Salt-losing nephropathy associated with severe hypothyroidism.

Here, we present a case of an older man presenting with worsening confusion. Laboratory tests showed serum sodium of 120 mmol/L with severe hypothyroidism and renal salt wasting that improved with treatment of hypothyroidism, normalising the serum sodium.

GTP Signaling Links Metabolism, DNA Repair, and Responses to Genotoxic Stress.

How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links metabolism to DNA repair and has significant therapeutic implications. GTP, but not other nucleotides, regulates the activity of Rac1, a guanine nucleotide-binding protein, which promotes the dephosphorylation of serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5). Dephosphorylated Abi-1, a protein previously not known to activate DNA repair, promotes nonhomologous end joining. In patients and mouse models of glioblastoma, Rac1 and dephosphorylated Abi-1 mediate DNA repair and resistance to standard-of-care genotoxic treatments. The GTP-Rac1-PP5-Abi-1 signaling axis is not limited to brain cancer, as GTP supplementation promotes DNA repair and Abi-1-S323 dephosphorylation in nonmalignant cells and protects mouse tissues from genotoxic insult. This unexpected ability of GTP to regulate DNA repair independently of deoxynucleotide pools has important implications for normal physiology and cancer treatment. SIGNIFICANCE: A newly described GTP-dependent signaling axis is an unexpected link between nucleotide metabolism and DNA repair. Disrupting this pathway can overcome cancer resistance to genotoxic therapy while augmenting it can mitigate genotoxic injury of normal tissues. This article is featured in Selected Articles from This Issue, p. 5.

Catastrophic Antiphospholipid Syndrome: A Complex Diagnosis in the Setting of Lupus.

This case report aims to highlight the importance of keeping catastrophic antiphospholipid syndrome (CAPS) high on the list of differentials in patients with lupus who present with digital ischemia and to understand the workup and treatment of the disease. Catastrophic antiphospholipid syndrome is a life-threatening variant of antiphospholipid syndrome (APS), and it is distinguished on the APS spectrum by its increased intensity and extent of thrombotic outcomes. Less than 1% of patients with APS develop CAPS and the demographic of patients affected are primarily females, 37 ± 14 years old, and have underlying primary APS or systemic lupus erythematosus (SLE). This is the case of a young female with lupus and end-stage renal disease secondary to lupus nephritis who presented to the emergency department for shortness of breath and bilateral leg swelling that eventually progressed to catastrophic antiphospholipid syndrome. She developed pulmonary embolisms, axillary hematoma, and bilateral lower extremity digital gangrene. The treatment course consisted of anticoagulation, steroids, intravenous immunoglobulin (IVIG), above-knee amputation, and eventually rituximab. Diagnosis and treatment of digital ischemia can be complex, especially, in the setting of lupus where the differential diagnosis is broad. A high index of suspicion for CAPS is essential for early diagnosis and treatment.

Smoking Cessation Interventions Among Asian Americans: a Scoping Review.

BACKGROUND: Tobacco use is the leading cause of morbidity and mortality in the USA, with smoking rates remaining disproportionately high among Asian-Americans, particularly in males with limited English proficiency, including Vietnamese (43%), Korean (37%), and Chinese (29%) Americans. Barriers to smoking cessation in this population include high social acceptability of smoking in participants' countries of origin, low quit intention, and limited use of linguistically appropriate smoking cessation resources. This paper aims to conduct a systematic review of studies evaluating the effectiveness of smoking cessation interventions targeting Asian-Americans. METHODS: The researchers conducted a thorough search of Scopus, Medline, Cochrane Central, and Google Scholar from 2006 through March 2022, as well as reference lists of relevant articles. The inclusion criteria for the studies were that they described smoking cessation interventions for Asian-Americans and Asian immigrants, and reported outcomes related to feasibility, acceptability, usability, and smoking-related outcomes. RESULTS: The review identified 14 studies with a total of 5607 participants, with participant numbers ranging from 26 to 2277. The interventions varied across 14 distinct approaches, with individual counseling being a prominent component. These interventions were found to be feasible and culturally acceptable. All studies reported positive smoking-related outcomes, including abstinence rates ranging from 26.7 to 68% and an increase in quit attempts. Culturally sensitive components and linguistically tailored content played a significant role in promoting participant engagement. The retention rates in the studies ranged from 42 to 100%, highlighting the importance of partnership with the Asian community, cultural and ethnic congruence, and family involvement and support. CONCLUSION: The review highlighted the lack of direct in-language treatment as a disadvantage for Asian-American smokers in accessing evidence-based treatments. Despite this, the review reported the feasibility, acceptability, and effectiveness of a limited number of culturally targeted interventions for Asian-Americans, who are the fastest-growing racial-ethnic group. Future research should focus on exploring novel community-based and culturally adapted approaches for hard-to-reach and high-risk ethnic Asian subgroups to further improve smoking cessation outcomes in this population.

Base Editor Scanning Reveals Activating Mutations of DNMT3A.

DNA methyltransferase 3A (DNMT3A) is a de novo cytosine methyltransferase responsible for establishing proper DNA methylation during mammalian development. Loss-of-function (LOF) mutations to DNMT3A, including the hotspot mutation R882H, frequently occur in developmental growth disorders and hematological diseases, including clonal hematopoiesis and acute myeloid leukemia. Accordingly, identifying mechanisms that activate DNMT3A is of both fundamental and therapeutic interest. Here, we applied a base editor mutational scanning strategy with an improved DNA methylation reporter to systematically identify DNMT3A activating mutations in cells. By integrating an optimized cellular recruitment strategy with paired isogenic cell lines with or without the LOF hotspot R882H mutation, we identify and validate three distinct hyperactivating mutations within or interacting with the regulatory ADD domain of DNMT3A, nominating these regions as potential functional target sites for pharmacological intervention. Notably, these mutations are still activating in the context of a heterozygous R882H mutation. Altogether, we showcase the utility of base editor scanning for discovering functional regions of target proteins.

GTP signaling links metabolism, DNA repair, and responses to genotoxic stress.

How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links metabolism to DNA repair and has significant therapeutic implications. GTP, but not other nucleotides, regulates the activity of Rac1, a G protein, that promotes the dephosphorylation of serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5). Dephosphorylated Abi-1, a protein previously not known to activate DNA repair, promotes non-homologous end joining. In patients and mouse models of glioblastoma, Rac1 and dephosphorylated Abi-1 mediate DNA repair and resistance to standard of care genotoxic treatments. The GTP-Rac1-PP5-Abi-1 signaling axis is not limited to brain cancer, as GTP supplementation promotes DNA repair and Abi-1-S323 dephosphorylation in non-malignant cells and protects mouse tissues from genotoxic insult. This unexpected ability of GTP to regulate DNA repair independently of deoxynucleotide pools has important implications for normal physiology and cancer treatment.

Older adults and social prescribing experience, outcomes, and processes: a meta-aggregation systematic review.

OBJECTIVE: Social prescribing is a complex care model, which aims to address unmet non-medical needs and connect people to community resources. The purpose of this systematic review was to synthesize available evidence from qualitative methods (e.g. interviews or focus groups) on experience, outcomes, and processes for social prescribing and older adults (from the person or provider level). STUDY DESIGN: This was a systematic review using the Joanna Brigg's meta-aggregative approach. METHODS: We searched multiple online databases for peer-reviewed studies, which included older adults aged ≥60 years (group mean age) and social prescribing experience, outcomes, or processes. We included all qualitative or mixed methods designs from all years and languages. Date of the last primary search was March 24, 2022. Two authors used online software to conduct the screening independently and then decided on the final list of included studies via notes and online discussion. RESULTS: We screened 376 citations (after duplicates) and included eight publications. There were 197 older adult participants (59% women), and many people were living with chronic health conditions. Few details were provided for participants' ethnicity, education, and related factors. We created five synthesized findings related to (1) the approach of social prescribing; implementation factors such as (2) relationships, (3) behavior change strategies, and (4) the environment; and (5) older adults' perceived health and psychosocial outcomes. CONCLUSIONS: Despite the limited number of available studies, data provide an overview of people and processes involved with social prescribing, identified research and practice gaps, and possible next steps for implementing and evaluating social prescribing for older adults in primary care.

Imaging and analysis for simultaneous tracking of fluorescent biosensors in barcoded cells.

We recently developed a biosensor barcoding approach for highly multiplexed tracking of molecular activities in live cells. In this protocol, we detail the labeling of cells expressing different genetically encoded fluorescent biosensors with a pair of barcoding proteins and parallel imaging. Signals from cells with the same barcodes are then pooled together to obtain the dynamics of the corresponding biosensor activity. We describe the steps involved in cell barcoding, image acquisition, and analysis by deep learning models. For complete details on the use and execution of this protocol, please refer to Yang et al. (2021).

Prevagen®: Analysis of Clinical Evidence and Its Designation as a "#1 Pharmacist Recommended Brand".

Prevagen® is a dietary supplement that is marketed to help with mild memory loss associated with older people. The manufacturer of the product notes that clinical evidence supports this use. Furthermore, the manufacturer notes that Prevagen® is a "#1 Pharmacist Recommended Brand." The authors' search of the literature identified one clinical study that evaluated the efficacy and safety of Prevagen®; however, this study possesses significant limitations and therefore one must question the merits of such clinical evidence. Prevagen®'s designation as a "#1 Pharmacist Recommended Brand" is based on a survey facilitated by Pharmacy Times® that is designed to identify the brand name over-the-counter products that pharmacists recommend most frequently. Because of the limited clinical data supporting Prevagen®'s efficacy, it is likely that the survey results reflect pharmacists' familiarity with this product, which may be influenced by extensive advertising techniques. As practitioners of evidence-based medicine, pharmacists should not recommend a product with limited evidence to support its use. Furthermore, pharmacists should proactively educate their patients, especially those who are most vulnerable, about the rational use of all pharmacologically active substances, including dietary supplements.

"There were no words": Older LGBTQ+ persons' experiences of finding and claiming their gender and sexual identities.

This article explores how older Canadian LGBTQ+ persons' gender and sexual identities evolved over time and were influenced by language, role models, and significant others. We draw on data from a qualitative interview study with 30 LGBTQ+ older adults. We analyze our data thematically, finding three overarching themes, namely: a) Lacking language and role models, b) Drawn and pushed out of the closet, and c) Current fluidities and future concerns. Our participants reported that, earlier in life, they had lacked language or positive frameworks with which to make sense of their identities. Upon finding language and role models, all but one eventually came out or transitioned, often after consulting trusted others, experimenting in secret, leading double lives, and/or finding same-sex love. Many were fearful that as they aged, they might once again lose their abilities to openly claim their gender and sexual identities. We discuss our findings in relation to queer theory and the LGBTQ+ aging literature.

Deciphering cell signaling networks with massively multiplexed biosensor barcoding.

Genetically encoded fluorescent biosensors are powerful tools for monitoring biochemical activities in live cells, but their multiplexing capacity is limited by the available spectral space. We overcome this problem by developing a set of barcoding proteins that can generate over 100 barcodes and are spectrally separable from commonly used biosensors. Mixtures of barcoded cells expressing different biosensors are simultaneously imaged and analyzed by deep learning models to achieve massively multiplexed tracking of signaling events. Importantly, different biosensors in cell mixtures show highly coordinated activities, thus facilitating the delineation of their temporal relationship. Simultaneous tracking of multiple biosensors in the receptor tyrosine kinase signaling network reveals distinct mechanisms of effector adaptation, cell autonomous and non-autonomous effects of KRAS mutations, as well as complex interactions in the network. Biosensor barcoding presents a scalable method to expand multiplexing capabilities for deciphering the complexity of signaling networks and their interactions between cells.

Concentration effects of three common fish anesthetics on Pacific hagfish (Eptatretus stoutii).

The efficacy of three common fish anesthetics (clove oil, 2-phenoxyethanol, and tricaine methanesulfonate) was evaluated in the Pacific hagfish (Eptatretus stoutii). The overarching aim of our study was to identify the best anesthetic and concentration for the purposes of routine laboratory use of Pacific hagfish (i.e., short and consistent induction and recovery times and minimized stress and safety risk to hagfish). The objectives of our study were fourfold: (1) identify anesthetic stages of Pacific hagfish using clove oil anesthesia; (2) establish standardized anesthesia preparation procedures; (3) determine the optimal anesthetic and concentration for safely achieving stage V anesthesia; and (4) investigate the effects of repeatedly exposing Pacific hagfish to anesthesia. Experimental concentrations, ranging from 50 to 400 mg/L, of each anesthetic were tested on at least three Pacific hagfish individuals. We found the following: (1) Pacific hagfish exhibited similar stages of anesthesia to those described for bony fishes; (2) sufficient mixing of clove oil with seawater had a considerable effect on the consistency and timing of anesthetic induction; (3) concentration and anesthetic significantly impacted induction and recovery timing, whereas body mass had no impact on anesthetic trends; and (4) repeatedly exposing Pacific hagfish to optimal concentrations of clove oil or MS-222 had no effect on induction or recovery timing, whereas exposure number significantly impacted induction timing when using 2-PE. Due to consistent induction and recovery times, low risk of accidental overdose, and high safety margins for both handler and hagfish, we recommend 175 mg/L of clove oil as the ideal anesthetic and concentration for the routine laboratory use of Pacific hagfish.

Family and Friend Influences on Fruit and Vegetable Intake in Elementary Aged Children.

The purpose of this study was to investigate the eating behaviors and social cognitive factors that affect fruit and vegetable consumption. Strategies to change, pros & cons, enjoyment, family support, and peer influence were measured in children ages 8-10 years both pre- and post- Zest Quest® program (pre: n = 82; post: n = 80). Children for a comparison group were selected from comparable elementary schools and pre- and post- measures were evaluated (pre: n = 92; post: n = 87). Chi-squared analyses were conducted on individual measures and Spearman correlations & linear regression were used for composite variables with fruit and vegetable consumption as the dependent variable. Results from the study demonstrated significant moderate correlations for fruit change strategies pre- (rs = 0.39) and post-intervention (rs = 0.33) and vegetable change strategies pre-intervention (rs = 0.42) in the Zest Quest® group. Peer influence (rs = 0.33) and enjoyment (rs = 0.38) showed significant moderate correlations with fruit intake in the comparison group. The regression analysis showed pros (ß = 0.24, p value 0.05) and cons (ß = 0.14, p value 0.05) to be significant predictors for fruit intake post-intervention in the Zest Quest® group. Prior to the intervention, strategies to change (ß = 0.10, p value 0.02) was a significant predictor for fruit intake and cons (ß = 0.15, p value = 0.03) for vegetable intake in this group. Family support and peer influence were not significant in the regression models, but demonstrated significance in the crude model. Eating behaviors and social cognitive factors may have an effect on fruit and vegetable consumption, but these measures are difficult to capture. Future research should continue exploring the impact of family support and peer influence on fruit and vegetable intake.

Rates and Risk Factors for Post-Traumatic Stress Disorder Symptomatology among Adult Hematopoietic Cell Transplant Recipients and Their Informal Caregivers.

Hematopoietic cell transplant (HCT) can cause significant distress in patients and their informal caregivers. Despite advances in reduced-intensity conditioning and supportive care, few recent studies have reported rates of clinically significant post-traumatic stress disorder (PTSD) symptomatology. Goals of the current study were to examine rates of PTSD and distress in patients and caregivers and to identify sociodemographic and clinical risk factors for PTSD. As part of an annual survivorship survey, 2157 HCT recipients and their caregivers were mailed self-report measures of PTSD and distress. Patients also completed self-report measures of sociodemographic information (eg, age, sex, employment status). Clinical variables (eg, time since transplant, transplant type) were captured in the transplant database. A total of 691 recipients (56% age 60 or above at the time of survey, 47% women, median 10.1 years post-HCT) and 333 caregivers provided PTSD data and were included in the current analyses. More caregivers reported PTSD (6.6%) than patients (3.3%; P = .02). Patients or caregivers who had PTSD reported significantly higher distress related to uncertainty, family strain, medical demands, finances, identity, and health burden (P < .0001) compared with those without PTSD. Patient but not caregiver PTSD was associated with more recent transplant (P = .01 and P = .16, respectively). Rates of PTSD are relatively low in long-term survivors of HCT and their caregivers. Nevertheless, results are consistent with other studies of cancer caregiving suggesting that caregivers often experience greater distress than patients. Timely referral to psychosocial services should be offered to both HCT recipients and caregivers reporting symptoms of PTSD.

Telemedicine and Mobile Health Technology Are Effective in the Management of Digestive Diseases: A Systematic Review.

BACKGROUND: Mobile applications and interactive websites are an increasingly used method of telemedicine, but their use lacks evidence in digestive diseases. AIM: This study aims to explore digestive disease studies that use telemedicine to effectively manage disease activity, help monitor symptoms, improve compliance to the treatment protocol, increase patient satisfaction, and enhance the patient-to-provider communication. METHODS: EBSCO, PubMed, and Web of Science databases were searched using Medical Subject Headings and other keywords to identify studies that utilized telemedicine in patients with digestive disease. The PRISMA guidelines were used to identify 20 research articles that had data aligning with 4 common overlapping themes including, patient compliance (n = 13), patient satisfaction (n = 11), disease activity (n = 15), and quality of life (n = 13). The studies focused on digestive diseases including inflammatory bowel disease (n = 7), ulcerative colitis (n = 4), Crohn's Disease (n = 1), irritable bowel syndrome (n = 6), and colorectal cancer (n = 2). RESULTS: From the studies included in this systematic review, patient compliance and patient satisfaction ranged between 25.7-100% and 74-100%, respectively. Disease activity, measured by symptom severity scales and physiological biomarkers, showed improvements following telemedicine interventions in several, but not all, studies. Similar to disease activity, general and disease-specific quality of life showed improvements following telemedicine interventions in as little as 12 weeks in some studies. CONCLUSION: Telemedicine and mobile health technology may be effective in managing disease activity and improving quality of life in digestive diseases. Future studies should explore both gastrointestinal and gastroesophageal diseases using these types of interventions.

Associations Between Parental BMI and the Family Nutrition and Physical Activity Environment in a Community Sample.

The purpose of this study was to examine the relationship between parental BMI and the family environment and determine if differences exist in child diet and physical activity related parenting behaviors by parental BMI in a community sample of families recruited through elementary schools in a local school district. We found an association between parental BMI category and family nutrition and physical activity (FNPA) score. Families with an underweight or normal weight parent had a larger proportion (64.3%) of high (indicating a healthier family environment) FNPA scores and families with an overweight or obese parent had a smaller proportion (45.2%) of high FNPA scores (χ 2 = 5.247, P = 0.022). Families with a parent who was overweight or obese had 2.18 times the odds (95% CI 1.11-4.27) of being in the low FNPA ("less healthy" environment) group. Further, underweight/normal weight parents reported higher levels of monitoring of child diet (Z = -3.652, P < 0.0001), higher levels of parental monitoring of child physical activity (Z = -3.471, p < 0.001), and higher levels of parental limit setting related to child sedentary activities compared to overweight/obese parents (Z = -2.443, P = 0.01). Parent BMI and parenting behaviors are known to have a major impact on childhood obesity. In this study, lower parent BMI and authoritative parenting behaviors were associated with a less obesogenic home environment and a positive parenting style related to child eating and physical activity behaviors.