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1.
Blood ; 142(26): 2305-2314, 2023 12 28.
Article in English | MEDLINE | ID: mdl-37883798

ABSTRACT

ABSTRACT: Platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies and anti-PF4 antibodies cause heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombocytopenia and thrombosis (VITT), respectively. Diagnostic and treatment considerations differ somewhat between HIT and VITT. We identified patients with thrombocytopenia and thrombosis without proximate heparin exposure or adenovirus-based vaccination who tested strongly positive by PF4/polyanion enzyme-immunoassays and negative/weakly positive by heparin-induced platelet activation (HIPA) test but strongly positive by PF4-induced platelet activation (PIPA) test (ie, VITT-like profile). We tested these patients by a standard chemiluminescence assay that detects anti-PF4/heparin antibodies found in HIT (HemosIL AcuStar HIT-IgG(PF4-H)) as well as a novel chemiluminescence assay for anti-PF4 antibodies found in VITT. Representative control sera included an exploratory anti-PF4 antibody-positive but HIPA-negative/weak cohort obtained before 2020 (n = 188). We identified 9 patients with a clinical-pathological profile of a VITT-like disorder in the absence of proximate heparin or vaccination, with a high frequency of stroke (arterial, n = 3; cerebral venous sinus thrombosis, n = 4), thrombocytopenia (median platelet count nadir, 49 × 109/L), and hypercoagulability (greatly elevated D-dimer levels). VITT-like serological features included strong reactivity by PIPA (aggregation <10 minutes in 9/9 sera) and positive testing in the novel anti-PF4 chemiluminescence assay (3/9 also tested positive in the anti-PF4/heparin chemiluminescence assay). Our exploratory cohort identified 13 additional patient sera obtained before 2020 with VITT-like anti-PF4 antibodies. Platelet-activating VITT-like anti-PF4 antibodies should be considered in patients with thrombocytopenia, thrombosis, and very high D-dimer levels, even without a proximate exposure to heparin or adenovirus vector vaccines.


Subject(s)
Antibodies , Thrombocytopenia , Thrombosis , Thrombocytopenia/diagnosis , Thrombocytopenia/pathology , Heparin , Vaccination , Humans , Platelet Factor 4/metabolism , Antibodies/analysis , Male , Female , Child, Preschool , Child , Adult , Thrombosis/diagnosis , Thrombosis/pathology
2.
J Gerontol Nurs ; 48(11): 37-43, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36286503

ABSTRACT

Physical activity performed with music activates important brain areas associated with cognition, emotions, and motor skills. Limited information is available on the feasibility and acceptability of physical activity and music interventions. The current study aimed to (a) determine the feasibility of a physical training intervention with music in older women, and (b) describe the differences between pretest and posttest variables (i.e., cognitive state, immediate memory, executive function, gait parameters [cadence and gait speed], muscle strength, flexibility, and symptoms of depression). Results suggest that the intervention with physical training and music was feasible, given the high acceptability and retention rates, high level of attendance at the sessions, and absence of adverse events. Significant improvements were observed in immediate memory (p ≤ 0.01), executive function (p ≤ 0.05), cadence (p ≤ 0.01), leg strength (p ≤ 0.01), right arm strength (p ≤ 0.01), left arm strength (p ≤ 0.05), symptoms of depression (p ≤ 0.01), and left lower body flexibility (p ≤ 0.05). Therefore, a randomized clinical trial with a larger sample could confirm the effects of this intervention on memory, executive function, cadence, leg strength, arm strength, symptoms of depression, and left lower body flexibility. [Journal of Gerontological Nursing, 48(11), 37-43.].


Subject(s)
Independent Living , Music , Humans , Female , Aged , Feasibility Studies , Gait/physiology , Exercise
4.
AIDS Care ; 28(2): 191-6, 2016.
Article in English | MEDLINE | ID: mdl-26301864

ABSTRACT

INTRODUCTION: The purpose of the study was to evaluate the effect of an Internet-based intervention to reduce sexual risk behaviors and increase resilience to sexual risk behaviors among Mexican adolescents, a key HIV/AIDS risk group. METHODOLOGY: The study had a quasi-experimental design with single-stage cluster sampling. Participants ages 14-17 were stratified by gender and randomly assigned to either receive intervention "Connect" (which included face-to-face and Internet-based sessions designed to reduce sexual risk behaviors and increase resilience to sexual risk) or control (a general educational video on reducing health risks). A total of 9 survey instruments were administered online through SurveyMonkey pre- and post-intervention to assess changes in sexual risk and protective factors as well as two outcomes of interest: risky sexual behaviors and resilience. Pearson correlation assessed instrument reliability while multivariable linear regression models assessed two study hypotheses: (1) the effect of the intervention on sexual behavior and resilience is mediated by adolescent age, gender, and sexual experience and (2) risk and protective factors are mediators between the intervention and sexual behavior. RESULTS: The sample was composed of 193 adolescents between 14 and 17 years old (n = 96 in the control group and n = 97 in the experimental group). Survey instruments were reliable. Age was associated with pre-to-post test changes in sexual resilience (ß = -6.10, p = .019), which partially mediated the effect of the intervention on sexual resilience (ß = 5.70, p = .034). Social support was associated with pre-to-post test changes in risky sexual behavior (ß = -0.17, p = .039). CONCLUSION: Intervention "Connect" was independently associated with improved self-reported resilience to risky sexual behaviors, though not with a reduction in those behaviors in multivariate analyses. This is the first Internet-based intervention designed to reduce HIV/AIDS sexual risk among Mexican adolescents.


Subject(s)
Acquired Immunodeficiency Syndrome/prevention & control , HIV Infections/prevention & control , Internet , Sexual Behavior , Adolescent , Adolescent Behavior , Female , Humans , Male , Reproducibility of Results , Risk-Taking , Unsafe Sex
5.
Issues Ment Health Nurs ; 36(4): 258-65, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25988376

ABSTRACT

Sexually transmitted infections including human immunodeficiency virus are international public health concerns. Heterosexual women who are in steady relationships have been described as a particularly vulnerable population at risk for sexually transmitted infections acquired from their male partners. In this pilot study, we describe associations identified via cross-sectional survey among demographic variables, attachment style, and condom use in Mexican heterosexual women (ages 20-44 years, n  =  50) who self-reported current steady partner relationships. Descriptive, bivariate, and correlation analyses were conducted. Secure attachment and condom use were positively correlated with education level. Limited sexual risk prevention knowledge and contraception use, low risk perception within male partner relationships and misconception about proper condom use were identified as sources of elevated risk for sexually transmitted infections via male partners. Implications of findings include sexual health intervention modification to include dialogue concerning the context of steady relationship and sexual risk among Mexican heterosexual women.


Subject(s)
Heterosexuality/ethnology , Heterosexuality/psychology , Safe Sex/ethnology , Safe Sex/psychology , Sexually Transmitted Diseases/prevention & control , Adult , Condoms , Contraception Behavior/ethnology , Contraception Behavior/psychology , Cross-Sectional Studies , Educational Status , Female , Humans , Marital Status , Mexico , Pilot Projects , Self Report , Young Adult
6.
Invest New Drugs ; 32(5): 825-37, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24919854

ABSTRACT

The G1 restriction point is critical for regulating the cell cycle and is controlled by the Rb pathway (CDK4/6-cyclin D1-Rb-p16/ink4a). This pathway is important because of its inactivation in a majority of human tumors. Transition through the restriction point requires phosphorylation of retinoblastoma protein (Rb) by CDK4/6, which are highly validated cancer drug targets. We present the identification and characterization of a potent CDK4/6 inhibitor, LY2835219. LY2835219 inhibits CDK4 and CDK6 with low nanomolar potency, inhibits Rb phosphorylation resulting in a G1 arrest and inhibition of proliferation, and its activity is specific for Rb-proficient cells. In vivo target inhibition studies show LY2835219 is a potent inhibitor of Rb phosphorylation, induces a complete cell cycle arrest and suppresses expression of several Rb-E2F-regulated proteins 24 hours after a single dose. Oral administration of LY2835219 inhibits tumor growth in human tumor xenografts representing different histologies in tumor-bearing mice. LY2835219 is effective and well tolerated when administered up to 56 days in immunodeficient mice without significant loss of body weight or tumor outgrowth. In calu-6 xenografts, LY2835219 in combination with gemcitabine enhanced in vivo antitumor activity without a G1 cell cycle arrest, but was associated with a reduction of ribonucleotide reductase expression. These results suggest LY2835219 may be used alone or in combination with standard-of-care cytotoxic therapy. In summary, we have identified a potent, orally active small-molecule inhibitor of CDK4/6 that is active in xenograft tumors. LY2835219 is currently in clinical development.


Subject(s)
Aminopyridines/pharmacology , Antineoplastic Agents/pharmacology , Benzimidazoles/pharmacology , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Cyclin-Dependent Kinase 6/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacology , Aminopyridines/therapeutic use , Animals , Antineoplastic Agents/therapeutic use , Benzimidazoles/therapeutic use , Cell Line, Tumor , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Drug Therapy, Combination , Female , G1 Phase Cell Cycle Checkpoints/drug effects , Humans , Mice , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Phosphorylation/drug effects , Protein Kinase Inhibitors/therapeutic use , Retinoblastoma Protein/antagonists & inhibitors , Retinoblastoma Protein/metabolism , Tumor Burden/drug effects , Xenograft Model Antitumor Assays , Gemcitabine
7.
Article in English | MEDLINE | ID: mdl-39145669

ABSTRACT

ABSTRACT: The return of a migrant partner can negatively impact the sexual health of women who stayed in their communities. Understanding their sexual health needs is crucial for developing targeted interventions and support systems. Our study used a critical ethnographic approach in Agua Dulce, a rural community in Mexico, involving 50 key informants: women who stayed behind (n = 20), returnees (n = 12), community leaders (n = 12), and health care professionals (n = 6). We used participant observation, policy analysis, and interviews, using purposeful and snowball sampling methods. A gender-based thematic analysis revealed economic hardships and early separations affect the sexual well-being of women who stay behind. Infidelity, discovered through social media or calls, causes emotional distress and family disruptions. Male migrants spend an average of 8.85 years abroad, leading to fears of risky sexual behaviors. Our study highlights the urgent need for specialized support centers and comprehensive health interventions.

8.
Rev Invest Clin ; 65(4): 291-9, 2013.
Article in English | MEDLINE | ID: mdl-24304729

ABSTRACT

BACKGROUND: Nutritional status and nutritional care have long been ignored among HIV/AIDS patients. Furthermore, in Mexico there is no information on potential factors favoring weight increase in such population. OBJECTIVE: To assess the association between the time period since diagnosis, demographics and BMI in different categories of patients with HIV/AIDS in Monterrey, Mexico. In addition, to provide information on overweight/obesity prevalence and nutritional care referral. MATERIAL AND METHODS: This was a cross-sectional study of HIV/AIDS positive patients receiving outpatient secondary care (n = 231). Nutritional care referral, time period since diagnosis and demographic data were obtained by interview. A standardized and registered dietitian collected anthropometrics measures. Binary multiple logistic regression was used to evaluate the association between increasing BMI categories and variables of interest. RESULTS: Mean patient age was 40.6 ± 11.2 years, 87% were male, 79.2% were economically active, 65% were single and 60% had less than a college education. The average time since diagnosis was 6.5 ± 5.4 years. Overweight and obesity prevalence were 35.8% and 12.5%, respectively. Only 18% of patients had ever been referred for nutritional care. The time period since diagnosis, the sum of skinfold measurements and the waist-to-hip ratio, were significantly predictive of the BMI category (normal/underweight vs. overweight/obese), when controlling for nutritional care referral and daily carbohydrate intake; age and marital status were not associated with BMI category. CONCLUSIONS: Identification of predisposing factors to overweight/obesity among HIV/AIDS patients constitutes a significant step for providing nutritional care, of the same importance as the load or CD4+ count, especially nowadays, with more common increased survival rates and consequently, longer lives with the disease.


Subject(s)
HIV Infections/diet therapy , Nutrition Therapy , Acquired Immunodeficiency Syndrome/complications , Acquired Immunodeficiency Syndrome/diagnosis , Acquired Immunodeficiency Syndrome/diet therapy , Adult , Body Mass Index , Cross-Sectional Studies , Female , HIV Infections/complications , HIV Infections/diagnosis , Humans , Male , Obesity/complications , Obesity/epidemiology , Overweight/complications , Overweight/epidemiology , Prevalence , Time Factors
9.
Eur J Pediatr Surg ; 33(1): 61-67, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36257335

ABSTRACT

INTRODUCTION: The addition of ultrasound-guided percutaneous cryoanalgesia (PCr) for pain management after pectus excavatum (PE) surgery offers a new and advantageous approach. Our aim is to describe our experience with PCr applied on the same day, 24 hours, and 48 hours prior to PE surgery. MATERIAL AND METHODS: Prospective pilot study in patients undergoing ultrasound-guided PCr (2019-2022) was divided into three groups: PCr on the same day of surgery (PCrSD), PCr 24 hours before (PCr24), and PCr 48 hours before (PCr48). We describe the application of technique and data obtained by comparing the three groups. RESULTS: We present 42 patients (25 PCrSD, 11 PCr24, 6 PCr48). PCr24 had a shorter procedure duration than PCrSD (65.8 vs. 91.2 minute; p = 0.048). Related to analgesia, PCr24 and PCr48 showed lower opioid consumption than PCrSD in PCA volume (48.5 and 49.6 vs. 75.1 mL; p = 0.015) and PCA time (23.3 and 23.8 vs. 34.3 hours; p = 0.01). Degree of pain (VAS scale) on the day of surgery and on the second postoperative day was lower in PCr24 and PCr48 than in PCrSD (4 and 2 vs. 5; p = 0.012; 0 and 1 vs. 2; p = 0.01, respectively) as well as shorter hospital stay (3 and 3.5 vs. 5 days; p = 0.021). In addition, PCr24 showed lower opioid consumption and hospital stay than PCr48 (p > 0.05). The greatest savings in hospital costs were obtained in the PCr24 group. CONCLUSION: PCr48 and PCr24 prior to PE surgery offers lower opioid consumption, less pain and shorter hospital stay than PCrSD. PCr24 is comparable to PCr48, but seems to show advantages and simpler logistics for the patient and the hospital.


Subject(s)
Analgesics, Opioid , Funnel Chest , Humans , Analgesics, Opioid/therapeutic use , Prospective Studies , Funnel Chest/complications , Funnel Chest/surgery , Pilot Projects , Pain, Postoperative/etiology , Pain, Postoperative/therapy , Ultrasonography, Interventional , Retrospective Studies
10.
Int J Soc Psychiatry ; 69(5): 1260-1267, 2023 08.
Article in English | MEDLINE | ID: mdl-36825658

ABSTRACT

BACKGROUND: Different stages of a physician's career may be associated with different types of mental health impairment. AIMS: This study aimed to compare symptoms of anxiety, depression, and stress and their associated factors among medical students, medical residents, and physicians. METHODS: A cross-sectional study was conducted. Data collection included sociodemographic data, religiosity (Duke University Religion Index), and mental health (21-item Depression, Anxiety and Stress Scale - DASS-21) data. The comparison between the groups was performed using ANOVA, and the associated factors were evaluated via linear regression models. RESULTS: The sample consisted of 1,417 participants: 778 medical students, 190 medical residents, and 468 established physicians. Medical students had significantly higher depression, anxiety, and stress scores as compared to medical residents and established physicians. However, regarding DASS 21 scores, no significant differences were found between established physicians and medical residents. The factors associated with mental health in the different groups showed that being married and male were associated with better mental health among physicians and medical residents, while the factors of male gender, being in later years of the course, and lower religious attendance were associated with better mental health in students. CONCLUSION: Medical students had worse mental health outcomes when compared to residents and established physicians. Interventions are needed to minimize suffering during medical education and career.


Subject(s)
Mental Health , Students, Medical , Humans , Male , Students, Medical/psychology , Depression/psychology , Cross-Sectional Studies , Anxiety/psychology , Stress, Psychological/epidemiology , Stress, Psychological/psychology
11.
Children (Basel) ; 10(6)2023 May 24.
Article in English | MEDLINE | ID: mdl-37371153

ABSTRACT

The goal of this research was to determine the personal, interpersonal, and sociocultural predictors of condom use among rural Indigenous adolescents. Predictor variables were selected from Bandura's Social Cognitive Theory and Leininger's Transcultural Theory. The sample consisted of 419 Nahuas adolescents randomly selected from the total number of neighborhood blocks in a rural community in Puebla, Mexico. The instruments had acceptable psychometric characteristics (Cronbach alpha and validity scores). Multiple linear regression models were used. Results: 56.8% of participants were female, and 50.40% were students. Mean age was M = 17.5 (SD = 0.97), and the majority (63%) identified as Catholic. Age at menarche/first ejaculation (ß = -1.2, p = 0.038), attitude toward condom use (ß = 0.13, p < 0.001), ethnic identity (ß = 0.21, p < 0.001), and ability to negotiate condom use (ß = 0.13, p = 0.003) predicted (R2 = 22.3) condom use. This study provided a basis for integration of the cultural values of Indigenous adolescents within interventions for sexual health promotion.

12.
Rev Med Inst Mex Seguro Soc ; 50(2): 147-55, 2012.
Article in Spanish | MEDLINE | ID: mdl-22882982

ABSTRACT

OBJECTIVE: to identify neurodevelopmental sequelae in one year old infants with perinatal encephalopathy utilizing the neurobehavioral scale named Vanedela. METHODS: a cohort of 75 newborns with perinatal encephalopathy was assessed with a neurobehavioral follow-up scale at age of 1, 4, 8 and 12 months. A distinction was made between functional, structural and combined encephalopathy. Two groups of neurodevelopmental outcome at one year were identified: with or without sequelae. Nonparametric statistics was used. RESULTS: infants with functional encephalopathy had the best scores, followed by those with structural encephalopathy, while infants with a combined encephalopathy had the lowest scores. At one year of age, the group with neurobehavioral sequelae exhibited the lowest scores and retarded growth. At the same age, the group with functional encephalopathy exhibited no neurobehavioral sequelae, and reached better scores and growth. CONCLUSIONS: the neurobehavioral follow-up scale is able to identify the neurodevelopmental sequelae at the age of one year in infants with perinatal encephalopathy. The application of Vanedela in the clinical field requires of little time, its results are trustworthy and very useful for the neurobehavioral follow-up assessment.


Subject(s)
Brain Diseases/complications , Mental Disorders/etiology , Nervous System Diseases/etiology , Female , Humans , Infant , Male
13.
Materials (Basel) ; 15(8)2022 Apr 08.
Article in English | MEDLINE | ID: mdl-35454441

ABSTRACT

Three-dimensional printed concrete (3DPC) is a relatively recent technology that may be very important in changing the traditional construction industry. The principal advantages of its use are more rapid construction, lower production costs, and less residues, among others. The choice of raw materials to obtain adequate behavior is more critical than for traditional concrete. In the present paper a mixture of cement, silica fume, superplasticizer, setting accelerator, filler materials, and aggregates was studied to obtain a 3DPC with high resistance at short curing times. When the optimal mixture was found, metallic fibers were introduced to enhance the mechanical properties. The fresh and hard properties of the concrete were analyzed, measuring the setting time, workability, and flexural and compressive strength. The results obtained demonstrated that the incorporation of fibers (2% in volume) enhanced the flexural and compressive strength by around 163 and 142%, respectively, compared with the mixture without fibers, at 9 h of curing. At 28 days of curing, the improvement was 79.2 and 34.7% for flexural and compressive strength, respectively.

14.
Rev Int Androl ; 20(2): 80-85, 2022.
Article in Spanish | MEDLINE | ID: mdl-35078727

ABSTRACT

INTRODUCTION: In 2019, 9,828 new cases of HIV and 5,825 of AIDS were detected in Mexico, the migrant population is considered highly vulnerable, which is presumed to be due to unfavorable conditions in their transit through the country, an important variable in the context of sexual health is the perception that they may have about being or not at risk. A study of perception of contracting HIV can have important implications for health. OBJECTIVE: To determine the association between the perception of risk for HIV and safe sex in migrants from the northern border of Mexico. METHODS: The design was predictive correlational and cross-sectional, sample of 302 migrants from two border cities of Tamaulipas, systematic random probability sampling. RESULTS: It was found that about 90% were men with a mean age of (M = 33,25, SD = 9,62) years, in general, migrants have a low perception of risk for HIV and this was correlated with safe sex (rs = -,134, p =,020), furthermore, a regression analysis showed that the perception of risk for HIV has a predictive effect on safe sex (ß = -, 143, F = 6,27 [gl=1,300], p = 0,013), CONCLUSION: Migrants are a group that requires interest in the field of research related to sexuality, despite being a vulnerable group and identified as at risk, their perception of acquiring HIV is low, this variable should be considered of importance in future research in the sexual field of migrants, because it can be used in conjunction with others as a model or as a mediator.


Subject(s)
HIV Infections , Transients and Migrants , Cross-Sectional Studies , Female , HIV Infections/epidemiology , Humans , Male , Mexico/epidemiology , Middle Aged , Perception , Safe Sex
15.
Int J Psychol Res (Medellin) ; 15(1): 30-41, 2022.
Article in English | MEDLINE | ID: mdl-36199522

ABSTRACT

In Mexico, young people continue to experience problems due to a lack of correct and consistent condom use during sexual intercourse. OBJECTIVE: to evaluate the effect of a randomized controlled clinical trial with the use of smartphones to increase safe sex intentions and safe sexual behavior. METHODS: experimental design with two treatment groups with 177 young people who requested the rapid HIV test in a non-governmental organization in the city of Monterrey, Mexico. The experimental group was given Respect M-Health with the use of mobile devices; the control group was given similar counseling without the use of mobile technology and 8 pencil and paper instruments were used. RESULTS: the effect of the experimental group was greater in safe sexual behavior reflected in the means at pre-test M=64.80 (SD=1.86), post-test M=85.33 (SD=1.54), and at 30 days M=87.40 (SD=1.52), and in the safe sex intentions factor at pre-test M=78.50 (SD=3.07), post-test M=94.70 (SD=2.46), and at 30 days M=95.74 (SD=2.29). CONCLUSIONS: Smartphone use was an effective tool as a support to increase safe sexual behavior in youth.


En México, los jóvenes siguen presentando problemas debido a la falta de uso correcto y consistente del preservativo durante las relaciones sexuales. OBJETIVO: evaluar el efecto de un ensayo clínico controlado y aleatorizado con el uso de teléfonos inteligentes para aumentar las intenciones de sexo seguro y la conducta sexual segura. Métodos: diseño experimental con dos grupos de tratamiento con 177 jóvenes que solicitaron la prueba rápida de VIH en una Organización no Gubernamental en la ciudad de Monterrey, México. Al grupo experimental se le brindó Respeto M-Salud para el uso de dispositivos móviles; al grupo control se le entregó una herramienta similar, pero sin el uso de tecnología móvil, y se utilizaron 8 instrumentos de lápiz y papel. RESULTADOS: el efecto del grupo experimental fue mayor en la conducta sexual segura reflejado en las medias del pre-test M=64.80 (SD=1.86), post-test M=85.33 (SD=1.54) y a los 30 días M=87.40 (SD=1.52); y en el factor de intenciones de sexo seguro, se reflejó de esta manera en el pre-test M=78.50 (SD=3.07), post-test M=94.70 (SD=2.46) y a los 30 días M=95.74 (SD=2.29). CONCLUSIONES: El uso de teléfonos inteligentes fue una herramienta eficaz como apoyo para aumentar la conducta sexual segura en los jóvenes.

16.
NPJ Breast Cancer ; 8(1): 126, 2022 Nov 29.
Article in English | MEDLINE | ID: mdl-36446794

ABSTRACT

Despite the biological and therapeutic relevance of CDK4/6 for the treatment of HR+, HER2- advanced breast cancer, the detailed mode of action of CDK4/6 inhibitors is not completely understood. Of particular interest, phosphorylation of CDK4 at T172 (pT172) is critical for generating the active conformation, yet no such crystal structure has been reported to date. We describe here the x-ray structure of active CDK4-cyclin D3 bound to the CDK4/6 inhibitor abemaciclib and discuss the key aspects of the catalytically-competent complex. Furthermore, the effect of CDK4/6 inhibitors on CDK4 T172 phosphorylation has not been explored, despite its role as a potential biomarker of CDK4/6 inhibitor response. We show mechanistically that CDK4/6i stabilize primed (pT172) CDK4-cyclin D complex and selectively displace p21 in responsive tumor cells. Stabilization of active CDK4-cyclin D1 complex can lead to pathway reactivation following alternate dosing regimen. Consequently, sustained binding of abemaciclib to CDK4 leads to potent cell cycle inhibition in breast cancer cell lines and prevents rebound activation of downstream signaling. Overall, our study provides key insights demonstrating that prolonged treatment with CDK4/6 inhibitors and composition of the CDK4/6-cyclin D complex are both critical determinants of abemaciclib efficacy, with implications for this class of anticancer therapy.

17.
PLoS One ; 16(5): e0249877, 2021.
Article in English | MEDLINE | ID: mdl-33970929

ABSTRACT

INTRODUCTION: The Curitiba (Brazil)-based Project, A Hora é Agora (AHA), evaluated a comprehensive HIV control strategy among men who have sex with men (MSM) aimed at expanding access to HIV rapid testing and linking HIV-positive MSM to health services and treatment. AHA's approach included rapid HIV Testing Services (HTC) in one mobile testing unit (MTU); a local, gay-led, non-governmental organization (NGO); an existing government-run health facility (COA); and Internet-based HIV self-testing. The objectives of the paper were to compare a) number of MSM tested in each strategy, its positivity and linkage; b) social, demographic and behavioral characteristics of MSM accessing the different HTC and linkage services; and c) the costs of the individual strategies to diagnose and link MSM to services. METHODS: We used data for 2,681 MSM tested at COA, MTU and NGO from March 2015 to March 2017. This is a cross sectional comparison of the demographics and behavioral factors (age group, race/ethnicity, education, sexually transmitted diseases, knowledge of AHA services and previous HIV test). Absolute frequencies, percentage distributions and confidence intervals for the percentages were used, as well as unilateral statistical tests. RESULTS AND DISCUSSION: AHA performed 2,681 HIV tests among MSM across three in-person strategies: MTU, NGO, and COA; and distributed 4,752 HIV oral fluid tests through the self-testing platform. MTU, NGO and COA reported 365 (13.6%) HIV positive diagnoses among MSM, including 28 users with previous HIV diagnosis or on antiretroviral treatment for HIV. Of these, 89% of MSM were eligible for linkage-to-care services. Linkage support was accepted by 86% of positive MSM, of which 66.7% were linked to services in less than 90 days. The MTU resulted in the lowest cost per MSM tested ($137 per test), followed by self-testing ($247). CONCLUSIONS: AHA offered MSM access to HTC through innovative strategies operating in alternative sites and schedules. It presented the Curitiba HIV/AIDS community the opportunity to monitor HIV-positive MSM from diagnosis to treatment uptake. Self-testing emerged as a feasible strategy to increase MSM access to HIV-testing through virtual tools and anonymous test kit delivery and pick-up. Cost per test findings in both the MTU and self-testing support expansion to other regions with similar epidemiological contexts.


Subject(s)
HIV Infections/diagnosis , HIV Testing , Homosexuality, Male , Adult , Brazil , Costs and Cost Analysis , HIV Infections/economics , HIV Testing/economics , Humans , Internet , Male , Young Adult
18.
Cien Saude Colet ; 26(suppl 2): 3543-3554, 2021.
Article in Portuguese, English | MEDLINE | ID: mdl-34468650

ABSTRACT

This study aimed to evaluate the risk of HIV infection in men who have sex with men (MSM) by developing an index that considers sex partner networks. The index variables were age, ethnicity/skin color, schooling, relationship type, condom use in receptive and insertive relationships, self-perception of the possibility of HIV infection, sexually transmitted infections, and rapid HIV testing results. We used data from a cross-sectional MSM egocentric network survey conducted in Rio de Janeiro between 2014 and 2015. The initial research volunteer is called ego, each partner is called alter, and each pair of people in a relationship is called the dyad. Multiple logistic regression was used to define the coefficients of the equations for the elaboration of the indices. The index ranged from 0 to 1; the closer to 1, the higher the risk of HIV infection. HIV prevalence was 13.9% among egos. The mean egos index with an HIV-reactive test was 57% higher than non-reactive, and the same profile was observed in the index values of dyads. The index allowed the incorporation of network data through the dyads and contributed to the identification of individuals with a higher likelihood of acquiring HIV.


O objetivo do estudo foi avaliar o risco de infecção por HIV em homens que fazem sexo com homens (HSH) a partir do desenvolvimento de um índice que considere as redes de parceiros sexuais. As variáveis do índice foram faixa etária, raça/cor, escolaridade, tipo de relacionamento, uso de preservativo em relações receptivas e insertivas, autopercepção da chance de se infectar pelo HIV, história de infecções sexualmente transmissíveis, além dos resultados dos testes rápidos para HIV. Foram utilizados dados de uma pesquisa de rede egocêntricas HSH, com desenho transversal, realizada no Rio de Janeiro entre 2014 e 2015. O voluntário inicial da pesquisa é denominado ego, cada parceiro é alter, e cada par de pessoas em um relacionamento é a díade. Utilizou-se regressão logística múltipla para definição dos coeficientes das equações para elaboração dos índices. O índice variou de 0 a 1, quanto mais próximo de 1, maior o risco de infecção por HIV. A prevalência de HIV dos egos foi de 13,9%. A média do índice dos egos com teste HIV reagente foi 57% maior do que aqueles não reagentes, o mesmo perfil foi observado nos valores dos índices das díades. O índice permitiu incorporar os dados das redes por meio das díades e contribuiu para a identificação de indivíduos com maior chance de aquisição do HIV.


Subject(s)
HIV Infections , Sexual and Gender Minorities , Brazil/epidemiology , Cross-Sectional Studies , HIV Infections/epidemiology , Homosexuality, Male , Humans , Male , Risk Assessment , Sexual Behavior , Sexual Partners
19.
Cien Saude Colet ; 26(6): 2183-2194, 2021 Jun.
Article in English, Spanish | MEDLINE | ID: mdl-34231730

ABSTRACT

A scoping literature review to identify the multilevel HIV serosorting related elements was developed. Articles from EBSCO, PubMed, PsyNET and Science Direct with serosort* or serosorting at the tittle or abstract, written in English or Spanish were included. No restriction in type of population or design were applied. 239 records were retrieved after duplicates removed, but 181 references were extracted for full-text review. Individual level: HIV knowledge, serostatus, risk perceptions, abilities to disclose and for condom use negotiation, motivations, use of drugs, stigma, attitudes toward condom use, and perceptions/beliefs about the HIV and related treatments, HIV infection rates/testing and behavioral factors. Interpersonal level: social networks, abilities (sexual behavior negotiation, and communication). Community level: stigma, social norms, access to HIV related services. Structural level: political context, HIV related funding and public policies. HIV Serosorting is not solely an interpersonal behavior it involves multilevel elements that must be acknowledged by professionals and stakeholders.


Subject(s)
HIV Infections , Condoms , HIV Infections/epidemiology , HIV Serosorting , Homosexuality, Male , Humans , Male , Safe Sex , Sexual Behavior , Sexual Partners
20.
Hisp Health Care Int ; 19(1): 63-68, 2021 03.
Article in English | MEDLINE | ID: mdl-32406753

ABSTRACT

BACKGROUND: The parental role is key for the prevention of human papillomavirus (HPV) in adolescents; however, there are factors that can facilitate or inhibit its performance. For this reason, the purpose of this study was to determine the factors that influence the role of parents for prevention of HPV in their adolescent children. METHOD: A descriptive correlational study design included a convenience sample of 582 Mexican parents, whose son or daughter, 13 to 15 years of age, was in either the second or third year of high school. Data analyses included multiple linear regression. RESULTS: Factors related to the role of parents included knowledge about HPV (rs = 0.180, p < .01), perceived risk to contract HPV (rs = 0.148, p < .01), self-efficacy for sexual communication with adolescents (rs = 0.507, p < .01), and attitude toward prevention of HPV (rs = 0.272, p < .01). Self-efficacy for sexual communication with adolescents and attitude toward prevention of HPV positively influenced the parental role, explaining 28.8% of the variance, F(4, 577) = 59.80, p < .001. CONCLUSIONS: Parents with positive attitudes regarding prevention of HPV and who perceive self-efficacy in communicating sexuality issues with their adolescent children, develop a preventative role.


Subject(s)
Alphapapillomavirus , Papillomavirus Infections , Papillomavirus Vaccines , Adolescent , Child , Health Knowledge, Attitudes, Practice , Humans , Nuclear Family , Papillomaviridae , Papillomavirus Infections/prevention & control , Parents , Patient Acceptance of Health Care , Vaccination
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