Building Climate Change into Medical Education: A Society of General Internal Medicine Position Statement.

Building expertise in climate and planetary health among healthcare professionals cannot come with greater urgency as the threats from climate change become increasingly apparent. Current and future healthcare professionals-particularly internists-will increasingly need to understand the interconnectedness of natural systems and human health to better serve their patients longitudinally. Despite this, few national medical societies and accreditation bodies espouse frameworks for climate change and planetary health-related education at the undergraduate (UME), graduate (GME), and continuing (CME) medical education level. As a community of medical educators with an enduring interest in climate change and planetary health, the Society of General Internal Medicine (SGIM) recognizes the need to explicitly define structured educational opportunities and core competencies in both UME and GME as well as pathways for faculty development. In this position statement, we build from the related SGIM Climate and Health position statement, and review and synthesize existing position statements made by US-based medical societies and accreditation bodies that focus on climate change and planetary health-related medical education, identify gaps using Bloom's Hierarchy, and provide recommendations on behalf of SGIM regarding the development of climate and planetary health curricula development. Identified gaps include (1) limited systematic approach to climate and planetary health medical education at all levels; (2) minimal emphasis on learner-driven approaches; (3) limited focus on physician and learner well-being; and (4) limited role for health equity and climate justice. Recommendations include a call to relevant accreditation bodies to explicitly include climate change and planetary health as a competency, extend the structural competency framework to climate change and planetary health to build climate justice, proactively include learners in curricular development and teaching, and ensure resources and support to design and implement climate and planetary health-focused education that includes well-being and resiliency.

A connection between the ribosome and two S. pombe tRNA modification mutants subject to rapid tRNA decay.

tRNA modifications are crucial in all organisms to ensure tRNA folding and stability, and accurate translation. In both the yeast Saccharomyces cerevisiae and the evolutionarily distant yeast Schizosaccharomyces pombe, mutants lacking certain tRNA body modifications (outside the anticodon loop) are temperature sensitive due to rapid tRNA decay (RTD) of a subset of hypomodified tRNAs. Here we show that for each of two S. pombe mutants subject to RTD, mutations in ribosomal protein genes suppress the temperature sensitivity without altering tRNA levels. Prior work showed that S. pombe trm8Δ mutants, lacking 7-methylguanosine, were temperature sensitive due to RTD, and that one class of suppressors had mutations in the general amino acid control (GAAC) pathway, which was activated concomitant with RTD, resulting in further tRNA loss. We now find that another class of S. pombe trm8Δ suppressors have mutations in rpl genes, encoding 60S subunit proteins, and that suppression occurs with minimal restoration of tRNA levels and reduced GAAC activation. Furthermore, trm8Δ suppression extends to other mutations in the large or small ribosomal subunit. We also find that S. pombe tan1Δ mutants, lacking 4-acetylcytidine, are temperature sensitive due to RTD, that one class of suppressors have rpl mutations, associated with minimal restoration of tRNA levels, and that suppression extends to other rpl and rps mutations. However, although S. pombe tan1Δ temperature sensitivity is associated with some GAAC activation, suppression by an rpl mutation only modestly inhibits GAAC activation. We propose a model in which ribosomal protein mutations result in reduced ribosome concentrations, leading to both reduced ribosome collisions and a reduced requirement for tRNA, with these effects having different relative importance in trm8Δ and tan1Δ mutants. This model is consistent with our results in S. cerevisiae trm8Δ trm4Δ mutants, known to undergo RTD, fueling speculation that this model applies across eukaryotes.

A connection between the ribosome and two S. pombe tRNA modification mutants subject to rapid tRNA decay.

tRNA modifications are crucial in all organisms to ensure tRNA folding and stability, and accurate translation in the ribosome. In both the yeast Saccharomyces cerevisiae and the evolutionarily distant yeast Schizosaccharomyces pombe, mutants lacking certain tRNA body modifications (outside the anticodon loop) are temperature sensitive due to rapid tRNA decay (RTD) of a subset of hypomodified tRNAs. Here we show that for each of two S. pombe mutants subject to RTD, mutations in ribosomal protein genes suppress the temperature sensitivity without altering tRNA levels. Prior work showed that S. pombe trm8Δ mutants, lacking 7-methylguanosine, were temperature sensitive due to RTD and that one class of suppressors had mutations in the general amino acid control (GAAC) pathway, which was activated concomitant with RTD, resulting in further tRNA loss. We now find that another class of S. pombe trm8Δ suppressors have mutations in rpl genes, encoding 60S subunit proteins, and that suppression occurs with minimal restoration of tRNA levels and reduced GAAC activation. Furthermore, trm8Δ suppression extends to other mutations in the large or small ribosomal subunit. We also find that S. pombe tan1Δ mutants, lacking 4-acetylcytidine, are temperature sensitive due to RTD, that one class of suppressors have rpl mutations, associated with minimal restoration of tRNA levels, and that suppression extends to other rpl and rps mutations. However, although S. pombe tan1Δ temperature sensitivity is associated with some GAAC activation, suppression by an rpl mutation does not significantly inhibit GAAC activation. These results suggest that ribosomal protein mutations suppress the temperature sensitivity of S. pombe trm8Δ and tan1Δ mutants due to reduced ribosome concentrations, leading to both a reduced requirement for tRNA, and reduced ribosome collisions and GAAC activation. Results with S. cerevisiae trm8Δ trm4Δ mutants are consistent with this model, and fuel speculation that similar results will apply across eukaryotes.

Hypothyroidism in Adult Women: The Utility of Targeted vs Universal Thyroid Screening.

Hypothyroidism is a common disease that is more prevalent in female populations. The purpose of this paper is to discuss the evidence, risks, and benefits of screening asymptomatic women for hypothyroidism. There is lack of evidence to support clinical management of asymptomatic individuals with an elevated TSH and normal serum thyroxine levels. Patients with subclinical hypothyroidism, especially the elderly, are at risk of overtreatment. Given these considerations, the majority of US and UK professional organizations do not support universal screening. Many do offer caveats for special groups, including pregnant people, who may need screening if there are clinical symptoms or family history of autoimmune disease. In conclusion, targeted screening may be best recommended based on risk factors, symptoms, and clinical suspicion, rather than at a universal level.

Primary hypothyroidism and chronotypes in adult women.

OBJECTIVE: Abnormal thyroid function may disrupt sleep architecture. We aimed to determine the frequency of various chronotypes in women with hypothyroidism. We performed a single-center retrospective study at an ambulatory clinic from January 2013-December 2015. Participants were women with hypothyroidism. Chronotype was determined from the Munich ChronoType Questionnaire. The χ2 test was used to compare differences in clinical characteristics and sleep patterns in early and intermediate/late chronotypes. The t test was used to compare differences between means. RESULTS: We evaluated 99 patients (mean [SD], 56 [7] years): calculated chronotype revealed: 56% early, 38% intermediate and 6% late. Analysis with the χ2 test showed significant differences between early and intermediate/late calculated chronotypes for sleep latency (P = 0.01), light exposure (P = 0.009), and no alcohol intake (P = 0.001). t test showed the following differences in mean (SD) between chronotypes: sleep duration, 7.30 (1.39) hours (early chronotype) and 7.04 (2.06) hours (intermediate/late); body mass index (BMI), 29.4 (7.3) (early) and 31.1 (6.8) (intermediate/late); and TSH level, 2.89 (3.69) mIU/L (early) and 1.69 (1.41) mIU/L (intermediate/late). Early chronotypes were frequent in women with hypothyroidism. Light exposure and BMI may influence chronotypes in patients with hypothyroidism; findings are consistent with healthier behaviors in patients who tend toward morningness.

Perception of Breast Density Information Among Women in Miami, FL: a Qualitative Study.

The US Food and Drug Administration has proposed requiring that all women undergoing mammography receive written information about their breast density. Past research suggests many women may misperceive the meaning of breast density. Additionally, women with dense breasts may not understand the risks and benefits of pursuing additional imaging studies. The goal of this study was to explore women's beliefs about breast density and their preferences for how this information is conveyed. Women with increased breast density detected on mammography at a university-based breast imaging center in South Florida were recruited for a series of focus groups. Twenty-five women participated, ranging in age from 42 to 65 years. Nine women (36%) self-identified as Hispanic/Latina, eight (32%) as Black, four (16%) as White, three (12%) as Asian, and one as "other." Four focus groups were conducted in English and one in Spanish by professional moderators using a semi-structured format. A constant comparative method was used to identify common themes using a general inductive approach. Areas explored included understanding of the term breast density; personal reaction to being informed of dense breasts; questions about breast density; understanding of supplemental screening; and preferences for how to convey breast density information. Subthemes identified included a misperception that breast density is palpable; a feeling of fear on learning of increased breast density results; a concern about what causes increased breast density and whether it can be reversed; a desire to proceed with supplemental ultrasound imaging; and a preference for simple messages explaining the concept of breast density in multiple formats including video. Participants voiced the incorrect belief that caffeine intake could increase breast density and stated that they wanted to know specific details about their personal results. There is a need for better tools to communicate breast density in a way that allays anxiety while enabling women to make fully informed decisions about their breast health. Clinicians and cancer educators should be aware of misperceptions women may have about breast density. Policymakers should keep in mind potential public confusion about this complex topic when crafting density notification rules.

A semi-quantitative pull-down assay to study tRNA substrate specificity of modification enzymes.

A tRNA interacts with numerous proteins throughout its biogenesis and during translation, and a significant portion of these interacting proteins are involved in post-transcriptional modifications. While some of the modifying enzymes use relatively simple recognition elements for substrate recognition, many enzymes selectively modify a specific subset of tRNA species without obvious recognition rules. In this chapter we describe a semi-quantitative pull-down assay to study tRNA substrate specificity of modification enzymes, by using the yeast Saccharomyces cerevisiae m3C32 methyltransferase Trm140 as an example. We also discuss some overall considerations for a successful pull-down experiment, with a focus on practical applications of the dissociation constant KD between the protein and the tRNA and the off-rate.

How Does Black History Help Doctors? Addressing Cultural Competency through Cinemeducation at a Diverse Medical School.

ABSTRACT: Racial minorities will account for >50% of the United States population by 2045, yet race and ethnicity persist as leading predictors of morbidity. Although minorities achieve better outcomes when treated by racially concordant providers, the number of minority physicians is disproportionately low compared with the rapidly growing minority population. This imbalance creates a cultural gap between many minority patients and their healthcare providers. Research suggests that educational initiatives addressing health inequity through a historical lens can help providers better understand the root causes of disparities; however, extensive clinical demands severely limit the time providers can dedicate to non-medical learning. OBJECTIVES: To address this gap, the University of Miami/Jackson Memorial Hospital System developed and piloted a short film about the history of Black people in South Florida, highlighting significant events that shaped the health-seeking behaviors of this population. METHODS: A 20-minute documentary exploring the sociocultural history of Black communities in Miami-Dade County was presented to 188 first-year postgraduate residents in June 2017. Residents completed pre-post surveys to measure changes in knowledge and care delivery intentions. RESULTS: Analyses performed between March and July 2018 revealed moderate improvements in the knowledge and awareness of the socioeconomic history of Miami's Black communities. Before watching the video, a majority indicated that increasing awareness of the sociocultural history of their patient population was a valuable learning activity. CONCLUSIONS: These findings suggest that brief videos focused on the history of culturally distinct populations may be a successful pedagogical strategy to introduce physicians to the communities they serve and improve provider knowledge.

Seizure Disorder Exacerbated by Hepatic Encephalopathy: A Case Report.

BACKGROUND: Hepatic encephalopathy is a serious complication of cirrhosis that presents with a variety of neuropsychiatric abnormalities, including disorientation, asterixis, and coma. Seizures are an uncommon and potentially dangerous complication of hepatic encephalopathy. We present a unique case of a 42-year-old female with a history of well-controlled seizure disorder suddenly become refractory to anticonvulsant therapy following the development of hepatic encephalopathy secondary to liver decompensation. CASE PRESENTATION: A 42-year-old female presented to our hospital following a seizure accompanied by loss of consciousness, urinary incontinence, and the prolonged postictal state. She reports her seizures were initially well-controlled with Levetiracetam 500 mg twice a day but recently began experiencing seizures every other day despite up-titration of Levetiracetam to 1500 mg twice a day over a few weeks. On arrival, her serum ammonia level was 116 µmol/L. CT brain was negative while CT liver was consistent with cirrhotic morphology. An electroencephalogram revealed irregular, diffuse, delta/theta slowing consistent with mild to moderate encephalopathy. The patient was started on lactulose 40mg and Rifaximin 550 mg twice a day. Her symptoms of disorientation and lethargy resolved over 3 days. CONCLUSION: Though uncommon, hepatic encephalopathy should be considered in patients presenting with convulsions, especially if there is a known history of liver disease. Until the underlying liver issues are addressed, patients may not respond to traditional anti-convulsant therapy for their seizures.

A Brochure to Improve Understanding of Incomplete Mammogram Results Among Black Women at a Public Hospital in Miami, Florida.

OBJECTIVES: Black women are at increased risk of being called back for additional studies after a screening mammogram. With focus group input, we developed a brochure to improve awareness of the frequency of abnormal results. This study explored the brochure's acceptability and effect on understanding risk and breast cancer fears among black mammography patients at an urban safety-net breast imaging center in Miami, Florida. METHODS: A randomized controlled trial of the brochure (plus the standard result notification letter) versus usual care (standard notification letter alone). Black English-speaking women with an incomplete mammography result were randomized to the intervention or control group. Consenting participants completed a telephone questionnaire. Outcomes included awareness of result, anxiety level, and brochure acceptability. The χ2 or Fisher exact test was used and a univariate logistic regression was performed for intervention and control odds ratios. RESULTS: A total of 106 women were randomly selected to receive the brochure plus the letter or the letter alone. One chose to opt out; a minimum of three attempts were made to reach each of the remaining 105 women by telephone. Verbal communication was established with 59 of the randomized women, and 51 of those women agreed to participate in a survey to evaluate the brochure. There was no significant difference between the surveyed groups in knowledge of the result and follow-up plan. Surveyed intervention subjects were more likely to agree that "it is very common for women to have to follow up after a mammogram" (odds ratio [OR] 25.91, P = 0.029) and less likely to agree with the statement "getting a follow-up mammogram is scary" (OR 0.24, P = 0.021). Most intervention subjects said the pamphlet helped them understand their result "a lot" (79%, 19) and viewed it as "extremely" or "mostly" clear (96%, 23). Intervention subjects also voiced greater awareness of a telephone number they could call for more information about cancer (OR 11.38, P = 0.029). CONCLUSIONS: A culturally tailored brochure explaining the frequency of abnormal mammograms was well received by women at a large safety-net health system. Pilot testing suggests that it may improve patient perception of risk and awareness of informational resources. This strategy should be considered to enhance result communication.

Glycaemic indices and haemoglobin A1c as predictors for non-healing ulcers.

OBJECTIVE: Non-healing lower extremity ulcers (NHLU) are a common podiatric complication of diabetes, with poor glycaemic control as a risk factor for development. Glycaemic indices, such as haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG), are used to diagnose and to monitor diabetes. Using a population-based, nationally representative sample, we evaluate the relationship between glycaemic indices and NHLU (as defined by the patient) to propose glycaemic thresholds for clinical suspicion of patient NHLU status. METHOD: Using data from the 1999-2004 National Health and Nutrition Examination Surveys (NHANES), a total of 9769 adults (≥40 years old) with available self-reported diabetes and NHLU status were analysed. Glycaemic index markers, including FPG and HbA1c, were assessed via laboratory analysis from serum blood samples. Logistic regression models were fitted to determine optimal thresholds for FPG and HbA1c to predict NHLU status. RESULTS: Compared with those without NHLU, NHLU patients were older, male, had higher rates of diabetes, were more likely to take insulin, and had lower total cholesterol. Youden's Index for NHLU identified the optimal FPG threshold as 117.7mg/dl (sensitivity: 33.5%; specificity: 82.6%). The optimal HbA1c threshold was 5.9% (sensitivity: 43.2%; specificity: 77.3%). HbA1c (Odds ratio (OR) 2.44, 95% Confidence Interval (CI) 1.96-3.05; Area under curve (AUC) 0.62) was a stronger discriminator of NHLU compared to FPG (OR 2.19; 95%CI 1.57-3.05; AUC 0.60). CONCLUSION: This study identified glycaemic thresholds for suspicion of NHLU development that are lower than the glucose goal levels recommended as optimal by the American Diabetes Association. Health professionals should be aware of these glycaemic indices when screening patients with diabetes for NHLU. Future longitudinal and validation studies are necessary to better discern the ideal glycaemic index thresholds to identify NHLU.

Minority Veterans Are More Willing to Participate in Complex Studies Compared to Non-minorities.

BACKGROUND: Minorities are an underrepresented population in clinical trials. A potential explanation for this underrepresentation could be lack of willingness to participate. The aim of our study was to evaluate willingness to participate in different hypothetical clinical research scenarios and to evaluate the role that predictors (e.g. health literacy) could have on the willingness of minorities to participate in clinical research studies. METHODS: We conducted a mixed-methods study at the Miami VA Healthcare system and included primary care patients with hypertension. We measured willingness to participate as a survey of four clinical research scenarios that evaluated common study designs encountered in clinical research and that differed in degree of complexity. Our qualitative portion included comments about the scenarios. RESULTS: We included 123 patients with hypertension in our study. Of the entire sample, ninety-three patients were minorities. Seventy per cent of the minorities were willing to participate, compared to 60 per cent of the non-minorities. The odds ratio (OR) of willingness to participate in simple studies was 0.58; 95 per cent CI 0.18-1.88 p=0.37 and the OR of willingness to participate in complex studies was 5.8; 95 per cent CI 1.10-1.31 p=0.03. In complex studies, minorities with low health literacy cited obtaining benefits (47 per cent) as the most common reason to be willing to participate. Minorities who were not willing to participate, cited fear of unintended outcomes as the main reason. CONCLUSIONS: Minorities were more likely to be willing to participate in complex studies compared to non-minorities. Low health literacy and therapeutic misconception are important mediators when considering willingness to participate in clinical research.

High-Throughput Small RNA Sequencing Enhanced by AlkB-Facilitated RNA de-Methylation (ARM-Seq).

N 1-methyladenosine (m1A), N 3-methylcytidine (m3C), and N 1-methylguanosine (m1G) are common in transfer RNA (tRNA) and tRNA-derived fragments. These modifications alter Watson-Crick base-pairing, and cause pauses or stops during reverse transcription required for most high-throughput RNA sequencing protocols, resulting in inefficient detection of methyl-modified RNAs. Here, we describe a procedure to demethylate RNAs containing m1A, m3C, or m1G using the Escherichia coli dealkylating enzyme AlkB, along with instructions for subsequent processing with widely used protocols for small RNA sequencing.

S. cerevisiae Trm140 has two recognition modes for 3-methylcytidine modification of the anticodon loop of tRNA substrates.

The 3-methylcytidine (m3C) modification is ubiquitous in eukaryotic tRNA, widely found at C32 in the anticodon loop of tRNAThr, tRNASer, and some tRNAArg species, as well as in the variable loop (V-loop) of certain tRNASer species. In the yeast Saccharomyces cerevisiae, formation of m3C32 requires Trm140 for six tRNA substrates, including three tRNAThr species and three tRNASer species, whereas in Schizosaccharomyces pombe, two Trm140 homologs are used, one for tRNAThr and one for tRNASer The occurrence of a single Trm140 homolog is conserved broadly among Ascomycota, whereas multiple Trm140-related homologs are found in metazoans and other fungi. We investigate here how S. cerevisiae Trm140 protein recognizes its six tRNA substrates. We show that Trm140 has two modes of tRNA substrate recognition. Trm140 recognizes G35-U36-t6A37 of the anticodon loop of tRNAThr substrates, and this sequence is an identity element because it can be used to direct m3C modification of tRNAPhe However, Trm140 recognition of tRNASer substrates is different, since their anticodons do not share G35-U36 and do not have any nucleotides in common. Rather, specificity of Trm140 for tRNASer is achieved by seryl-tRNA synthetase and the distinctive tRNASer V-loop, as well as by t6A37 and i6A37 We provide evidence that all of these components are important in vivo and that seryl-tRNA synthetase greatly stimulates m3C modification of tRNASer(CGA) and tRNASer(UGA) in vitro. In addition, our results show that Trm140 binding is a significant driving force for tRNA modification and suggest separate contributions from each recognition element for the modification.

Acceptability and Feasibility of Human Papilloma Virus Self-Sampling for Cervical Cancer Screening.

OBJECTIVES: Women in safety-net institutions are less likely to receive cervical cancer screening. Human papilloma virus (HPV) self-sampling is an alternative method of cervical cancer screening. We examine the acceptability and feasibility of HPV self-sampling among patients and clinic staff in two safety-net clinics in Miami. MATERIALS AND METHODS: Haitian and Latina women aged 30-65 years with no Pap smear in the past 3 years were recruited. Women were offered HPV self-sampling or traditional Pap smear screening. The acceptability of HPV self-sampling among patients and clinic staff was assessed. If traditional screening was preferred the medical record was reviewed. RESULTS: A total of 180 women were recruited (134 Latinas and 46 Haitian). HPV self-sampling was selected by 67% women. Among those selecting traditional screening, 22% were not screened 5 months postrecruitment. Over 80% of women agreed HPV self-sampling was faster, more private, easy to use, and would prefer to use again. Among clinic staff, 80% agreed they would be willing to incorporate HPV self-sampling into practice. CONCLUSIONS: HPV self-sampling was both acceptable and feasible to participants and clinic staff and may help overcome barriers to screening.