Targeting CCNE1 amplified ovarian and endometrial cancers by combined inhibition of PKMYT1 and ATR.

Ovarian cancers (OVCAs) and endometrial cancers (EMCAs) with CCNE1-amplification are often resistant to standard of care treatment and represent an unmet clinical need. Previously, synthetic-lethal screening identified loss of the CDK1 regulator, PKMYT1, as synthetically lethal with CCNE1-amplification. We hypothesized that CCNE1-amplification associated replication stress will be more effectively targeted by combining the PKMYT1 inhibitor, lunresertib (RP-6306), with the ATR inhibitor, camonsertib (RP-3500/RG6526). Low dose combination RP-6306 with RP-3500 synergistically increased cytotoxicity more in CCNE1 amplified compared to non-amplified cells. Combination treatment produced durable antitumor activity and increased survival in CCNE1 amplified patient-derived and cell line-derived xenografts. Mechanistically, low doses of RP-6306 with RP-3500 increase CDK1 activation more so than monotherapy, triggering rapid and robust induction of premature mitosis, DNA damage and apoptosis in a CCNE1-dependent manner. These findings suggest that targeting CDK1 activity by combining RP-6306 with RP-3500 is a novel therapeutic approach to treat CCNE1-amplifed OVCAs and EMCAs.

Religion and Responsibility-Taking Among Offenders in Colombia and South Africa: A Qualitative Assessment of a Faith-Based Program in Prison.

This paper examines whether religion contributes to offenders taking responsibility for crimes. Specifically, we assessed whether participation in The Prisoner's Journey (TPJ), a bible study program, increased or decreased responsibility-taking. We also examined whether religious offenders that did not participate in TPJ were likely to take responsibility for their offenses. For this study, we conducted a quasi-experiment in two Colombian and five South African prisons from 2018 to 2019, collecting data from personal interviews with a total of 73 inmates-42 TPJ participants and 31 non-participants-before and after the program. Offenders frequently offered subtle accounts of responsibility that incorporated their own agency with other factors. Highly religious offenders were equally likely to take responsibility, and in some cases participation in TPJ heightened responsibility. In sum, this paper presents evidence that religious beliefs and practice are commensurate with responsibility-taking and desistance from crime.

Association Between Metabolic Syndrome and Endometrial Cancer Survival in a SEER-Medicare Linked Database.

BACKGROUND: Metabolic syndrome has previously been linked to increased risk of endometrial cancer. This study examines the association between metabolic syndrome and cancer-specific survival (CSS) in early stage and locoregionally advanced endometrial cancer. METHODS: The SEER-Medicare linked database was used to identify a cohort of patients with endometrial cancer between 1992 and 2011 who underwent hysterectomy. Patients with incomplete stage or grade information were excluded. Patients were stratified into early stage (stage I to II) or locoregionally advanced (stage III to IVa) disease. Metabolic syndrome status was determined through Medicare claims 1 year before diagnosis. The relationship between metabolic syndrome and CSS was evaluated using univariable and multivariable Cox proportional hazards regression analyses. RESULTS: A total of 10,090 patients with endometrial cancer were identified. The mean age was 75 and the majority (91.5%) were white. At diagnosis, 86.6% of patients were early stage and 13.4% were locoregionally advanced. Sixteen percent of patients had metabolic syndrome. On stage stratified multivariable analysis, race, income quartile, year of diagnosis, histopathology, and adjuvant treatment were associated with CSS in early stage disease. Presence of metabolic syndrome was associated with worse CSS in early stage disease (hazard ratio=1.28, 95% confidence interval: 1.09-1.53); this difference did not exist for locoregionally advanced disease (hazard ratio=1.18, 95% confidence interval: 0.93-1.49). CONCLUSIONS: In elderly early stage endometrial cancer patients, metabolic syndrome is associated with worse CSS. Control of metabolic syndrome through lifestyle and pharmacologic therapies may improve cancer prognosis in this population.

Is Expanded HIV Testing Associated with Earlier HIV Diagnosis? Results from an HIV Clinic in Guatemala City.

BACKGROUND: Most patients in Guatemala are diagnosed with advanced HIV disease. Patients that present late in the disease process may miss the morbidity and mortality benefits associated with early treatment and may unknowingly spread HIV to others. RESEARCH QUESTIONS: We examined trends in HIV detection and levels of immunosuppression at diagnosis from 2005 -2012 to determine if expanded HIV testing was associated with earlier detection of HIV. SETTING: This study was conducted at the Clínica Familiar Luis Ángel García (CFLAG), a major HIV center associated with one of Guatemala's two national hospitals. HIV testing expanded rapidly after 2007 due to grants from the Global Fund which allowed for routine prenatal testing. METHODS: This study examined existing hospital and clinic databases from to evaluate results from HIV tests performed, and baseline CD4 cells/mm(3) on all patients newly diagnosed with HIV infection from 2005 to 2012. RESULTS: We found a decline in the number of HIV positive tests over the study period despite an increase in the total number of tests performed. Sixty-two percent of HIV infected individuals had AIDS at diagnosis. We observed a decrease in median CD4 cells/mm(3) among the prenatal testees and no change in non-prenatal testees. DISCUSSION: Expanded HIV counseling and testing services in our clinic did not result in earlier HIV diagnosis.

Evaluación de la metastasectomía pulmonar para el tratamiento de los sarcomas ginecológicos / Reviewing pulmonary metastasectomy for treatment of gynecologic sarcomas

Los sarcomas ginecológicos con frecuencia auguran un mal pronóstico debido a la diseminación hematógena y por sus metástasis a distancia. Las opciones de tratamiento son limitadas y existen regímenes de quimioterapia que no resultan en una supervivencia prolongada. La resección quirúrgica de las metástasis pulmonares parece ser una medida terapéutica factible en pacientes con recurrencias aisladas, ya que ofrece remisiones prolongadas con una aceptable calidad de vida. En este trabajo se efectuó una revisión de la literatura sobre la supervivencia de las pacientes con sarcomas uterinos y se discute la importancia de los criterios clinicopatológicos que deberían guiar la selección de candidatas óptimas para esta intervención...

Measuring vortex charge with a triangular aperture.

A triangular aperture illuminated with a vortex beam creates a truncated lattice diffraction pattern that identifies the charge of the vortex. In this Letter, we demonstrate the measurement of vortex charge via this approach for vortex beams up to charge ±7. We also demonstrate the use of this technique for measuring femtosecond vortices and noninteger vortices, comparing these results with numerical modeling. It is shown that this technique is simple and reliable, but care must be taken when interpreting the results for the noninteger case.

Seroprevalence of HIV, hepatitis B, and syphilis among pregnant women at the general hospital, Guatemala City, 2005-2009.

BACKGROUND: sexually transmitted infection (STI) screening in pregnancy provides an excellent opportunity for secondary prevention. OBJECTIVE: to document the epidemiology of HIV, hepatitis B, and syphilis among pregnant women at a Guatemalan national hospital. RESULTS: from 2004 to 2009, 118 (0.76%) of 15 563 of women tested in the prenatal clinic had HIV infection, 29 (0.22%) of 13 028 women tested had hepatitis B virus infection, and 78 (0.60%) of 13 027 had a positive test for syphilis. From August 1, 2007 through December 31, 2009, 29 482 women were tested in the obstetrical emergency room. A total of 63 were HIV positive (0.21%), 48 had hepatitis B (0.16%), and 196 had syphilis (0.66%). Of the 9196 births between August 2007 and July of 2008, 33 (0.36%) were to HIV-infected mothers. CONCLUSION: these 3 STIs were uncommon in our population and did not increase in incidence during the study period. HIV maternal-to-child transmission (MTCT) prevention programs were feasible in our setting.

Does HIV VCT reduce risk behaviors? An observational study in Guatemala City.

OBJECTIVE: We examined the impact of HIV voluntary counseling and testing on self-reported behavioral risks three months after HIV testing. DESIGN: Cohort study comparing self-reported risk behaviors prior to and three months after HIV testing. SETTING: Clinica Familiar Luis Angel Garcia, an HIV specialty clinic located in a Guatemalan National Hospital. SUBJECTS, PARTICIPANTS: 144 people undergoing HIV testing were enrolled. 44 were HIV positive. 41 HIV positive and 49 HIV negative subjects returned for follow-up interviews. INTERVENTION: All subjects were tested and received voluntary counseling regarding HIV infection, transmission, prevention, and interpretation of HIV test results. MAIN OUTCOME MEASURE: The primary study outcome measure was change in self-reported risk behaviors three months after voluntary counseling and testing. RESULTS: Men were more likely than women to report a history of sexually transmitted diseases, more than 2 sexual partners, using alcohol with sex, and receiving money for sex; they were less likely to have a regular partner. 26% of men reported non-heterosexual orientation; no woman did. Alcohol was the primary drug of abuse in both men and women. At three month follow-up HIV positive subjects showed decreases in the average number of sexual partners, use of alcohol with sex, and episodes of unprotected sex. CONCLUSIONS: Voluntary counseling and testing resulted in changes in some self-reported risk behaviors, but only among HIV positive subjects. On nearly all measures men report riskier behavior than women. Alcohol is the most commonly used drug in this population and is often used with sex.

Experience of a pediatric HIV clinic in Guatemala City.

OBJECTIVES: To describe the clinical experience of a Guatemalan pediatric HIV clinic and referral center, and fill the gap in literature available on pediatric HIV in Guatemala, a country facing a growing HIV epidemic. METHODS: Analyses were performed on data available from the clinical databases maintained by the Clínica Familiar Luis Angel García within the Hospital General San Juan de Dios in Guatemala City, Guatemala. RESULTS: From January 1997-June 2006, a total of 536 children (individuals under 13 years of age) were registered at the clinic, 54% of them female. At the initial visit, 241 were known to be HIV infected, while 295 were known to have been exposed to HIV, but were of undetermined infection status. Of the 295 with undetermined status, serostatus was determined in 173, and 57 (33%) were HIV positive. The patients came from all 24 departments of Guatemala, but the majority (64%) was from Guatemala City. Most had perinatal exposure; three patients had been sexually exposed to HIV (all male); and the mode of infection could not be determined for six children. In the cohort of children whose infection status was initially undetermined, the provision of antiretroviral (ARV) medication (both pre- and neonatal), in addition to Cesarean section, was associated with an odds ratio of 0.06 for HIV infection (P < 0.001) when compared to children who had no interventions. Highly active antiretroviral therapy (HAART) was administered to 167 HIV-infected children. There were 44 known deaths in this cohort; no deaths occurred among the children who were not infected. CONCLUSIONS: Pediatric HIV/AIDS is present in all parts of Guatemala. Programs to prevent mother to child transmission and to provide appropriate treatment to families living with HIV/AIDS must be a public health priority.

Experience of a pediatric HIV clinic in Guatemala City / Experiencia de una clínica pediátrica para el VIH en la Ciudad de Guatemala

OBJECTIVES: To describe the clinical experience of a Guatemalan pediatric HIV clinic and referral center, and fill the gap in literature available on pediatric HIV in Guatemala, a country facing a growing HIV epidemic. METHODS: Analyses were performed on data available from the clinical databases maintained by the Clínica Familiar Luis ángel García within the Hospital General San Juan de Dios in Guatemala City, Guatemala. RESULTS: From January 1997-June 2006, a total of 536 children (individuals under 13 years of age) were registered at the clinic, 54 percent of them female. At the initial visit, 241 were known to be HIV infected, while 295 were known to have been exposed to HIV, but were of undetermined infection status. Of the 295 with undetermined status, serostatus was determined in 173, and 57 (33 percent) were HIV positive. The patients came from all 24 departments of Guate mala, but the majority (64 percent) was from Guatemala City. Most had perinatal exposure; three patients had been sexually exposed to HIV (all male); and the mode of infection could not be determined for six children. In the cohort of children whose infection status was initially undetermined, the provision of antiretroviral (ARV) medication (both pre- and neonatal), in addition to Cesarean section, was associated with an odds ratio of 0.06 for HIV infection (P < 0.001) when compared to children who had no interventions. Highly active antiretroviral therapy (HAART) was administered to 167 HIV-infected children. There were 44 known deaths in this cohort; no deaths occurred among the children who were not infected. CONCLUSIONS: Pediatric HIV/AIDS is present in all parts of Guatemala. Programs to prevent mother to child transmission and to provide appropriate treatment to families living with HIV/AIDS must be a public health priority.

OBJETIVOS: Describir la experiencia de una clínica y centro de referencia pediátrico para el VIH en Guatemala y llenar el vacío existente en la literatura científica sobre la infección pediátrica por el VIH en ese país, donde se enfrenta una creciente epidemia por el VIH. MÉTODOS: SE analizaron los datos disponibles en la base de datos clínicos de la Clínica Familiar Luis Ángel García del Hospital General San Juan de Dios, Ciudad de Guatemala, Guatemala. RESULTADOS: Entre enero de 1997 y junio de 2006 en la clínica se registraron 536 menores de 13 años; 54 por ciento de los cuales eran niñas. En la visita inicial se sabía que 241 estaban infectados por el VIH y que 295 habían estado expuestos a ese virus aunque su diagnóstico era indeterminado. De estos, se determinó el estatus serológico de 173, de los cuales 57 (33 por ciento) resultaron positivos al VIH. Los pacientes procedían de los 24 departamentos de Guatemala, pero la mayoría (64 por ciento) era de la Ciudad de Guatemala. La mayoría de los pacientes había estado expuestos al VIH por la vía perinatal; tres pacientes (todos varones), por la vía sexual y no se pudo determinar la vía de infección de seis niños. En la cohorte de niños con diagnóstico inicial indeterminado, el tratamiento antirretroviral (tanto pre como posnatal) junto con el nacimiento por cesárea se asociaron con una razón de posibilidades (odds ratio) de tener la infección por el VIH de 0,06 (P < 0,001) en comparación con los niños sin estas intervenciones. El tratamiento antirretroviral de gran actividad (HAART) se administró a 167 niños infectados por el VIH. Se registraron 44 muertes en esta cohorte, ninguna en los niños sin infección. CONCLUSIONES: La infección pediátrica por VIH/sida está presente en todos los departamentos de Guatemala. Los programas para evitar la transmisión de madre a hijo y brindar el tratamiento adecuado a las familias que viven con VIH/sida son una prioridad de salud pública.

Vaginal douching among Latinas: practices and meaning.

OBJECTIVES: Vaginal douching is widely practiced by American women, particularly among minority groups, and is associated with increased risk of pelvic and vaginal infections. This research sought to investigate vaginal hygiene practices and meaning associated with them among Latina women and adolescents. Study results would guide development of an intervention to decrease douching among Latinas. METHODS: In depth qualitative interviews conducted with English- and Spanish-speaking women aged 16-40, seeking care for any reason who reported douching within the last year (n = 34). Interviews were audiotaped, transcribed and analyzed using qualitative methods. One-third of interviews were conducted in Spanish. RESULTS: Two explanatory models for douching motives emerged: one stressed cosmetic benefits; the other, infection prevention and control. Most women reported douching to eliminate menstrual residue; a small number reported douching in context of sexual intercourse or vaginal symptoms. Many were unaware of associated health risks. Respondents typically learned about douching from female family members and friends. Male partners were described as having little to no involvement in the decision to douche. Women varied in their willingness to stop douching. Two-thirds reported receiving harm reduction messages about "overdouching". About half indicated previous discussion about douching with health care providers; some had reduced frequency in response to counseling. A number of previously unreported vaginal hygiene practices and products were described, including use of a range of traditional hygiene practices, and products imported from outside the US. CONCLUSIONS: Respondents expressed a range of commitment to douching. Counseling messages acknowledging benefits women perceive as well as health risks should be developed and delivered tailored to individual beliefs. Further research is needed to assess prevalence and safety of previously unreported practices.

Observations on genital morphology and anatomy of a hybrid male muriqui (genus Brachyteles).

The reproductive anatomy of the muriqui (genus Brachyteles) is poorly known. This paper describes the anatomy of the testis, penis and striated penile muscles in a young adult (5.25-year-old) captive-born muriqui which died at the Rio Primate Center. Two forms of muriqui occur in the Atlantic coastal forests of Brazil, and both are endangered. The form which is found north of 21 degrees 00' S latitude is classified as B. hypoxanthus by some authorities and is considered to be a species separate from B. arachnoides. The male specimen described here was a hybrid (the sire was B. arachnoides and the mother B. hypoxanthus). Hybridization was associated with absence of spermatozoa in the testis and with degeneration of the seminiferous epithelium. The structure of the prominent penis and striated penile muscles is discussed in relation to patterns of copulatory behavior and the likely occurrence of sperm competition in the muriqui. In addition, the occurrence of a baculum (os penis) is confirmed for this genus, and the first description of its morphology is provided.

The emergence of AIDS in Guatemala: inpatient experience at the Hospital General San Juan de Dios.

Little is known about the effect of human immunodeficiency virus (HIV) infection on the Central American healthcare system. We describe HIV-related admissions in a Guatemalan medical service. The study was conducted at Guatemala City's largest public hospital. Data were derived from standardized data collection sheets maintained by the HIV testing service and by HIV clinic physicians. Data were collected for 295 medicine admissions of 257 HIV-infected adults during an 18-month period in 1999 and 2000; 30% of the patients were women. Average age was 33 years. Only 12.5% of the patients had been diagnosed with HIV infection prior to 1999 and nearly all had symptomatic AIDS. 60.3% of the patients were diagnosed with HIV infection during their hospitalization. The most common discharge diagnoses were tuberculosis (13.9%), toxoplasmosis, diarrhoea, candida and other fungal infections, and meningitis. Mean length of stay for HIV-positive patients was 17 days. 23.7% of the patients died during their hospitalization; this was double the mortality of non-HIV patients. HIV-infected patients represented 5.8% of the total admissions of the general medical wards. In a country where HIV prevalence is thought to be less than 1%, AIDS is now responsible for over 5% of admissions to a large medical service at a cost of $500,000 per year. These findings underline the importance of HIV infection in Central America and demonstrate the utility of tracking hospital admission data as a method of surveillance.