site and any adverse effects after that. A cross-sectional study among the vaccinated HCWs was conducted using an online survey, which established basic demographics, histories of allergies or atopic disorders, and adverse events encountered after dose 1 and dose 2 of vaccination. Results: No anaphylaxis was reported. Most common symptom was giddiness (32.7%) experienced by HCWs within 30 minutes. Adverse events attended post-vaccination by OHC were generally mild and self-limiting. From the survey, odds of experiencing an adverse event after dose 2 was significantly higher than after the first dose, especially for fever/chills (odds ratio [OR] 22.5). Fever/chills, injection site reactions, headache, aches and pains, and feeling unwell were significantly more common in HCWs below 60 years compared to those ≥60 years. An allergy to food (adjusted OR 2.7) and a history of eczema/sensitive skin (adjusted OR 2.6) were associated with a skin reaction not at injection site. Conclusion: The side effects experienced after Pfizer-BioNTech COVID-19 vaccines are generally self-limiting and mild, with no anaphylaxis reported. Keywords: COVID-19, infectious diseases, occupational medicine, side effects, vaccination

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BackgroundEarly diagnosis of human immunodeficiency virus (HIV) allows for appropriately timed interventions with improved outcomes, but HIV screening among asymptomatic persons and the general population in Singapore remains low. In 2008, Singapore’s Ministry of Health implemented HIV voluntary opt-out screening (VOS) for hospitalised adults. We evaluated the outcome of VOS and surveyed reasons for its low uptake in our institution.MethodsWe assessed the outcomes of the VOS programme from January 2010 to December 2013 at National University Hospital, a 1081-bed tertiary hospital in Singapore. We also examined reasons for opting-in and opting-out using an interviewer–administered structured questionnaire in a representative sample in January 2013.Results107,523 patients fulfilled VOS criteria and were offered HIV screening, of which 5215 (4.9%) agreed to testing. 4850 (93.1%) of those who opted-in had an HIV test done. Three (0.06%) tested positive for HIV. 238 patients (14.2%) were surveyed regarding reasons for opting-in or out of VOS. 21 (8.8%) had opted-in. Patients who opted-in were likely to be younger, more educated and reported having more regular sexual partners. Type of housing, number of casual sexual partners, sexual orientation, intravenous drug use, condom use and previous sexually transmitted infection were not associated with deciding to opt-in/out. Patients’ most common reasons for opting-out were: belief that they were at low risk (50.2%), belief that they were too old (26.8%), cost (6.9%) and aversion to venepuncture (6.5%). The most common reason for opting-in was desire to know their HIV status (47.6%).ConclusionThe success of an HIV-VOS program is largely determined by test uptake. Our study showed that the majority of eligible VOS patients opted-out of HIV screening. Given the considerable cost and low yield of this programme, more needs to be done to better equip patients in self-risk assessment and opting in to testing.

A "stone in the pond" strategy is a practical approach to investigating large-scale nosocomial tuberculosis (TB) exposures. Here, we describe such a risk-stratified approach to contact tracing after a TB exposure that occurred over 5 months in a pediatric inpatient ward in a country with a moderate TB burden. Infect Control Hosp Epidemiol 2017;38:1509-1511.