Concurrent Outbreaks of Hepatitis A, Invasive Meningococcal Disease, and Mpox, Florida, USA, 2021-2022.

In 2022, concurrent outbreaks of hepatitis A, invasive meningococcal disease (IMD), and mpox were identified in Florida, USA, primarily among men who have sex with men. The hepatitis A outbreak (153 cases) was associated with hepatitis A virus genotype IA. The IMD outbreak (44 cases) was associated with Neisseria meningitidis serogroup C, sequence type 11, clonal complex 11. The mpox outbreak in Florida (2,845 cases) was part of a global epidemic. The hepatitis A and IMD outbreaks were concentrated in Central Florida and peaked during March--June, whereas mpox cases were more heavily concentrated in South Florida and had peak incidence in August. HIV infection was more common (52%) among mpox cases than among hepatitis A (21%) or IMD (34%) cases. Where feasible, vaccination against hepatitis A, meningococcal disease, and mpox should be encouraged among at-risk groups and offered along with program services that target those groups.

Outbreak of Listeriosis in South Africa Associated with Processed Meat.

BACKGROUND: An outbreak of listeriosis was identified in South Africa in 2017. The source was unknown. METHODS: We conducted epidemiologic, trace-back, and environmental investigations and used whole-genome sequencing to type Listeria monocytogenes isolates. A case was defined as laboratory-confirmed L. monocytogenes infection during the period from June 11, 2017, to April 7, 2018. RESULTS: A total of 937 cases were identified, of which 465 (50%) were associated with pregnancy; 406 of the pregnancy-associated cases (87%) occurred in neonates. Of the 937 cases, 229 (24%) occurred in patients 15 to 49 years of age (excluding those who were pregnant). Among the patients in whom human immunodeficiency virus (HIV) status was known, 38% of those with pregnancy-associated cases (77 of 204) and 46% of the remaining patients (97 of 211) were infected with HIV. Among 728 patients with a known outcome, 193 (27%) died. Clinical isolates from 609 patients were sequenced, and 567 (93%) were identified as sequence type 6 (ST6). In a case-control analysis, patients with ST6 infections were more likely to have eaten polony (a ready-to-eat processed meat) than those with non-ST6 infections (odds ratio, 8.55; 95% confidence interval, 1.66 to 43.35). Polony and environmental samples also yielded ST6 isolates, which, together with the isolates from the patients, belonged to the same core-genome multilocus sequence typing cluster with no more than 4 allelic differences; these findings showed that polony produced at a single facility was the outbreak source. A recall of ready-to-eat processed meat products from this facility was associated with a rapid decline in the incidence of L. monocytogenes ST6 infections. CONCLUSIONS: This investigation showed that in a middle-income country with a high prevalence of HIV infection, L. monocytogenes caused disproportionate illness among pregnant girls and women and HIV-infected persons. Whole-genome sequencing facilitated the detection of the outbreak and guided the trace-back investigations that led to the identification of the source.

Maternal and Perinatal Outcomes Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection During Pregnancy, Florida, 2020-2021: A Retrospective Cohort Study.

BACKGROUND: The objective was to estimate risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy and assess adverse maternal and perinatal outcomes. METHODS: We used a population-based, retrospective cohort of all pregnancies with a live birth or fetal death in Florida from 1 March 2020 to 30 April 2021. Coronavirus disease 2019 (COVID-19) case reports were matched to vital registries. Outcomes assessed were risk of infection in pregnancy, preterm birth, maternal or neonatal admission to an intensive care unit (ICU), perinatal or fetal death, and maternal death. Modified Poisson and multinomial logistic regression models were used to derive relative risk estimates. RESULTS: Of 234 492 women with a live birth or fetal death during the study period, 12 976 (5.5%) were identified with COVID-19 during pregnancy. Risk factors for COVID-19 in pregnancy included Hispanic ethnicity (relative risk [RR] = 1.89), Black race (RR = 1.34), being unmarried (RR = 1.04), and being overweight or obese pre-pregnancy (RR = 1.08-1.32). COVID-19 during pregnancy was associated with preterm birth (RR = 1.31), Cesarean delivery (RR = 1.04), and neonatal (RR = 1.17) and maternal (RR = 3.10) ICU admission; no association was found with increased risk of perinatal (RR = 0.72) or fetal death (RR = 0.86). Women infected during any trimester showed increased risk of preterm birth. Fourteen maternal deaths were identified among COVID-19 cases; of those who died, 12 were obese. The death rate per 10 000 was 22.09 among obese and 1.22 among non-obese gravida with COVID-19 during pregnancy (RR = 18.99, P = .001). CONCLUSIONS: Obesity is a risk factor for SARS-CoV-2 infection in pregnancy and for more severe COVID-19 illness among pregnant women. SARS-CoV-2 infection is associated with preterm birth.

South Africa field epidemiology training program: developing and building applied epidemiology capacity, 2007-2016.

In 2007, South Africa (SA) launched a field epidemiology training program (SAFETP) to enhance its capacity to prevent, detect, and respond to public health threats through training in field epidemiology. The SAFETP began as a collaboration between the SA National Department of Health (NDOH), National Institute for Communicable Diseases (NICD), and the University of Pretoria (UP), with technical and financial support from the U.S. Centers for Disease Control and Prevention (CDC). In 2010, the CDC in collaboration with the NICD, established a Global Disease Detection (GDD) Center in SA, and the SAFETP became a core activity of the GDD center. Similar to other FETPs globally, the SAFETP is a 2-year, competency-based, applied epidemiology training program, following an apprenticeship model of 'learn by doing'. SAFETP residents spend approximately 25% of the training in classroom-based didactic learning activities, and 75% in field activities to attain core competencies in epidemiology, biostatistics, outbreak investigation, scientific communication, surveillance evaluation, teaching others, and public health leadership. Residents earn a Master's in Public Health (MPH) degree from UP upon successfully completing a planned research study that serves as a mini-dissertation.Since 2007, SAFETP has enrolled an average of 10 residents each year and, in 2017, enrolled its 11th cohort. During the first 10 years of the program, 98 residents have been enrolled, 89% completed the 2-year program, and of these, 76 (87%) earned an MPH degree. Of those completing the program, 88% are employed in the public health sector, and work at NICD, NDOH, Provincial Health Departments, foreign health institutions, or non-governmental organizations. In the first 10 years of the program, the combined outputs of trainees included over 130 outbreak investigations, more than 150 abstracts presented at national and international scientific conferences, more than 80 surveillance system evaluations, and more than 45 manuscripts published in peer-reviewed scientific journals. The SAFETP is having an impact in building epidemiology capacity for public health in South Africa. Developing methods to directly link and measure the impact of the program is planned for the future.

Description of a Mass Poisoning in a Rural District in Mozambique: The First Documented Bongkrekic Acid Poisoning in Africa.

Background: On 9 January 2015, in a rural town in Mozambique, >230 persons became sick and 75 died of an illness linked to drinking pombe, a traditional alcoholic beverage. Methods: An investigation was conducted to identify case patients and determine the cause of the outbreak. A case patient was defined as any resident of Chitima who developed any new or unexplained neurologic, gastrointestinal, or cardiovascular symptom from 9 January at 6:00 am through 12 January at 11:59 pm. We conducted medical record reviews, healthcare worker and community surveys, anthropologic and toxicologic investigations of local medicinal plants and commercial pesticides, and laboratory testing of the suspect and control pombe. Results: We identified 234 case patients; 75 (32%) died and 159 recovered. Overall, 61% of case patients were female (n = 142), and ages ranged from 1 to 87 years (median, 30 years). Signs and symptoms included abdominal pain, diarrhea, vomiting, and generalized malaise. Death was preceded by psychomotor agitation and abnormal posturing. The median interval from pombe consumption to symptom onset was 16 hours. Toxic levels of bongkrekic acid (BA) were detected in the suspect pombe but not the control pombe. Burkholderia gladioli pathovar cocovenenans, the bacteria that produces BA, was detected in the flour used to make the pombe. Conclusions: We report for the first time an outbreak of a highly lethal illness linked to BA, a deadly food-borne toxin in Africa. Given that no previous outbreaks have been recognized outside Asia, our investigation suggests that BA might be an unrecognized cause of toxic outbreaks globally.

Transgenerational effects of di-(2-ethylhexyl) phthalate on testicular germ cell associations and spermatogonial stem cells in mice.

Recent evidence has linked human phthalate exposure to abnormal reproductive and hormonal effects. Phthalates are plasticizers that confer flexibility and transparency to plastics, but they readily contaminate the body and the environment. In this study, timed pregnant CD1 outbred mice were treated with di-(2-ethylhexyl) phthalate (DEHP) from Embryonic Day 7 (E7) to E14. The subsequent generation (F1) offspring were then bred to produce the F2, F3, and F4 offspring, without any further DEHP treatment. This exposure scheme disrupted testicular germ cell association and decreased sperm count and motility in F1 to F4 offspring. By spermatogonial transplantation techniques, the exposure scheme also disrupted spermatogonial stem cell (SSC) function of F3 offspring. The W/W(V) recipient testes transplanted with F3 offspring germ cells from the DEHP-treated group had a dramatically lower percentage of donor germ cell-derived spermatogenic recovery in seminiferous tubules when compared to the recipient testes transplanted with CD1 control germ cells. Further characterization showed that the major block of donor germ cell-derived spermatogenesis was before the appearance of undifferentiated spermatogonia. Interestingly, the testes transplanted with the F3 offspring germ cells from the DEHP-treated group, when regenerated, replicated testis morphology similar to that observed in the testes from the F1 to F3 offspring of the DEHP-treated group, suggesting that the germ cell disorganization phenotype originates from the stem cells of F3 offspring. In conclusion, embryonic exposure to DEHP was found to disrupt testicular germ cell organization and SSC function in a transgenerational manner.

Immunoprotective properties of primary Sertoli cells in mice: potential functional pathways that confer immune privilege.

Primary Sertoli cells isolated from mouse testes survive when transplanted across immunological barriers and protect cotransplanted allogeneic and xenogeneic cells from rejection in rodent models. In contrast, the mouse Sertoli cell line (MSC-1) lacks immunoprotective properties associated with primary Sertoli cells. In this study, enriched primary Sertoli cells or MSC-1 cells were transplanted as allografts into the renal subcapsular area of naive BALB/c mice, and their survival in graft sites was compared. While Sertoli cells were detected within the grafts with 100% graft survival throughout the 20-day study, MSC-1 cells were rejected between 11 and 14 days, with 0% graft survival at 20 days posttransplantation. Nonetheless, the mechanism for primary Sertoli cell survival and immunoprotection remains unresolved. To identify immune factors or functional pathways potentially responsible for immune privilege, gene expression profiles of enriched primary Sertoli cells were compared with those of MSC-1 cells. Microarray analysis identified 2369 genes in enriched primary Sertoli cells that were differentially expressed at ±4-fold or higher levels than in MSC-1 cells. Ontological analyses identified multiple immune pathways, which were used to generate a list of 340 immune-related genes. Three functions were identified in primary Sertoli cells as potentially important for establishing immune privilege: suppression of inflammation by specific cytokines and prostanoid molecules, slowing of leukocyte migration by controlled cell junctions and actin polymerization, and inhibition of complement activation and membrane-associated cell lysis. These results increase our understanding of testicular immune privilege and, in the long-term, could lead to improvements in transplantation success.

Cluster of serogroup W135 meningococci, southeastern Florida, 2008-2009.

Recently, 14 persons in southeastern Florida were identified with Neisseria meningitidis serogroup W135 invasive infections. All isolates tested had matching or near-matching pulsed-field gel electrophoresis patterns and belonged to the multilocus sequence type 11 clonal complex. The epidemiologic investigation suggested recent endemic transmission of this clonal complex in southeastern Florida.

Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States.

CONTEXT: Early data on pandemic 2009 influenza A(H1N1) suggest pregnant women are at increased risk of hospitalization and death. OBJECTIVE: To describe the severity of 2009 influenza A(H1N1) illness and the association with early antiviral treatment among pregnant women in the United States. DESIGN, SETTING, AND PATIENTS: Surveillance of 2009 influenza A(H1N1) in pregnant women reported to the Centers for Disease Control and Prevention (CDC) with symptom onset from April through December 2009. MAIN OUTCOME MEASURES: Severity of illness (hospitalizations, intensive care unit [ICU] admissions, and deaths) due to 2009 influenza A(H1N1) among pregnant women, stratified by timing of antiviral treatment and pregnancy trimester at symptom onset. RESULTS: We received reports on 788 pregnant women in the United States with 2009 influenza A(H1N1) with symptom onset from April through August 2009. Among those, 30 died (5% of all reported 2009 influenza A[H1N1] influenza deaths in this period). Among 509 hospitalized women, 115 (22.6%) were admitted to an ICU. Pregnant women with treatment more than 4 days after symptom onset were more likely to be admitted to an ICU (56.9% vs 9.4%; relative risk [RR], 6.0; 95% confidence interval [CI], 3.5-10.6) than those treated within 2 days after symptom onset. Only 1 death occurred in a patient who received treatment within 2 days of symptom onset. Updating these data with the CDC's continued surveillance of ICU admissions and deaths among pregnant women with symptom onset through December 31, 2009, identified an additional 165 women for a total of 280 women who were admitted to ICUs, 56 of whom died. Among the deaths, 4 occurred in the first trimester (7.1%), 15 in the second (26.8%), and 36 in the third (64.3%); CONCLUSIONS: Pregnant women had a disproportionately high risk of mortality due to 2009 influenza A(H1N1). Among pregnant women with 2009 influenza A(H1N1) influenza reported to the CDC, early antiviral treatment appeared to be associated with fewer admissions to an ICU and fewer deaths.

Potential functions of retinoic acid receptor A in Sertoli cells and germ cells during spermatogenesis.

Elucidation of the retinoid signaling circuitry in the testis is critical to understanding how male germ cells develop to spermatozoa. Retinoic acid receptor A protein (RARA) is an essential mediator of retinoid signaling in the testis, as shown by a sterility phenotype observed for retinoic acid receptor A gene (Rara) knockout male mice. The seminiferous tubules of Rara knockout mice showed varying degrees of germ-cell degeneration. A dramatic increase in apoptosis of early meiotic prophase spermatocytes was observed in these tubules compared to the wild-type tubules. Germ-cell loss was dependent on the stages of the spermatogenic cycle: germ-cell loss was negligible in stages I-V, but severe after stages VIII and IX of the spermatogenic cycle. Using spermatogonial transplantation, the individual function of RARA in Sertoli cells or germ cells was determined. The wild-type donor germ cells, transplanted into Rara knockout testes, colonized and proliferated in the RARA-deficient microenvironment. The donor-derived cells were mostly early meiotic prophase spermatocytes, with few more advanced germ cells detected. Conversely, when Rara-deficient germ cells were injected into the microenvironment that express RARA, establishment of donor-derived germ-cell colonies was rare, but remarkably, once colonized, Rara-deficient germ cells progressed normally through spermatogenesis. These results together suggest that RARA may function in Sertoli cells to promote the survival and development of early meiotic prophase spermatocytes, whereas RARA in germ cells functions to increase the proliferation and differentiation of spermatogonia, prior to meiotic prophase.

Clinical and Epidemiological Characterization of the First Recognized Outbreak of Dengue Virus-Type 2 in Mozambique, 2014.

Since the first reported epidemic of dengue in Pemba, the capital of Cabo Delgado province, in 1984-1985, no further cases have been reported in Mozambique. In March 2014, the Provincial Health Directorate of Cabo Delgado reported a suspected dengue outbreak in Pemba, associated with a recent increase in the frequency of patients with nonmalarial febrile illness. An investigation conducted between March and June detected a total of 193 clinically suspected dengue patients in Pemba and Nampula, the capital of neighboring Nampula Province. Dengue virus-type 2 (DENV-2) was detected by reverse transcriptase polymerase chain reaction in sera from three patients, and 97 others were classified as probable cases based on the presence of DENV nonstructural protein 1 antigen or anti-DENV immunoglobulin M antibody. Entomological investigations demonstrated the presence of Aedes aegypti mosquitos in both Pemba and Nampula cities.

PHSkb: a knowledgebase to support notifiable disease surveillance.

BACKGROUND: Notifiable disease surveillance in the United States is predominantly a passive process that is often limited by poor timeliness and low sensitivity. Interoperable tools are needed that interact more seamlessly with existing clinical and laboratory data to improve notifiable disease surveillance. DESCRIPTION: The Public Health Surveillance Knowledgebase (PHSkb) is a computer database designed to provide quick, easy access to domain knowledge regarding notifiable diseases and conditions in the United States. The database was developed using Protégé ontology and knowledgebase editing software. Data regarding the notifiable disease domain were collected via a comprehensive review of state health department websites and integrated with other information used to support the National Notifiable Diseases Surveillance System (NNDSS). Domain concepts were harmonized, wherever possible, to existing vocabulary standards. The knowledgebase can be used: 1) as the basis for a controlled vocabulary of reportable conditions needed for data aggregation in public health surveillance systems; 2) to provide queriable domain knowledge for public health surveillance partners; 3) to facilitate more automated case detection and surveillance decision support as a reusable component in an architecture for intelligent clinical, laboratory, and public health surveillance information systems. CONCLUSIONS: The PHSkb provides an extensible, interoperable system architecture component to support notifiable disease surveillance. Further development and testing of this resource is needed.

Transgenerational Effects of Di-(2-Ethylhexyl) Phthalate (DEHP) on Stress Hormones and Behavior.

Exposure to di-(2-ethylhexyl) phthalate (DEHP) has been linked to male reproductive abnormalities. Here, we assessed transgenerational actions of DEHP on several behaviors and stress responses. We used 2 doses of DEHP (150- and 200-mg/kg body weight) and a treatment regimen previously shown to produce transgenerational effects on male reproduction. Mice, 3 generations removed from DEHP exposure (F3), were tested for social behavior and anxiety on the elevated plus maze. We collected blood and pituitaries from undisturbed and restrained mice. Body weights, anogenital distances, and reproductive organ weights were collected at killing. In social interaction tests juvenile males from the DEHP lineage (200 mg/kg) displayed more digging and less self-grooming than did controls. Interestingly, 150-mg/kg lineage males, killed in early puberty, had smaller seminal vesicle weights than their controls. However, the 200-mg/kg males (killed on average 10 d later) did not show this effect. Females from a DEHP lineage had lower corticosterone concentrations than controls after restraint stress. We also found sex- and DEHP-specific mRNA expression changes in the pituitary in 2 of the 6 stress-related genes we measured. In particular, Gnas mRNA was elevated by the combination of DEHP lineage and stress. Thus, transgenerational effects of DEHP are noted in male behavior, and in females, DEHP had transgenerational effects on levels of corticosterone. Both of these results may be related to transgenerational modifications in the expression of several pituitary hormones involved in the hypothalamic-pituitary-adrenal axis.

Clinical features that discriminate inhalational anthrax from other acute respiratory illnesses.

Inhalational anthrax (IA) is a rapidly progressive disease that frequently results in sepsis and death, and prompt recognition is critical. To distinguish IA from other causes of acute respiratory illness, patients who had IA were compared with patients in an ambulatory clinic who had influenza-like illness (ILI) and with hospitalized patients who had community-acquired pneumonia (CAP) at the initial health care visit. Compared with patients who had ILI, patients who had IA were more likely to have tachycardia, high hematocrit, and low albumin and sodium levels and were less likely to have myalgias, headache, and nasal symptoms. Scoring systems were devised to compare IA with ILI or CAP on the basis of strength of association. For ILI, a score of > or =4 captured all 11 patients with IA and excluded 664 (96.1%) of 691 patients with ILI. Compared with patients who had CAP, patients with IA were more likely to have nausea or vomiting, tachycardia, high transaminase levels, low sodium levels, and normal white blood cell counts. For CAP, a score of > or =3 captured 9 (81.8%) of 11 patients with IA and excluded 528 (81.2%) of 650 patients with CAP. In conclusion, selected clinical features of patients with IA differ from those of patients with ILI and are more similar to those of patients with CAP.

Maternal and neonatal outcomes among pregnant women with 2009 pandemic influenza A(H1N1) illness in Florida, 2009-2010: a population-based cohort study.

INTRODUCTION: Pregnant women have been identified as a high risk group for severe illness with 2009 pandemic influenza A(H1N1) virus infection (pH1N1). Obesity has also been identified as a risk factor for severe illness, though this has not been thoroughly assessed among pregnant women. The objectives of this study were to provide risk estimates for adverse maternal and neonatal outcomes associated with pH1N1 illness during pregnancy and to assess the role of obesity in these outcomes. METHODS: We established a retrospective population-based cohort of all live births occurring in Florida during the first 15 months of the pandemic. Illness with pH1N1 during pregnancy was ascertained through record linkage with the Florida state notifiable disease surveillance database. Data from the birth record, including pre-pregnancy body mass index, were analyzed to assess risk of adverse outcomes associated with pH1N1 illness. RESULTS: A total of 194 women were identified through surveillance with pH1N1 illness during pregnancy. Children born to women with pH1N1 illness during pregnancy were at increased risk for low birth weight [OR (95%CI): 1.78 (1.11-2.860)], premature birth [2.21 (1.47-3.330)], and infant death [4.46 (1.80-11.00)], after adjusting for other factors. Women with pH1N1 illness during pregnancy were at increased risk for severe outcomes including admission to an intensive care unit. Obesity was an observed risk factor, both for the more severe pH1N1 illness detected through surveillance, and for severe maternal outcomes. CONCLUSIONS: Case-patients in this analysis likely represent the most severely ill subset of all women infected with pH1N1 during pregnancy, limiting the generalizability of these findings to more severely ill patients rather than influenza infection in general. Nevertheless, these results suggest that more severe pH1N1 illness during pregnancy is associated with adverse neonatal outcomes and that pregnant women should continue to be targeted for appropriate prophylaxis and early treatment.

Retinoic acid modulates the subcellular localization of small ubiquitin-related modifier-2/3 (SUMO-2/3) in the testis.

Covalent attachment of small ubiquitin-related modifier (SUMO) to target proteins is an important posttranslational mechanism controlling diverse cellular functions. Recently, hypo- or hyper-sumoylation by SUMO-2/3 was shown to play a crucial role in male reproduction. However, the regulation of SUMO-2/3 in the testis remains unknown. Here, we report that the subcellular localization of SUMO-2/3 changes during testicular development. SUMO-2/3 was mainly found localized in the nucleus of Sertoli cells and gonocytes early in testicular development, but the localization shifted to the cytoplasm in Sertoli and germ cells after meiotic initiation. This change in the subcellular localization was mimicked both in testes of postnatal day 10 (P10) rats injected with all-trans retinoic acid (ATRA) and in organ cultures of testes from P10 rats treated with ATRA. These results suggest that retinoic acid might have a role in controlling the subcellular localization of SUMO-2/3. Moreover, treatment of Sertoli cells with a retinoic acid receptor alpha (RARA)-specific agonist changed the subcellular localization of SUMO-2/3 from the nucleus to the cytoplasm. Furthermore, disruption of the retinoic acid receptor alpha (Rara) gene in the testis resulted in alteration of SUMO-2/3 subcellular localization, indicating that its protein RARA might have a role in the nuclear trafficking of SUMO-2/3. Because many SUMO target proteins are usually modified en masse after a biological stimulus, our results suggest that dysregulation of SUMO-2/3 subcellular localization could easily be a pleiotropic contributing factor that can cause a male sterility phenotype in Rara-null mice.

An outbreak of epidemic keratoconjunctivitis at an outpatient ophthalmology clinic.

Epidemic keratoconjunctivitis (EKC) is an acute eye infection caused by adenovirus. We investigated an outbreak of EKC at an outpatient ophthalmology practice in the context of a suspected community wide increase in EKC activity. A site visit was made to the facility reporting the outbreak. A line list was created of patients clinically diagnosed with EKC at the practice during the previous 5 months. A questionnaire was faxed to all other licensed ophthalmologists in the county regarding recent EKC activity in their facility. Descriptive data analyses were conducted. The outbreak facility reported 37 patients clinically diagnosed with EKC during the previous 5 months. In addition, the single ophthalmologist at the practice also had symptoms compatible with EKC during the outbreak period. Specimens were collected on 4 patients and all were positive for adenovirus serotype 8. Forty percent of ophthalmologists surveyed in the county saw at least one EKC patient in the previous 3 months, and 20% reported a perceived increase in EKC activity in recent months over normal seasonal patterns. The outbreak at the facility likely began as part of a widespread community increase in EKC that may have been amplified at the facility through nosocomial transmission. Medical providers experiencing increases in EKC activity above seasonally expected norms should contact their public health department for assistance with etiologic diagnoses and outbreak control.

Temporal profiling of rat transcriptomes in retinol-replenished vitamin A-deficient testis.

At least in mammals, retinoic acid is a pivotal factor in maintaining the functionality of the testis, in particular, for the progression of germ cells from mitosis to meiosis. Removal of dietary vitamin A or a targeted deletion of retinoic acid receptor alpha gene (Rara), the receptor for retinoic acid, in mice, led to testicular degeneration by a dramatic loss of germ cells and a loss of control of the spermatogenic cycle. The germ cells that remained in the vitamin A deficient (VAD) rat testis were spermatogonia and a few preleptotene spermatocytes. Spermatogenesis can be reinitiated by injection of VAD rats with retinol, the metabolic precursor of retinoic acid, but to date, the functions of retinoic acid in the testis remain elusive. We have applied DNA microarray technology to investigate the time-dependent transcriptome changes that occur 4 to 24 h after retinol replenishment in the VAD rat testis. The retinol-regulated gene expression occurred both in germ cells and Sertoli cells. Bioinformatic analyses revealed time-dependent clusters of genes and canonical pathways that may have critical functions for proper progression through spermatogenesis. In particular, gene clusters that emerged dealt with: (1) cholesterol and oxysterol homeostasis, * (2) the regulation of steroidogenesis, (3) glycerophospholipid metabolism, (4) the regulation of acute inflammation, (5) the regulation of the cell cycle including ubiquitin-mediated degradation of cell cycle proteins and control of centrosome and genome integrity, and (6) the control of membrane scaffolding proteins that can integrate multiple small GTPase signals within a cell. These results provide insights into the potential role of retinoic acid in the testis.

Retinoic acid regulation of eye and testis-specific transcripts within a complex locus.

We previously used a yeast-based enhancer trap to identify a strong, retinoic acid response element (RARE). We have now characterized testis and eye transcripts that are adjacent to this regulatory element. Bioinformatics analysis of expressed sequence tag (EST) clones and RNase protection, reverse transcription-PCR, and Northern blot assays indicate that these two RNAs are transcribed from the same locus on opposite template strands. This positions the RARE upstream of the testis transcript and downstream of the eye transcript. Additionally, these two RNAs are embedded within the third intron of the 329kbp gene that encodes the Zinc Finger and BTB domain containing 7C protein (Zbtb7C). We present evidence indicating that the testis transcript is expressed primarily in spermatocytes and/or early round spermatids. Furthermore, our analyses of transcript levels in eyes and testes isolated from vitamin A deficient mice or from mice with defects in retinoid storage or signaling indicate that retinoids are required for expression in vivo.

Completeness of notifiable infectious disease reporting in the United States: an analytical literature review.

Despite state and local laws requiring medical providers to report notifiable infectious diseases to public health authorities, reporting is believed to be incomplete. Through means of an analytical literature review, the authors synthesize current knowledge on the completeness of disease reporting and identify factors associated with reporting completeness. The review was limited to published studies, conducted in the United States between 1970 and 1999, that quantitatively assessed infectious disease reporting completeness. Thirty-three studies met the inclusion criteria. Reporting completeness, expressed between 0% and 100%, was treated as the dependent outcome variable in statistical analysis; disease, study location, time period, study design, and study size were treated as independent variables. Fifty-six distinct measures of reporting completeness were identified for 21 diseases. Reporting completeness varied from 9% to 99% and was most strongly associated with the disease being reported. The mean reporting completeness for acquired immunodeficiency syndrome, sexually transmitted diseases, and tuberculosis as a group was significantly higher (79%) than for all other diseases combined (49%) (p < 0.01).