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BACKGROUND: Epidemiological investigations have revealed an important association between infection, inflammation and prostate cancer. Certain bacterial species, such as Klebsiella spp, Escherichia coli, Pseudomonas spp, Proteus mirabilis, Chlamydia trachomatis have been linked to prostate cancer. This study aimed to examine the microbiota; specifically bacterial species that have been linked to prostate infections in the urine of individuals diagnosed with prostate cancer. RESULTS: Sixty-six prostate cancer patients and forty controls provided midstream urine samples. The urine samples were grown on suitable medium, and bacterial isolates were detected by standard microbiological methods. Additionally, the antibiotic sensitivity pattern of the bacterial isolates was analysed. A total of number of 72 bacterial isolates were obtained from the urine of study participants. The results showed the presence of Escherichia coli (50.0%), Pseudomonas aeruginosa (18.1%), Klebsiella spp (15.3%), Staphylococcus aureus (8.3%), Enterobacter spp (4.2%), and Proteus mirabilis (2.8%) in the urine. The most common bacterial species isolated from prostate cancer patients was Escherichia coli, which was susceptible to levofloxacin (100%), tobramycin (91.7%), and amikacin (62.5%). CONCLUSIONS: This study's findings established the presence of bacteria previously linked to prostatitis. This report indicates a high prevalence of pro-inflammatory bacteria and uropathogens in the urinary tract of men diagnosed with prostate cancer.
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Antibacterianos , Bacterias , Pruebas de Sensibilidad Microbiana , Hiperplasia Prostática , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/microbiología , Antibacterianos/farmacología , Hiperplasia Prostática/microbiología , Persona de Mediana Edad , Prevalencia , Anciano , Nigeria/epidemiología , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/clasificación , Infecciones Urinarias/microbiología , Infecciones Urinarias/epidemiología , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Klebsiella/efectos de los fármacos , Klebsiella/aislamiento & purificación , Proteus mirabilis/efectos de los fármacos , Proteus mirabilis/aislamiento & purificación , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificaciónRESUMEN
Colorectal cancer (CRC) is the third most common cancer and third leading cause of cancer-related death among African Americans in the United States. However, when detected early, CRC is treatable and survival rates are high. CRC health disparities for African Americans compared with other groups may be due in part to lower screening adherence and later stage diagnosis. The objective of this research phase was to test predictors of ever having received CRC screening (i.e., self-report of lifetime receipt of CRC screening) using survey measures in the domains of healthcare communication, trust in doctors, CRC perceived susceptibility, CRC worry, negative cancer beliefs, CRC screening self-efficacy, and cultural constructs for CRC screening in a sample of African American community health center patients. The study recruited 115 African American patients between the ages of 45 to 64 years old from community health centers in north Florida to complete the baseline survey. Our results show significant differences in CRC screening history by age, marital status, level of mistrust of healthcare providers, and level of empowerment toward cancer screening. To increase CRC screening in this population, the study findings suggest development of intervention programs that focus on priority populations of younger, unmarried African Americans, especially given the current trend of early onset CRC. Moreover, survival rates are lower for unmarried and younger African Americans relative to older and married individuals. Such interventions should also aim to increase trust in healthcare providers and increase empowerment for CRC screening decision making to increase screening participation.
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Negro o Afroamericano , Neoplasias Colorrectales , Humanos , Estados Unidos , Persona de Mediana Edad , Detección Precoz del Cáncer , Actitud Frente a la Salud , Conocimientos, Actitudes y Práctica en Salud , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/prevención & control , Tamizaje MasivoRESUMEN
Background: Androgenetic alopecia (AGA) has been linked to cardiovascular diseases (CVDs) and metabolic syndrome (MetS). Works on AGA, cardiovascular risk factors (CVRFs) and MetS are rare among Nigerians. Aim: This study set out to determine the relationship among CVRFs, MetS, and AGA. Subjects and Methods: This is a cross-sectional study done among adults who were 18 years and above in selected communities in Ogbomoso on 260 consenting AGA participants as well as 260 age controls without AGA. They were matched for age and sex using a multistage sampling method. Anthropometric measurements, fasting blood glucose, and lipid profile samples were collected. MetS was diagnosed using International Diabetes Federation criteria. Data were analyzed using IBM SPSS version 20. Ethical approval was gotten before commencement of the study (LTH/OGB/EC/2017/162). Result: Metabolic syndrome in AGA was higher than in controls (8.08% vs. 7.69%, p = 0.742). AGA was significantly associated with elevated mean systolic blood pressure (SBP) (p = 0.008), low High Density Lipoprotein (HDL-c) (p < 0.001), alcohol intake (p < 0.001), dyslipidaemia (p = 0.002), and sedentary lifestyle (p = 0.010). The correlates of AGA severity in male and female gender are age (p < 0.001 and 0.009 respectively), SBP (p = 0.024) and abdominal obesity (p = 0.027) in male gender. Conclusion: AGA in Nigerians is associated with dyslipidaemia, alcohol intake, and sedentary lifestyle. AGA severity is related to age, higher mean SBP, abdominal obesity and low HDL-c in male and age, and Body mass index in females. Nigerians with AGA should be screened for dyslipidaemia and counseled against the use of alcohol and sedentary lifestyle.
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Enfermedades Cardiovasculares , Dislipidemias , Síndrome Metabólico , Humanos , Adulto , Masculino , Femenino , Síndrome Metabólico/epidemiología , Síndrome Metabólico/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/complicaciones , Factores de Riesgo , Obesidad Abdominal/complicaciones , Obesidad Abdominal/epidemiología , Estudios Transversales , Obesidad/complicaciones , Factores de Riesgo de Enfermedad Cardiaca , Dislipidemias/epidemiología , Dislipidemias/complicaciones , Alopecia/complicaciones , Alopecia/diagnósticoRESUMEN
INTRODUCTION: Traumatic brain injury (TBI) is a significant source of morbidity and mortality in the United States. Recent shifts in state legislation have increased the use of recreational and medical marijuana. While cannabinoids and tetrahydrocannabinol (THC) have known anti-inflammatory effects, the impact of preinjury THC use on clinical outcomes in the setting of severe TBI is unknown. We hypothesized that preinjury THC use in trauma patients suffering TBI would be associated with decreased thromboembolic events and adverse outcomes. METHODS: The American College of Surgeons Trauma Quality Improvement Program was used to identify patients aged ≥18 y with TBI and severe injury (Injury Severity Score ≥ 16) in admit year 2017. Patients with smoking or tobacco history or missing or positive toxicology tests for drug and/or alcohol use other than THC were excluded. Propensity score matching was used to compare THC+ patients to similar THC- patients. RESULTS: A total of 13,266 patients met inclusion criteria, of which 1669 were THC+. A total of 1377 THC+ patients were matched to 1377 THC- patients. No significant differences were found in in-hospital outcomes, including mortality, length of stay, cardiac arrest, pulmonary embolism, deep vein thrombosis, or acute respiratory distress syndrome. No patients had ischemic stroke, and THC+ patients had significantly decreased rates of hemorrhagic stroke (0.5% versus 1.5%, P = 0.02, odds ratio 0.41 [95% confidence interval 0.18-0.86]). CONCLUSIONS: Preinjury THC use may be associated with decreased hemorrhagic stroke in severely injured patients with TBI, but there was no difference in thromboembolic outcomes. Further research into pathophysiological mechanisms related to THC are needed.
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Lesiones Traumáticas del Encéfalo , Cannabinoides , Accidente Cerebrovascular Hemorrágico , Lesiones Traumáticas del Encéfalo/complicaciones , Dronabinol/efectos adversos , Humanos , Puntaje de Gravedad del Traumatismo , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: The human Papillomavirus (HPV) vaccine has demonstrated efficacy in the prevention of cervical cancer when given in early adolescence. The recommendation of the vaccine by health care workers (HCW) is crucial to the uptake of the vaccine by adolescents and the process of this recommendation is important as it determines subsequent uptake of the vaccine. Understanding of the facilitators and barriers of recommendation of this vaccine can help in the development of strategies to improve its recommendation rates and uptake. This study therefore explored the facilitators and barriers for the recommendation of HPV vaccine for adolescents by HCW in Ibadan, Nigeria using the Theoretical Domain Framework (TDF). METHODS: Key informant interviews were conducted with 14 purposively selected HCW who were in charge of vaccination. Content analysis was used after deductive coding of the data using the domains of the TDF. Relevant concepts for facilitators and barriers of HPV vaccine recommendation and quotes were then identified. RESULTS: Mean age of the HCW was 47.7 ± 6.5 years and they consisted of eight nurses, four medical doctors, one medical social worker and one health visitor. Ten domains of the TDF were represented among the facilitators and barriers against the recommendation of HPV vaccination by the HCW, except the goals; memory, attention, decision process; emotion; and behavioral regulation domains. The domains with the highest frequency of concepts were: knowledge, skills, social/professional role and identity, beliefs about capabilities, beliefs about consequences, intention and environmental context and resources. Domains with conflicting statements in the concept were: environmental context and resources, and beliefs about consequences. While those with perceived strength of concept were: social influences, reinforcement and optimism. CONCLUSION: All the 10 identified domains of the TDF are potential areas of focus for strategies for improving the recommendation of HPV vaccine for adolescents by health care workers in Nigeria and other countries with similar sociocultural settings.
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Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Adolescente , Adulto , Femenino , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Humanos , Persona de Mediana Edad , Nigeria , Infecciones por Papillomavirus/prevención & control , VacunaciónRESUMEN
Colorectal cancer (CRC) is the third most diagnosed cancer in the USA, and African Americans experience disproportionate CRC diagnosis and mortality. Early detection could reduce CRC incidence and mortality, and reduce CRC health disparities, which may be due in part to lower screening adherence and later stage diagnosis among African Americans compared to whites. Culturally tailored interventions to increase access to and uptake of CRC stool-based tests are one effective strategy to increase benefits of screening among African Americans. The objectives of this study were to obtain feedback from African Americans on CRC educational materials being developed for a subsequent behavioral clinical trial and explore participants' knowledge, attitudes, and beliefs about CRC and CRC screening. Seven focus groups were conducted between February and November 2020. Participants were African Americans recruited through community contacts. Four focus groups were held in-person and three were conducted virtually due to Covid-19 restrictions. Participants ranked CRC educational text messages and provided feedback on a culturally tailored educational brochure. A focus group guide with scripted probes was used to elicit discussion and transcripts were analyzed using traditional content analysis. Forty-two African Americans participated. Four themes were identified from focus group discussions: (1) knowledge, attitudes, and beliefs on CRC and CRC screening; (2) reliable sources of cancer education information; (3) cultural factors affecting perspectives on health; and (4) community insights into cancer education. Participant input on the brochure was incorporated in content creation. Engaging African American community members to qualitatively examine cancer prevention has value in improving implementation strategy and planning for behavioral clinical trials.
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COVID-19 , Neoplasias Colorrectales , Negro o Afroamericano , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/prevención & control , Detección Precoz del Cáncer , Grupos Focales , Conocimientos, Actitudes y Práctica en Salud , Humanos , Tamizaje MasivoRESUMEN
The effects of phenytoin (PHT), levetiracetam (LEV) or their adjunctive treatment on the hypothalamic-pituitary-testicular axis in male Wistar rats were determined. Twenty-eight male rats (150-180 g) were randomised into four groups (N = 7). Groups I to IV received intraperitoneal treatment of either normal saline (0.2 ml i.p) or PHT (50 mg/kg i.p) or LEV (50 mg/kg) or PHT (25 mg/kg) and LEV (25 mg/kg) combination for 28 days. The organ weight, concentrations of reproductive hormones and semen profile were determined, while the brain, epididymis and testis were preserved in 10% neutral-buffered formalin for the histomorphological study. Data were analysed using descriptive and inferential statistics. The results were presented as mean ± SEM in graphs or tables, while the level of significance was taken at p < .05. The semen profile was altered significantly in all the treatment groups. The gonadotrophic releasing hormone, luteinising hormone and testosterone concentration decreased significantly in the PHT- and PHT + LEV-treated groups compared with control. There were various disruptions in the hypothalamus, pituitary and testis of the PHT- and PHT + LEV adjunctive-treated rats. In conclusion, chronic PHT + LEV treatment may pose deleterious effects on the hypothalamic-pituitary-testicular axis than single treatment of either of the two drugs in male rats.
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Fenitoína , Piracetam , Animales , Anticonvulsivantes/farmacología , Levetiracetam , Masculino , Fenitoína/farmacología , Ratas , Ratas Wistar , TestículoRESUMEN
OBJECTIVES: To quantify the epidemiology of bladder cancer in Africa to guide a targeted public health response and support research initiatives. METHODS: We systematically searched publicly available sources for population-based registry studies reporting the incidence of bladder cancer in Africa between January 1980 and June 2017. Crude incidence rates of bladder cancer were extracted. A Bayesian network meta-analysis model was used to estimate incidence rates. RESULTS: The search returned 1328 studies. A total of 22 studies carried out across 15 African countries met our pre-defined selection criteria. Heterogeneity across studies was high (I2 = 98.9%, P < 0.001). The pooled incidence of bladder cancer in Africa was 7.0 (95% credible interval 5.8-8.3) per 100 000 population in men and 1.8 (95% credible interval 1.2-2.6) per 100 000 in women. The incidence of bladder cancer was consistently higher in North Africa in both sexes. Among men, we estimated a pooled incidence of 10.1 (95% credible interval 7.9-11.9) per 100 000 in North Africa and 5.0 (95% credible interval 3.8-6.6) per 100 000 in sub-Saharan Africa. In women, the pooled incidence was 2.0 (95% credible interval 1.0-3.0) per 100 000 and 1.5 (95% credible interval 0.9-2.0) per 100 000 in North Africa and sub-Saharan Africa, respectively. Incidence rates increased significantly among men from 5.6 (95% credible interval 4.2-7.2) in the 1990s to 8.5 (95% credible interval 6.9-10.1) per 100 000 in 2010. CONCLUSIONS: The present study suggests a growing incidence of bladder cancer in Africa in recent years, particularly among men and in North Africa. This study also highlights the lack of quality data sources and collection of essential clinical and epidemiological data in several African countries, and this hinders public health planning.
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Neoplasias de la Vejiga Urinaria/epidemiología , África/epidemiología , Teorema de Bayes , Femenino , Humanos , Incidencia , Masculino , Distribución por SexoRESUMEN
In utero hypoxia influences the structure and function of most fetal arteries, including those of the developing cerebral circulation. Whereas the signals that initiate this hypoxic remodeling remain uncertain, these appear to be distinct from the mechanisms that maintain the remodeled vascular state. The present study explores the hypothesis that chronic hypoxia elicits sustained changes in fetal cerebrovascular reactivity to endothelin-1 (ET-1), a potent vascular contractant and mitogen. In fetal lambs, chronic hypoxia (3,820-m altitude for the last 110 days of gestation) had no significant effect on plasma ET-1 levels or ETA receptor density in cerebral arteries but enhanced contractile responses to ET-1 in an ETA-dependent manner. In organ culture (24 h), 10 nM ET-1 increased medial thicknesses less in hypoxic than in normoxic arteries, and these increases were ablated by inhibition of PKC (chelerythrine) in both normoxic and hypoxic arteries but were attenuated by inhibition of CaMKII (KN93) and p38 (SB203580) in normoxic but not hypoxic arteries. As indicated by Ki-67 immunostaining, ET-1 increased medial thicknesses via hypertrophy. Measurements of colocalization between MLCK and SMαA revealed that organ culture with ET-1 also promoted contractile dedifferentiation in normoxic, but not hypoxic, arteries through mechanisms attenuated by inhibitors of PKC, CaMKII, and p38. These results support the hypothesis that chronic hypoxia elicits sustained changes in fetal cerebrovascular reactivity to ET-1 through pathways dependent upon PKC, CaMKII, and p38 that cause increased ET-1-mediated contractility, decreased ET-1-mediated smooth muscle hypertrophy, and a depressed ability of ET-1 to promote contractile dedifferentiation.
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Diferenciación Celular/genética , Arterias Cerebrales/metabolismo , Endotelina-1/genética , Hipoxia/metabolismo , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Arterias Cerebrales/embriología , Endotelina-1/administración & dosificación , Endotelina-1/sangre , Femenino , Feto/irrigación sanguínea , Feto/metabolismo , Hipoxia/sangre , Hipoxia/fisiopatología , Contracción Muscular/efectos de los fármacos , Contracción Muscular/genética , Técnicas de Cultivo de Órganos , Embarazo , Proteína Quinasa C/genética , Ovinos , Remodelación Vascular/efectos de los fármacos , Remodelación Vascular/genética , Vasoconstricción/efectos de los fármacos , Vasoconstricción/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genéticaRESUMEN
Fetal hypoxia triggers compensatory angiogenesis and remodeling through mechanisms not fully elucidated. In response to hypoxia, hypoxia-inducible factor drives expression of cytokines that exert multiple effects on cerebral structures. Among these, the artery wall is composed of a heterogeneous cell mix and exhibits distinct patterns of cellular differentiation and reactivity. Governing these patterns are the vascular endothelium, smooth muscle (SM), adventitia, sympathetic perivascular nerves (SPN), and the parenchyma. Although an extensive literature details effects of nonneuronal factors on cerebral arteries, the trophic role of perivascular nerves remains unclear. Hypoxia increases sympathetic innervation with subsequent release of norepinephrine (NE), neuropeptide-Y (NPY), and adenosine triphosphate, which exert motor and trophic effects on cerebral arteries and influence dynamic transitions among SM phenotypes. Our data also suggest that the cerebrovasculature reacts very differently to hypoxia in fetuses and adults, and we hypothesize that these differences arise from age-related differences in arterial SM phenotype reactivity and proximity to trophic factors, particularly of neural origin. We provide an integration of recent literature focused on mechanisms by which SPN mediate hypoxic remodeling. Our recent findings suggest that trophic effects of SPN on cerebral arteries accelerate functional maturation through shifts in SM phenotype in an age-dependent manner.
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Circulación Cerebrovascular , Hipoxia Fetal , Hipoxia Encefálica , Músculo Liso Vascular , Sistema Nervioso Simpático , Remodelación Vascular , Adenosina Trifosfato/metabolismo , Adulto , Factores de Edad , Animales , Hipoxia Fetal/complicaciones , Hipoxia Fetal/metabolismo , Hipoxia Fetal/fisiopatología , Humanos , Hipoxia Encefálica/complicaciones , Hipoxia Encefálica/metabolismo , Hipoxia Encefálica/fisiopatología , Músculo Liso Vascular/inervación , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Músculo Liso Vascular/fisiopatología , Neovascularización Patológica/etiología , Neovascularización Patológica/metabolismo , Neovascularización Patológica/fisiopatología , Neuropéptido Y/metabolismo , Norepinefrina/metabolismo , Sistema Nervioso Simpático/metabolismo , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
The aim of the study was to compare the efficacy of sublingual misoprostol in addition to intravenous oxytocin, with oxytocin alone, in reducing blood loss during and following caesarean section. A total of 120 women undergoing caesarean delivery at the University College Hospital, Ibadan, were randomised into two equal groups. In Group A, 20 IU of intravenous oxytocin was given after umbilical cord clamping, while in Group B, the women received 400 µg misoprostol sublingually and 20 IU oxytocin intravenously. The outcome measures were blood loss, additional uterotonics, change in packed cell volume and side-effect profile. Associations between variables were determined by the χ(2) and Student's t-test. Relative risks were calculated for side-effects; the level of significance was p < 0.05. Intraoperative and postoperative blood loss were significantly lower in Group B (451.3 ml vs 551.2 ml, p = 0.007; 22.7 vs 42.2 ml, p < 0.001, respectively). In Group B, women were 7.4 (p < 0.001) and 9.0 (p = 0.008) times more likely to experience shivering and fever, respectively. The need for additional uterotonics was greater in the oxytocin group (66.7% vs 27.6%, p < 0.001). The addition of sublingual misoprostol to intravenous oxytocin reduces postpartum blood loss and the need for additional uterotonics. There is however, an increased risk of shivering and fever with this combination.
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Cesárea/efectos adversos , Misoprostol/administración & dosificación , Oxitócicos/administración & dosificación , Hemorragia Posoperatoria/prevención & control , Administración Sublingual , Adulto , Quimioterapia Combinada , Femenino , Fiebre/inducido químicamente , Humanos , Misoprostol/efectos adversos , Oxitócicos/efectos adversos , Oxitocina/uso terapéutico , Hemorragia Posoperatoria/etiología , Embarazo , Tiritona , Adulto JovenRESUMEN
This retrospective cross-sectional study evaluated the applicability of the universal grading system in a selected patient population and compared the results with the FIGO staging. A total of 49 patients who met the inclusion criteria, were studied. The slides were independently examined by two pathologists, using Silverberg's parameters. The prognostic value of their findings was analysed using Kaplan-Meier graphs. Papillary subtype and abnormal nuclear features were the most frequent histological pattern and a younger age was associated with improved survival. The longest surviving patient (250 weeks) had the lowest mitotic activity, predominantly glandular architecture and little or no nuclear pleomorphism, the reverse is the case for the shortest-term survivor (120 weeks). The universal grading system is useful and comparable with the FIGO staging. The two systems are complementary.
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Carcinoma/mortalidad , Neoplasias Ováricas/mortalidad , Adulto , Anciano , Carcinoma/patología , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Nigeria/epidemiología , Neoplasias Ováricas/patología , Ovario/patología , Proyectos Piloto , Estudios RetrospectivosRESUMEN
Background: Aminoglycosides, such as Streptomycin, are cheap, potent antibiotics widely used Sub-Saharan Africa. However, aminoglycosides are the commonest cause of ototoxicity. The limited prospective epidemiological studies on aminoglycoside ototoxicity from Sub-Saharan Africa motivated this study to provide epidemiological information on Streptomycin-induced ototoxicity, identify risk factors and predictors of ototoxicity. Method: A longitudinal study of 153 adults receiving Streptomycin-based anti-tuberculous drugs was done. All participants underwent extended frequency audiometry and had normal hearing thresholds at baseline. Hearing thresholds were assessed weekly for 2 months, then monthly for the subsequent 6 months. Ototoxicity was determined using the ASHA criteria. Descriptive statistics were used to analyze socio-demographic variables. Ototoxicity incidence rate was calculated, and Kaplan-Meier estimate used to determine cumulative probability of ototoxicity. Chi-square test was done to determine parameters associated with ototoxicity and Cox regression models were used to choose the predictors of ototoxicity. Results: Age of participants was 41.43 ± 12.66 years, with a male-to-female ratio of 1:0.6. Ototoxicity was found in 34.6% of the participants, giving an incidence of 17.26 per 1,000-person-week. The mean onset time to ototoxicity was 28.0 ± 0.47 weeks. By 28th week, risk of developing ototoxicity for respondents below 40 years of age was 0.29, and for those above 40 years was 0.77. At the end of the follow-up period, the overall probability of developing ototoxicity in the study population was 0.74. A significant difference in onset of ototoxicity was found between the age groups: the longest onset was seen in <40 years, followed by 40-49 years, and shortest onset in ≥50 years. Hazard of ototoxicity was significantly higher in participants aged ≥50 years compared to participants aged ≤40 years (HR = 3.76, 95% CI = 1.84-7.65). The probability of ototoxicity at 40 g, 60 g and 80 g cumulative dose of Streptomycin was 0.08, 0.43 and 2.34, respectively. Age and cumulative dose were significant predictors of ototoxicity. Conclusion: The mean onset time to Streptomycin-induced ototoxicity was 28 weeks after commencement of therapy. Age and cumulative dose can reliably predict the onset of Streptomycin-induced ototoxicity. Medium to long term monitoring of hearing is advised for patients on aminoglycoside therapy.
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BACKGROUND: Doravirine and islatravir is an investigational, once-daily regimen with high antiviral potency, favourable safety and tolerability, and a low propensity for resistance. We investigated a switch from bictegravir, emtricitabine, and tenofovir alafenamide to doravirine (100 mg) and islatravir (0·75 mg) in virologically suppressed adults with HIV-1. METHODS: We conducted a phase 3, multicentre, randomised, active-controlled, double-blind, double-dummy, non-inferiority trial at 89 research, community, and hospital-based clinics in 11 countries. Adults aged 18 years or older with fewer than 50 HIV-1 RNA copies per mL for at least 3 months on bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) and no history of previous virological failure on any past or current regimen were randomly assigned (1:1) by a computer-generated randomisation allocation schedule, with block randomisation based on a block size of four, to switch to doravirine (100 mg) and islatravir (0·75 mg) or continue bictegravir, emtricitabine, and tenofovir alafenamide orally once daily, with matching placebos taken by all participants. Participants, investigators, study staff, and sponsor personnel involved in study drug administration or clinical evaluation of participants were masked to treatment assignment until week 48. Participants were instructed at each visit to take one tablet from each of the two bottles received, one of study drug and one of placebo, once daily, and participants were assessed at baseline and weeks 4, 12, 24, 36, and 48. The primary endpoint was the proportion of participants with greater than or equal to 50 HIV-1 RNA copies per mL at week 48 in the full analysis set (ie, all participants who received at least one dose of study drug; US Food and Drug Administration snapshot; prespecified non-inferiority margin 4%). The study is ongoing, with all remaining participants in post-treatment follow-up, and is registered with ClinicalTrials.gov, NCT04223791. FINDINGS: We screened 726 individuals for eligibility between Feb 18 and Sept 3, 2020, of whom 643 (88·6%) participants were randomly assigned to a treatment group (183 [28·5%] women and 460 [71·5%] men). 322 participants were switched to doravirine (100 mg) and islatravir (0·75 mg) and 321 continued bictegravir, emtricitabine, and tenofovir alafenamide (two participants [one with a protocol deviation and one who withdrew] assigned to bictegravir, emtricitabine, and tenofovir alafenamide did not receive treatment). The last follow-up visit for the week 48 analysis occurred on Aug 26, 2021. At week 48, two (0·6%) of 322 participants in the doravirine and islatravir group compared with one (0·3%) of 319 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group had greater than or equal to 50 HIV-1 RNA copies per mL (difference 0·3%, 95% CI -1·2 to 2·0). The per-protocol analysis showed consistent results. 25 (7·8%) participants in the doravirine and islatravir group had headache compared with 23 [7·2%] participants in the bictegravir, emtricitabine, and tenofovir alafenamide group; 101 (31·4%) compared with 98 (30·7%) had infections; and eight (2·5%) participants in each group discontinued therapy due to adverse events. 32 (9·9%) participants had treatment-related adverse events in the islatravir and doravirine group comapred with 38 (11·9%) in the bictegravir, emtricitabine, and tenofovir alafenamide group. In the islatravir and doravirine group, CD4 cell counts (mean change -19·7 cells per µL) and total lymphocyte counts (mean change -0·20 × 109/L) were decreased at 48 weeks. INTERPRETATION: Switching to daily doravirine (100 mg) and islatravir (0·75 mg) was non-inferior to bictegravir, emtricitabine, and tenofovir alafenamide at week 48. However, decreases in CD4 cell and total lymphocyte counts do not support the further development of once-daily doravirine (100 mg) and islatravir (0·75 mg). FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.
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Adenina , Alanina , Fármacos Anti-VIH , Emtricitabina , Infecciones por VIH , VIH-1 , Compuestos Heterocíclicos de 4 o más Anillos , Piridonas , Tenofovir , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Femenino , Masculino , Tenofovir/administración & dosificación , Tenofovir/uso terapéutico , Tenofovir/análogos & derivados , Adulto , Emtricitabina/administración & dosificación , Emtricitabina/uso terapéutico , VIH-1/efectos de los fármacos , VIH-1/genética , Método Doble Ciego , Piridonas/administración & dosificación , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Persona de Mediana Edad , Alanina/administración & dosificación , Adenina/análogos & derivados , Adenina/administración & dosificación , Adenina/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Piperazinas/administración & dosificación , Amidas/administración & dosificación , Carga Viral/efectos de los fármacos , Resultado del Tratamiento , Esquema de Medicación , Desoxiadenosinas , TriazolesRESUMEN
African locust bean (Parkia biglobosa) is a multipurpose leguminous tree species of nutritional and pharmacological value. The plant is widely distributed in Africa and across Nigeria's major agroecological areas (AEAs). Amidst declining cultivation and production, P. biglobosa is genetically threatened in its natural habitats due to overexploitation, deforestation, wildfires and lack of improved tree management practices. Consequently, concerted research efforts directed towards germplasm collection and assessment of genetic relationships are imperative for conserving its genetic resources, sustainable management and selecting promising landraces for breeding programmes. The dataset presents rbcL intraspecific genetic diversity and population structure of 62 P. biglobosa landraces in Nigeria. A relatively high level of diversity and a low degree of nucleotide variability was observed among the landraces. Relatively high values of 642 total allele sites, 601 polymorphic sites, 504 parsimony information sites, 883 total number mutations, 9 haplotypes and 0.55 gene diversity were recorded for the sequence dataset. Low values of 0.35 nucleotide diversity and 5 InDels events were also recorded for the dataset. The gene flow in this dataset demonstrated an extensive exchange of genes between the three populations of P. biglobosa, which influenced the level of genetic differentiation (Gst) between the populations. Significantly low Gst (-0.01) was recorded between the Guinea and Sudan savannah populations, a moderate value (0.03) was recorded between the Sudan savannah and Rainforest populations and a higher Gst value (0.05) was recorded between the Guinea and Rainforest populations. The dataset highlights potential evolutionary dynamics that might influence variations relevant to the breeding and conservation of P. biglobosa in Nigeria and across its range in West and Central Africa.
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Recent studies suggest that vascular endothelial growth factor (VEGF) can modulate smooth muscle phenotype and, consequently, the composition and function of arteries upstream from the microcirculation, where angiogenesis occurs. Given that hypoxia potently induces VEGF, the present study explores the hypothesis that, in fetal arteries, VEGF contributes to hypoxic vascular remodeling through changes in abundance, organization, and function of contractile proteins. Pregnant ewes were acclimatized at sea level or at altitude (3,820 m) for the final 110 days of gestation. Endothelium-denuded carotid arteries from full-term fetuses were used fresh or after 24 h of organ culture in a physiological concentration (3 ng/ml) of VEGF. After 110 days, hypoxia had no effect on VEGF abundance but markedly increased abundance of the Flk-1 (171%) and Flt-1 (786%) VEGF receptors. Hypoxia had no effect on smooth muscle α-actin (SMαA), decreased myosin light chain (MLC) kinase (MLCK), and increased 20-kDa regulatory MLC (MLC(20)) abundances. Hypoxia also increased MLCK-SMαA, MLC(20)-SMαA, and MLCK-MLC(20) colocalization. Compared with hypoxia, organ culture with VEGF produced the same pattern of changes in contractile protein abundance and colocalization. Effects of VEGF on colocalization were blocked by the VEGF receptor antagonists vatalanib (240 nM) and dasatinib (6.3 nM). Thus, through increases in VEGF receptor density, hypoxia can recruit VEGF to help mediate remodeling of fetal arteries upstream from the microcirculation. The results support the hypothesis that VEGF contributes to hypoxic vascular remodeling through changes in abundance, organization, and function of contractile proteins.
Asunto(s)
Arterias Carótidas/metabolismo , Proteínas Contráctiles/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Animales , Arterias Carótidas/embriología , Hipoxia de la Célula , Proteínas Contráctiles/genética , Femenino , Feto/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Neovascularización Fisiológica , Embarazo , Transporte de Proteínas , Receptores de Factores de Crecimiento Endotelial Vascular/genética , Ovinos , Técnicas de Cultivo de Tejidos , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , VasoconstricciónRESUMEN
The knowledge of pregnant women about Hepatitis B virus infection at three different levels of healthcare and their access to screening and vaccination was evaluated by a questionnaire-based cross-sectional study. There were 643 respondents with a mean age of 30.2 ± 5.2 years and mean gestational age of 26.1 ± 8.4 weeks. The distribution of respondents was 55 (8.6%, primary), 204 (31.7%, secondary) and 383 (59.6%, tertiary) women. The majority of respondents were traders (36%) or civil servants/professionals (28.6%). Overall, 76% of all women had inadequate knowledge about hepatitis B infection; 19.5% had been screened, while 9.7% had been vaccinated. There was an increased likelihood of adequate knowledge, previous screening and vaccination among health workers (p = 0.00). Other positive predictors of knowledge and vaccination were tertiary education (p = 0.04) and tertiary care (p = 0.00). There is inadequate knowledge among pregnant women in Ibadan about Hepatitis B infection, with significant differences at the various levels of care, particularly in non-tertiary settings where screening and vaccination is also sub-optimal. Information dissemination, universal screening and vaccination services for pregnant women in Nigeria require urgent consideration.
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Conocimientos, Actitudes y Práctica en Salud , Hepatitis B/prevención & control , Complicaciones Infecciosas del Embarazo/prevención & control , Adolescente , Adulto , Estudios Transversales , Femenino , Hospitales/estadística & datos numéricos , Humanos , Tamizaje Masivo , Nigeria , Embarazo , Atención Prenatal , Vacunación , Adulto JovenRESUMEN
The aim of this research is to explore the use of solar-powered ships (SPS) as a means to reduce greenhouse gas emissions and fossil fuel dependency in the maritime industry. The study focuses on improving the heat transfer efficiency in SPS by employing hybrid nanofluids (HNF) containing carbon nanotubes (CNTs). Additionally, a novel approach utilizing renewable energy and electromagnetic control is proposed to enhance the performance of SPS. The research implements the non-Newtonian Maxwell type and Cattaneo-Christov heat flux model in parabolic trough solar collectors used for ships. The study conducts theoretical experiments and simulations to evaluate the thermal conductivity and viscosity of the CNT-based HNF. Various properties, including solar thermal radiation, viscous dissipation, slippery velocity, and porous media, are assessed to determine the effectiveness of thermal transport in SPS. The research employs similarity variables to simplify the complex partial differential equations into ordinary differential equations and solves them using the Chebyshev collocation spectral method. The results indicate that the MWCNT-SWCNT/EO hybrid nanofluid significantly improves the thermal conductivity, thereby enhancing heat transfer. The HNF exhibits an efficiency rate of approximately 1.78% with a minimum efficiency rate of 2.26%.
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Nanotubos de Carbono , Energía Solar , Calor , Navíos , Fenómenos ElectromagnéticosRESUMEN
OBJECTIVE: This scoping review will present a profile of methodological rigor and reporting quality of clinical practice guidelines for adults hospitalized with bacterial pneumonia. INTRODUCTION: An ideal clinical practice guideline is evidence-based and the product of a rigorous and robust literature-vetted process, yet reports show that rigor is not being achieved. Moreover, a new vulnerable population has been identified due to COVID-19, increasing the need for high quality clinical practice guidelines. Preliminary searches yielded no scoping or systematic reviews on methodological rigor and reporting quality of clinical practice guidelines used for managing bacterial pneumonia in hospitalized adults. INCLUSION CRITERIA: This review will consider current national and international clinical practice guidelines for management of hospitalized adult patients with either suspected or confirmed primary bacterial pneumonia. The review will include adult patients with multiple diagnoses if there is a clearly delineated clinical practice guideline for pneumonia. METHODS: A 3-step search strategy will be conducted using JBI methodology for scoping reviews. After an initial MEDLINE search for keywords, a broad search of 7 databases, 1 simultaneous platform, gray literature, specialty organizations, and international guideline groups will be conducted from 2017 to the present, in any language. Reference lists will be screened for additional sources. A 2-step screening process will be used to identify eligible clinical practice guidelines. Three reviewers will independently extract data using a standardized form. Domain scores will be analyzed and presented as percentages, and the results will be interpreted as map trends. DETAILS OF THIS REVIEW PROJECT ARE AVAILABLE AT: Open Science Framework https://osf.io/eucqy/.
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COVID-19 , Neumonía Bacteriana , Humanos , Adulto , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/terapia , Bases de Datos Factuales , Literatura de Revisión como AsuntoRESUMEN
Paliperidone is an atypical antipsychotic medication commonly used to treat schizophrenia, schizoaffective disorder, and bipolar disorder. It is a metabolite of risperidone and has a similar mechanism of action, primarily blocking dopamine 2 receptors (D2 receptors) in the brain. Paliperidone has various adverse effects, including extrapyramidal symptoms, weight gain, and metabolic disturbances. Catatonia is rare but severe side effects can occur in the context of an underlying psychiatric, neurologic, or general medical condition. Paradoxically, antipsychotics for treating schizophrenia or bipolar spectrum disorders can precipitate or worsen catatonic symptoms. The report suggests that 17-19% of all cases diagnosed as catatonia due to other medical conditions are medication-induced. Catatonia is a neuropsychiatric syndrome that presents as a cluster of psychomotor signs and symptoms resulting in movement and behavior aberrations. Various symptoms, including mutism, stupor, rigidity, and abnormal movements, characterize catatonia. Catatonia is a potentially life-threatening condition requiring prompt recognition and management. Here, we present a case of a patient with catatonia associated with long-acting injectable paliperidone intramuscular therapy in a patient with schizophrenia.