SRSF2 plays an unexpected role as reader of m5C on mRNA, linking epitranscriptomics to cancer.

A common mRNA modification is 5-methylcytosine (m5C), whose role in gene-transcript processing and cancer remains unclear. Here, we identify serine/arginine-rich splicing factor 2 (SRSF2) as a reader of m5C and impaired SRSF2 m5C binding as a potential contributor to leukemogenesis. Structurally, we identify residues involved in m5C recognition and the impact of the prevalent leukemia-associated mutation SRSF2P95H. We show that SRSF2 binding and m5C colocalize within transcripts. Furthermore, knocking down the m5C writer NSUN2 decreases mRNA m5C, reduces SRSF2 binding, and alters RNA splicing. We also show that the SRSF2P95H mutation impairs the ability of the protein to read m5C-marked mRNA, notably reducing its binding to key leukemia-related transcripts in leukemic cells. In leukemia patients, low NSUN2 expression leads to mRNA m5C hypomethylation and, combined with SRSF2P95H, predicts poor outcomes. Altogether, we highlight an unrecognized mechanistic link between epitranscriptomics and a key oncogenesis driver.

COVID-19 Outbreaks and Mortality Among Public Transportation Workers - California, January 2020-May 2022.

Work-related factors can contribute to risk for exposure to and infection with SARS-CoV-2, the virus that causes COVID-19, and subsequent COVID-19-attributable outcomes, including death. Comparing COVID-19 metrics across industries can help identify workers at highest risk. Elevated COVID-19 mortality rates have been reported among all transportation workers, as well as specifically in public transportation industries (1-3). The California Department of Public Health (CDPH) calculated public transportation industry-specific COVID-19 outbreak incidence during January 2020-May 2022 and analyzed all laboratory-confirmed COVID-19 deaths among working-age adults in California to calculate public transportation industry-specific mortality rates during the same period. Overall, 340 confirmed COVID-19 outbreaks, 5,641 outbreak-associated cases, and 537 COVID-19-associated deaths were identified among California public transportation industries. Outbreak incidence was 5.2 times as high (129.1 outbreaks per 1,000 establishments) in the bus and urban transit industry and 3.6 times as high in the air transportation industry (87.7) as in all California industries combined (24.7). Mortality rates were 2.1 times as high (237.4 deaths per 100,000 workers) in transportation support services and 1.8 times as high (211.5) in the bus and urban transit industry as in all industries combined (114.4). Workers in public transportation industries are at higher risk for COVID-19 workplace outbreaks and mortality than the general worker population in California and should be prioritized for COVID-19 prevention strategies, including vaccination and enhanced workplace protection measures.

Clinical Results of Ultrasound-Guided Carpal Tunnel Release Performed by a Primary Care Sports Medicine Physician.

OBJECTIVES: The purpose of this study was to determine the safety and efficacy of ultrasound-guided carpal tunnel release (USCTR) in a consecutive group of patients treated by a single primary care sports medicine physician. METHODS: The study group consisted of 35 USCTRs performed on 22 consecutive patients for whom clinical outcomes were available before USCTR and at 1 to 2 weeks, 1 month, and 3 months after USCTR. All procedures were performed by the same operator using a single USCTR technique. Outcomes included complications, Quick Disabilities of the Arm, Shoulder, and Hand scores, Boston Carpal Tunnel Questionnaire symptom severity and functional status scores, and a 5-point global satisfaction score. RESULTS: The 22 patients included 13 female and 9 male patients (ages 31-82 years). Eleven patients (22 wrists) had bilateral simultaneous USCTRs; 2 patients (4 wrists) had staged bilateral USCTRs; and 9 patients had unilateral USCTRs. No complications occurred in any patient. Statistically and clinically significant reductions in Quick Disabilities of the Arm, Shoulder, and Hand scores and Boston Carpal Tunnel Questionnaire symptom severity and functional status scores occurred by 1 to 2 weeks after USCTR (mean 1- to 2-week changes, -29.23, -1.74, and -1.18, respectively), and further improvements occurred during the 3-month follow-up period (mean 3-month changes, -51.11, -2.29, and -1.91; P < .0001 for all values versus before USCTR). Mean global satisfaction scores at 1 to 2 weeks and 3 months were 4.63 and 4.66. CONCLUSIONS: Ultrasound-guided CTR is a safe and effective procedure that can be performed by an experienced primary care sports medicine physician and typically results in significant improvements within the first 2 weeks after the procedure. Furthermore, bilateral simultaneous USCTRs are feasible and may provide significant advantages for patients who are candidates for bilateral CTRs.

Ultrasound (US) Changes in the Median Nerve Cross-Sectional Area After Microinvasive US-Guided Carpal Tunnel Release.

OBJECTIVE: To document changes in the median nerve cross-sectional area (CSA) in the proximal carpal tunnel region after ultrasound (US)-guided carpal tunnel release (CTR). METHODS: Prospective data were collected on 23 consecutive patients (37 wrists) treated with US-guided CTR by the primary author using the same office-based microinvasive technique. Ultrasound was used to measure the largest CSA of the median nerve in the proximal carpal tunnel region both preoperatively and postoperatively. The primary outcome measure was the change in the preoperative versus 6- to 10-week postoperative median nerve CSA. RESULTS: The mean CSA of the median nerve decreased from 16.08 to 12.75 mm2 at 6 to 10 weeks after US-guided CTR (P < .001). During the same period, the mean Boston Carpal Tunnel Questionnaire (BCTQ) symptom score decreased from 3.23 to 1.67 (P < .001), and mean BCTQ functional score decreased from 2.49 to 1.47 (P < .001), both exceeding minimal clinically important differences. Although the primary end point was the median nerve CSA at 6 to 10 weeks, statistically significant reductions in the median nerve CSA, as well as BCTQ scores, were also observed as early as 2 to 4 weeks after US-guided CTR (median nerve CSA, 12.40 mm2 ; BCTQ symptom score, 2.00; BCTQ functional score, 1.75; all P ≤ .03). CONCLUSIONS: To our knowledge, this investigation was the largest to date examining changes in the proximal median nerve CSA after US-guided CTR. Statistically significant reductions in the proximal median nerve CSA were observed within 6 to 10 weeks after ultrasound-guided CTR. These reductions were similar to those previously reported for open and endoscopic CTR and validate the ability of US-guided CTR to relieve median nerve compression.

Restoration of cellular integrity following "ballistic" pronuclear exchange during Tetrahymena conjugation.

During sexual reproduction or conjugation, ciliates form a specialized cell adhesion zone for the purpose of exchanging gametic pronuclei. Hundreds of individual membrane fusion events transform the adhesion zone into a perforated membrane curtain, the mating junction. Pronuclei from each mating partner are propelled through this fenestrated membrane junction by a web of short, cris-crossing microtubules. Pronuclear passage results in the formation of two breaches in the membrane junction. Following pronuclear exchange and karyogamy (fertilization), cells seal these twin membrane breaches thereby re-establishing cellular independence. This would seem like a straightforward problem: simply grow membrane in from the edges of each breach in a fashion similar to how animal cells "grow" their cytokinetic furrows or how plant cells construct a cell wall during mitosis. Serial section electron microscopy and 3-D electron tomography reveal that the actual mechanism is less straightforward. Each of the two membrane breaches transforms into a bowed membrane assembly platform. The resulting membrane protrusions continue to grow into the cytoplasm of the mating partner, traverse the cytoplasm in anti-parallel directions and make contact with the plasma membrane that flanks the mating junction. This investigation reveals the details of a novel, developmentally-induced mechanism of membrane disruption and restoration associated with pronuclear exchange and fertilization in the ciliate, Tetrahymena thermophila.

Rates of Carpal Tunnel Syndrome in a State Workers' Compensation Information System, by Industry and Occupation - California, 2007-2014.

Carpal tunnel syndrome (CTS) occurs when the median nerve becomes compressed as it passes through the wrist within the carpal tunnel, resulting in pain, tingling, weakness, or numbness in the hand or the wrist. Occupational risk factors for CTS include engaging in work activities that require forceful, repetitive tasks, prolonged use of the hands or wrists in an awkward posture, or vibration (1). To assess trends and identify high-risk industries and occupations for CTS, the California Department of Public Health (CDPH) analyzed California workers' compensation claims for CTS by industry (2007-2014) and occupation (2014) and calculated rates per full-time equivalent (FTE) worker. During 2007-2014, a total of 139,336 CTS cases were reported (incidence = 6.3 cases per 10,000 FTE) in California workers; the rate among women (8.2) was 3.3 times higher than that among men (2.5). Industries with the highest rates of CTS were textile, fabric finishing, and coating mills (44.9), apparel accessories and other apparel manufacturing (43.1), and animal slaughtering and processing (39.8). Industries with high rates of CTS should consider implementing intervention measures, including ergonomic evaluations and development of tools and instruments that require less repetition and force and that correct awkward postures.

Acute Illnesses and Injuries Related to Total Release Foggers - 10 States, 2007-2015.

Total release foggers (TRFs) (also known as "bug bombs") are pesticide products often used indoors to kill insects. After an earlier report found that TRFs pose a risk for acute illness (1), the Environmental Protection Agency required improved labels on TRFs manufactured after September 2012 (2). To examine the early impact of relabeling, the magnitude and characteristics of acute TRF-related illness were evaluated for the period 2007-2015. A total of 3,222 TRF-related illnesses were identified in 10 participating states, based on three data sources: Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR) programs, the California Department of Pesticide Regulation (CDPR) program, and poison control centers (PCCs) in Florida, Texas, and Washington. No statistically significant decline in the overall TRF-illness incidence rate was found. Failure to vacate treated premises during application was the most commonly reported cause of exposure. To reduce TRF-related illness, integrated pest management strategies (3) need to be adopted, as well as better communication about the hazards and proper uses of TRFs. Redesigning TRFs to prevent sudden, unexpected activation might also be useful.

Acute Occupational Pesticide-Related Illness and Injury -United States, 2007-2011.

CDC's National Institute for Occupational Safety and Health (NIOSH) collects data on acute pesticide-related illness and injury reported by 12 states (California, Florida, Iowa, Louisiana, Michigan, Nebraska, North Carolina, New Mexico, New York, Oregon, Texas, and Washington). This report summarizes the data on illnesses and injuries arising from occupational exposure to conventional pesticides from 2007 through 2011. This report is a part of the Summary of Notifiable Noninfectious Conditions and Disease Outbreaks - United States, which encompasses various surveillance years but is being published in 2016 (1). The Summary of Notifiable Noninfectious Conditions and Disease Outbreaks appears in the same volume of MMWR as the annual Summary of Notifiable Infectious Diseases (2). In a separate report, data on illnesses and injuries from nonoccupational exposure to pesticides during 2007-2011 are summarized (3).

Magnitude and characteristics of acute paraquat- and diquat-related illnesses in the US: 1998-2013.

BACKGROUND: Paraquat and diquat are among the most commonly used herbicides in the world. OBJECTIVES: Determine the magnitude, characteristics, and root causes for acute paraquat- and diquat-related illnesses in the US METHODS: Illnesses associated with paraquat or diquat exposure occurring from 1998 through 2011 were identified from the Sentinel Event Notification System for Occupational Risks (SENSOR)-Pesticides Program, the California Department of Pesticide Regulation (CDPR) Pesticide Illness Surveillance Program (PISP), and the Incident Data System (IDS). Cases identified by the National Poison Data System (NPDS) were reviewed for the years 1998-2003 and 2006-2013. RESULTS: A total of 300 paraquat- and 144 diquat-related acute illnesses were identified by SENSOR, PISP, and IDS. NPDS identified 693 paraquat- and 2128 diquat-related acute illnesses. In SENSOR/PISP/IDS, illnesses were commonly low severity (paraquat=41%; diquat=81%); however, SENSOR/PISP/IDS identified 24 deaths caused by paraquat and 5 deaths associated with diquat. Nineteen paraquat-related deaths were due to ingestion, seven of which were unintentional, often due to improper storage in beverage bottles. In SENSOR/PISP/IDS, paraquat and diquat-related acute illnesses were work-related in 68% (n=203) and 29% (n=42) of cases, respectively. When herbicide application site was known, the vast majority of acute paraquat-related illnesses (81%) arose from agricultural applications. Common root causes of illness were failure to use adequate personal protective equipment (PPE), application equipment failure, and spill/splash of herbicide. CONCLUSIONS: Although the magnitude of acute paraquat/diquat-related illnesses was relatively low, several fatalities were identified. Many illnesses could be prevented through stricter compliance with label requirements (e.g. ensuring proper herbicide storage and PPE use), and through enhanced training of certified applicators.

Using multiple data sets for public health tracking of work-related injuries and illnesses in California.

BACKGROUND: Research suggests the U.S. Bureau of Labor Statistics Survey of Occupational Injuries and Illnesses underestimates the magnitude of workplace injuries and illnesses. Enumerating workplace injuries and illnesses may be improved by utilizing multiple state-based data sources. METHODS: Using California-based datasets (workers' compensation claims, health care facility data, and physician reports), we enumerated unique cases of amputations and carpal tunnel syndrome (2007-2008), and evaluated the datasets for usefulness in occupational health tracking by performing record linkage across all datasets and calculating match rates between them. RESULTS: 6,862 amputation and 39,589 carpal tunnel syndrome (CTS) cases were identified. Match rates between the datasets ranged from 34.0% to 45.6% (amputations) and 3.0% to 43.5% (CTS). Enumerated amputation and CTS cases from state-based sources were about five and ten times greater than the BLS SOII estimates (1,390 and 3,720). CONCLUSIONS: Successful demonstration of this state level approach has broad implications for improving federal and state efforts to track and prevent work-related injuries and illnesses.

Characteristics and magnitude of acute pesticide-related illnesses and injuries associated with pyrethrin and pyrethroid exposures--11 states, 2000-2008.

BACKGROUND: Excluding disinfectants, pyrethrins and pyrethroids are the pesticides used most commonly in and around homes. Respiratory effects and paresthesia are among the concerns about pyrethrin/pyrethroid exposures. METHODS: Acute pesticide-related illness/injury cases were identified from the Sentinel Event Notification System for Occupational Risks-Pesticides Program and the California Department of Pesticide Regulation from 2000-2008. Characteristics and incidence rates were determined for acute pyrethrin/pyrethroid-related illness/injury cases. Logistic regression analyses were performed to determine odds of respiratory and dermal symptoms in persons with illness/injury following pyrethrin/pyrethroid exposure compared to persons with illness/injury following exposure to other pesticides. RESULTS: A total of 4,974 cases of acute pyrethrin/pyrethroid-related illness were identified. Incidence rates increased over time, reaching 8 cases/million population in 2008. The majority of cases were low severity (85%) and 34% were work-related. Respiratory effects were the most common symptoms reported (48%). Risk of acute respiratory effects were significantly elevated among persons exposed only to pyrethrins (adjusted odds ratio [aOR] 1.79; 95% confidence interval [95% CI]: 1.49-2.16), only to pyrethroids (aOR 1.99 95% CI: 1.77-2.24), to a mixture of pyrethroids (aOR 2.36; 95% CI: 1.99-2.81) or to a mixture containing both pyrethrins and pyrethroids (aOR 2.99; 95% CI: 2.33-3.84) compared to those with illness arising from exposure to other pesticides. The most common factors contributing to pyrethrin/pyrethroid-related illness included exposure from spills/splashes, improper storage, and failure to evacuate during pesticide application. CONCLUSIONS: The magnitude of acute pyrethrin/pyrethroid-related illness/injury is relatively low but is increasing. As such, additional measures to prevent them are needed.

Temporal assessment of disparities in California COVID-19 mortality by industry: a population-based retrospective cohort study.

PURPOSE: To assess changes in the COVID-19 mortality rate and disparities over variants or waves by industry. METHODS: We identified COVID-19 deaths that occurred between January 2020 and May 2022 among California workers aged 18-64 years using death certificates, and estimated Californians at risk using the Current Population Survey. The waves in deaths were wave 1: March-June 2020, wave 2: July-November 2020, wave 3/Epsilon and Alpha variants: December 2020-May 2021, wave 4/Delta variant: June 2021-January 2022, and wave 5/Omicron variant: February-May 2022. We used Poisson regression to generate wave-specific mortality rate ratios (MRR) and included an interaction term between industry and wave in different models to assess significance of the change in MRR. RESULTS: In all waves of the pandemic, healthcare, other services, manufacturing, transportation, and retail trade industries had higher mortality rates than the professional, scientific, and technical industry. The healthcare industry had the highest relative rate earlier in the pandemic, while other services, utilities, and accommodation and food services industries had substantial increases in MRR in later waves. CONCLUSIONS: Industries that consistently had disproportionate COVID-19 mortality may have benefitted from protections that consider workers' increased exposure and vulnerability to severe outcomes.

Gender differences in acute pesticide-related illnesses and injuries among farmworkers in the United States, 1998-2007.

BACKGROUND: Farmworkers have a high risk for acute pesticide-related illness and injury, and the rate among female farmworkers is approximately twice as high as that among males. Surveillance data were used to identify reasons for this gender difference. METHODS: We identified acute pesticide-related illness and injury cases among farmworkers from the Sentinel Event Notification System for Occupational Risks (SENSOR)-Pesticides Program and the California Department of Pesticide Regulation. Gender-specific associations with acute pesticide-related illness and injury were assessed using chi-square tests. National Agricultural Workers Survey data were also examined. RESULTS: The over-representation of females among farmworker illness and injury cases was confined to females who did not handle pesticides (non-handlers). Female non-handler farmworkers who were affected were more likely to be working on fruit and nut crops, to be exposed to off-target pesticide drift, and to be exposed to fungicides and fumigants compared to males. CONCLUSIONS: Although there is an increased risk for acute pesticide-related illness and injury among female farmworkers, the absolute number of farmworkers with acute pesticide-related illness and injury is far higher among males than females. Furthermore, farmworkers have little or no control over many of the identified contributing factors that led to illness and injury. Stringent enforcement of existing regulations and enhanced regulatory efforts to protect against off-target drift exposures may have the highest impact in reducing acute pesticide-related illness and injury among farmworkers.

Long-term Clinical Results of Carpal Tunnel Release Using Ultrasound Guidance.

BACKGROUND: The purpose of this study was to determine the long-term safety and efficacy of carpal tunnel release (CTR) using ultrasound guidance in a group of patients treated by a single physician. METHODS: The study group consisted of 76 consecutive CTRs performed on 47 patients between June 2017 and April 2019 for whom 1-year follow-up was available. All procedures were performed by the same operator using a single CTR technique. Outcomes included complications; Boston Carpal Tunnel Questionnaire symptom severity (BCTQ-SSS) and functional status (BCTQ-FSS) scores; Quick Disabilities of the Arm, Shoulder, and Hand (QDASH) scores; and a 5-point global satisfaction score (4 = satisfied, 5 = very satisfied). RESULTS: The 47 patients included 27 females and 20 males (ages 31-91 years). Twenty-five patients (50 hands) had simultaneous bilateral CTRs, 4 patients (8 hands) had staged bilateral CTRs, and 18 patients had unilateral CTRs. No complications occurred. Statistically and clinically significant reductions in BCTQ-SSS, BCTQ-FSS, and QDASH scores occurred by 1 to 2 weeks post-CTR and persisted at 1-year (mean 1-year changes vs. pre-CTR -2.11, -1.70, and -44.99, respectively; P < .001 for all). The mean global satisfaction score at 1-year was 4.63. CONCLUSIONS: CTR using ultrasound (US) guidance is a safe and effective procedure that produces statistically and clinically significant improvements within 1 to 2 weeks postprocedure that persist to 1 year. Furthermore, simultaneous bilateral CTRs using US guidance are feasible and may be advantageous for patients who are candidates for bilateral CTR.

Disparities in COVID-19 fatalities among working Californians.

BACKGROUND: Information on U.S. COVID-19 mortality rates by occupation is limited. We aimed to characterize 2020 COVID-19 fatalities among working Californians to inform preventive strategies. METHODS: We identified laboratory-confirmed COVID-19 fatalities with dates of death in 2020 by matching death certificates to the state's COVID-19 case registry. Working status for decedents aged 18-64 years was determined from state employment records, death certificates, and case registry data and classified as "confirmed working," "likely working," or "not working." We calculated age-adjusted overall and occupation-specific COVID-19 mortality rates using 2019 American Community Survey denominators. RESULTS: COVID-19 accounted for 8,050 (9.9%) of 81,468 fatalities among Californians 18-64 years old. Of these decedents, 2,486 (30.9%) were matched to state employment records and classified as "confirmed working." The remainder were classified as "likely working" (n = 4,121 [51.2%]) or "not working" (n = 1,443 [17.9%]) using death certificate and case registry data. Confirmed and likely working COVID-19 decedents were predominantly male (76.3%), Latino (68.7%), and foreign-born (59.6%), with high school or less education (67.9%); 7.8% were Black. The overall age-adjusted COVID-19 mortality rate was 30.0 per 100,000 workers (95% confidence interval [CI], 29.3-30.8). Workers in nine occupational groups had age-adjusted mortality rates higher than this overall rate, including those in farming (78.0; 95% CI, 68.7-88.2); material moving (77.8; 95% CI, 70.2-85.9); construction (62.4; 95% CI, 57.7-67.4); production (60.2; 95% CI, 55.7-65.0); and transportation (57.2; 95% CI, 52.2-62.5) occupations. While occupational differences in mortality were evident across demographic groups, mortality rates were three-fold higher for male compared with female workers and three- to seven-fold higher for Latino and Black workers compared with Asian and White workers. CONCLUSION: Californians in manual labor and in-person service occupations experienced disproportionate COVID-19 mortality, with the highest rates observed among male, Latino, and Black workers; these occupational group should be prioritized for prevention.

Variation in the vulnerability of mice expressing human superoxide dismutase 1 to prion-like seeding: a study of the influence of primary amino acid sequence.

Misfolded forms of superoxide dismutase 1 (SOD1) with mutations associated with familial amyotrophic lateral sclerosis (fALS) exhibit prion characteristics, including the ability to act as seeds to accelerate motor neuron disease in mouse models. A key feature of infectious prion seeding is that the efficiency of transmission is governed by the primary sequence of prion protein (PrP). Isologous seeding, where the sequence of the PrP in the seed matches that of the host, is generally much more efficient than when there is a sequence mis-match. Here, we used paradigms in which mutant SOD1 seeding homogenates were injected intraspinally in newborn mice or into the sciatic nerve of adult mice, to assess the influence of SOD1 primary sequence on seeding efficiency. We observed a spectrum of seeding efficiencies depending upon both the SOD1 expressed by mice injected with seeds and the origin of the seed preparations. Mice expressing WT human SOD1 or the disease variant G37R were resistant to isologous seeding. Mice expressing G93A SOD1 were also largely resistant to isologous seeding, with limited success in one line of mice that express at low levels. By contrast, mice expressing human G85R-SOD1 were highly susceptible to isologous seeding but resistant to heterologous seeding by homogenates from paralyzed mice over-expressing mouse SOD1-G86R. In other seeding experiments with G85R SOD1:YFP mice, we observed that homogenates from paralyzed animals expressing the H46R or G37R variants of human SOD1 were less effective than seeds prepared from mice expressing the human G93A variant. These sequence mis-match effects were less pronounced when we used purified recombinant SOD1 that had been fibrilized in vitro as the seeding preparation. Collectively, our findings demonstrate diversity in the abilities of ALS variants of SOD1 to initiate or sustain prion-like propagation of misfolded conformations that produce motor neuron disease.

Acute pesticide poisoning among agricultural workers in the United States, 1998-2005.

BACKGROUND: Approximately 75% of pesticide usage in the United States occurs in agriculture. As such, agricultural workers are at greater risk of pesticide exposure than non-agricultural workers. However, the magnitude, characteristics and trend of acute pesticide poisoning among agricultural workers are unknown. METHODS: We identified acute pesticide poisoning cases in agricultural workers between the ages of 15 and 64 years that occurred from 1998 to 2005. The California Department of Pesticide Regulation and the SENSOR-Pesticides program provided the cases. Acute occupational pesticide poisoning incidence rates (IR) for those employed in agriculture were calculated, as were incidence rate ratios (IRR) among agricultural workers relative to non-agricultural workers. RESULTS: Of the 3,271 cases included in the analysis, 2,334 (71%) were employed as farmworkers. The remaining cases were employed as processing/packing plant workers (12%), farmers (3%), and other miscellaneous agricultural workers (19%). The majority of cases had low severity illness (N = 2,848, 87%), while 402 (12%) were of medium severity and 20 (0.6%) were of high severity. One case was fatal. Rates of illness among various agricultural worker categories were highly variable but all, except farmers, showed risk for agricultural workers greater than risk for non-agricultural workers by an order of magnitude or more. Also, the rate among female agricultural workers was almost twofold higher compared to males. CONCLUSION: The findings from this study suggest that acute pesticide poisoning in the agricultural industry continues to be an important problem. These findings reinforce the need for heightened efforts to better protect farmworkers from pesticide exposure.

Plasma orexin A levels in recently menopausal women during and 3 years following use of hormone therapy.

OBJECTIVE: Alterations in sleep quality and metabolism during menopause are improved by menopausal hormone therapy (MHT). The mechanisms mediating these effects remain unclear. Orexin A (OxA) is a neuro-peptide that regulates sleep/wakefulness, food intake and metabolism. This study examined changes in plasma OxA levels during and after treatment in women from the Kronos Early Estrogen Prevention Study (KEEPS). METHODS: KEEPS randomized women within three years of menopause to: oral conjugated equine estrogen (o-CEE, 0.45mg/day), transdermal 17ß estradiol (t-E2, 50µg/day), or placebo pills and patches for four years. Plasma OxA levels were measured by enzyme immunoassays in fasting blood samples collected annually from KEEPS participants at Mayo Clinic during and three years after MHT. Changes in menopausal symptoms and plasma OxA levels were assessed for treatment differences. RESULTS: During treatment, OxA levels increased more in women randomized to o-CEE compared with the other groups. Women randomized to either form of MHT demonstrated smaller increases in BMI than those on placebo. Insomnia severity decreased similarly among treatment groups. However, neither changes in sleep nor changes in BMI correlated with changes in plasma OxA levels. Changes in waist circumference correlated positively with changes in plasma OxA levels three years after discontinuation of study treatments. CONCLUSIONS: Although OxA levels increased only in women randomized to o-CEE, these changes did not correlate with changes in sleep quality or BMI. The modest correlation of OxA levels with waist circumference once study treatments were discontinued suggests that OxA may be modulated through multiple intermediary pathways affected by metabolites of 17ß-estradiol. Clinical Trial Registration for KEEPS: NCT00154180.