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BACKGROUND AND AIMS: High blood pressure (BP) indices, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP) predict cardiovascular diseases and mortality. However, the association of these BP indices with arterial stiffness (AS) in the normotensive population (BP < 120/80 mmHg) remains unclear. METHODS AND RESULTS: Study participants who underwent health checkups at a tertiary referred center were recruited between November 2018 to December 2019. 2129 participants were enrolled after excluding those aged <18 years old, with elevated BP, history of hypertension, cardiovascular disease, and stroke, or with incomplete data. The brachial-ankle pulse wave velocity (baPWV) values were examined for evaluation of AS. Participants with higher blood pressure indices had significantly higher baPWV. Multiple linear regression revealed that all BP indices were positively associated with baPWV. According to the binary logistic regression analysis, participants in the higher SBP and MAP quartiles were significantly related to AS. The odds ratio (OR) for SBP Q2, Q3 and Q4 vs. Q1 were 6.06, 10.06 and 17.78 whereas the OR for MAP Q2, Q3 and Q4 vs. Q1 were: 5.07, 5.28 and 10.34. For DBP and PP, only participants belonging to the highest quartile were associated with AS(OR for DBP Q4 vs. Q1: 2.51; PP Q4 vs Q1: 1.94). CONCLUSIONS: BP indices were linearly related to the baPWV. Normotensive participants with higher quartiles of SBP, DBP, MAP, and PP, remained associated with increased AS. The SBP and MAP levels exhibited a more prominent relationship with AS.
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Hipertensión , Prehipertensión , Rigidez Vascular , Adulto , Humanos , Adolescente , Presión Sanguínea , Índice Tobillo Braquial , Prehipertensión/diagnóstico , Prehipertensión/epidemiología , Análisis de la Onda del Pulso , Hipertensión/diagnóstico , Hipertensión/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Smoking cessation may lead to depression in some smokers and result in increased risk of suicide. OBJECTIVE: To compare the risk of suicide attempts/behaviors associated with different smoking cessation medications among schizophrenic patients. METHODS: A retrospective cohort study was conducted using General Electric (GE) medical record database (1995-2011). The first day of being prescribed a smoking cessation medication defined as index date. Patients were followed up to one year from index date. Patients' suicide behaviors or attempts were identified through ICD-9 codes and E-codes. Cox proportional hazards model was applied to examine the association between smoking cessation medication and suicidal/self-injurious behaviors. RESULTS: Our cohort consisted of 3925 patients with diagnosis of schizophrenia or schizoaffective disorder who initiated cessation medication. Among them, 104 (2.65%) had suicide attempts or behavior within one-year follow up. However, statistically significant difference in the risk of suicide attempts/behaviors was not detected across cessation regimens in the Cox proportional hazard analysis. Only comorbidity index was found to be associated with suicide, which showed that higher Charlson comorbidity index was associated with higher risks of suicide behaviors within one year (HR=1.15, 95% CI=1.04-1.27). CONCLUSION: There were no significant differences in suicide attempts/behaviors with different cessation medications.
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Esquizofrenia , Psicología del Esquizofrénico , Cese del Hábito de Fumar/métodos , Intento de Suicidio/psicología , Estudios de Seguimiento , Humanos , Estudios Retrospectivos , Factores de Riesgo , Conducta Autodestructiva/prevención & control , Cese del Hábito de Fumar/psicología , Prevención del Hábito de FumarRESUMEN
BACKGROUND: Recent literature suggests an initial increased risk of diabetes following smoking cessation. OBJECTIVES: To compare the risk of developing diabetes among obese smokers who tried to quit smoking using bupropion versus varenicline. METHODS: A population-based retrospective cohort study was conducted using the General Electric (GE) electronic medical record database (2006-2011). The cohort consisted of obese adult smokers without a diabetes diagnosis at baseline and newly initiating use of either bupropion or varenicline. This cohort was then followed for 1 year to observe the risk of developing diabetes. The relative risk of bupropion versus varenicline on developing diabetes was assessed using Cox Proportional Hazards regression model after controlling for covariates. RESULTS: The sample comprised of 78,002 obese smokers of which 1,937 (2.36%) developed diabetes during 1 year follow-up. Diabetes incidence rate was relatively comparable who used varenicline and bupropion (23.50 versus 25.80 per 1,000 person-years). Obese smokers who were prescribed bupropion had a statistically significant higher risk of developing diabetes during 1 year following cessation treatment than those who were prescribed varenicline. ([HR]: 1.58, 95% CI: 1.09-2.27) in the multivariate model. CONCLUSIONS/IMPORTANCE: Obese smokers who were prescribed bupropion might have a higher risk of developing diabetes during 1 year follow up compared to those who were prescribed varenicline. The clinical significance of the finding that bupropion had a higher risk of developing diabetes may need further investigation.
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Bupropión/uso terapéutico , Diabetes Mellitus Tipo 2/epidemiología , Inhibidores de Captación de Dopamina/uso terapéutico , Agonistas Nicotínicos/uso terapéutico , Obesidad/epidemiología , Cese del Hábito de Fumar/métodos , Fumar/tratamiento farmacológico , Vareniclina/uso terapéutico , Adolescente , Adulto , Anciano , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Riesgo , Fumar/epidemiología , Adulto JovenRESUMEN
Background: Bismuth quadruple therapy is currently consensus recommendation for first-line Helicobacter pylori (H. pylori) treatment; however, the optimal duration is unknown. We compared the efficacy of 10-day bismuth quadruple therapy with that of 14-day bismuth quadruple therapy for first-line eradication. Methods: For our multicentre, parallel randomised, open-label, and non-inferiority study, we recruited H. pylori treatment-naïve patients from one medical centre and one teaching hospital in Taiwan. Patients were randomly assigned (1:1) to receive 10-day (PBMT-10) or 14-day (PBMT-14) bismuth quadruple therapy. The primary outcome was the eradication rate as determined by intention-to-treat (ITT) and per-protocol (PP) analyses. The eradication rates between the two groups were compared using a one-sided α value of 0.025 and a non-inferiority margin of 7%. The secondary outcomes were the rate of adverse effects. The trial is registered with ClincialTrials.gov (NCT04527055). Findings: From August 3, 2020 to April 28, 2023, 313 H. pylori treatment-naïve patients (PBMT-10 = 157; PBMT-14 = 156) were enrolled. 35 patients were excluded from PP analyses. The eradication rates (95% CI) for PBMT-10 and PBMT-14 were respectively 92.4% (88.2%-96.5%) and 92.9% (88.9%-97.0%) by ITT analyses, and 97.9% (95.5%-100.0%) and 99.3% (97.8%-100.0%) by PP analyses. The eradication rates for PBMT-10 were non-inferior to those for PBMT-14 (absolute difference [lower boundary of the one-sided 97.5% CI] -0.6% [-6.7%], PNI = 0.020 in ITT analyses, -1.4% [-5.8%], PNI = 0.007 in PP analyses). The rates of overall adverse effects (54.1% versus 57.1%, P = 0.604) were similar between the two groups; nevertheless, the rates of dizziness (18.5% versus 34.0%, P = 0.003) and vomiting (4.5% versus 12.8%, P = 0.008) were lower in PBMT-10 than in PBMT-14. Interpretation: The 10-day bismuth quadruple therapy was non-inferior to the 14-day therapy as a first-line treatment for eradicating H. pylori infection and had no different rates of overall adverse effects, but less serious adverse events in terms of dizziness and vomiting. Funding: The National Science and Technology Council and Ministry of Health and Welfare, Taiwan.
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The objectives were to determine the rate of cigarette smoking and correlates of its use among a sample of Jordanian adults (N = 600). A survey-based, cross-sectional study was conducted with a convenient sample. Logistic regression was used to determine predictors of being a cigarette smoker. Approximately half of the population (45%) had smoked a cigarette in the past month, 40% in the past week, and 36% in past 24 hours. These findings underscore the magnitude of the smoking problem in the Jordanian population and the urgent need for effective interventions. Future research should focus on developing interventions that incorporate the predictors identified.
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Fumar/epidemiología , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Jordania/epidemiología , Modelos Logísticos , Masculino , Adulto JovenRESUMEN
In certain cases, people's health can be compromised or medical treatment delayed as a result of their misplaced belief in false advertisements and purchasing of functional foods. These advertisements can be divided into three distinct types of claims: nutrition, health, and reduction in disease risk. This study analysed how, after consumers realise advertising violations, their intention to purchase functional foods with different claims are affected by the degree of consumer involvement (product, advertising, and situational involvement) and region of residence. A total of 1046 survey responses were collected for analysis. The results reveal that both product and advertising involvement influence purchase intention through the mediation of situational involvement. Residents in nonnorthern regions of Taiwan exhibited a greater effect of overall involvement on purchase intention than did those in the north. In addition, products and advertisements with health claims had a stronger effect on purchase intention than did those with nutrition and disease risk reduction claims. The results indicate that, for functional foods and advertisements with nutrition and health claims, the effects of overall involvement on nonnorthern residents' purchase intentions were greater than those on the northern residents, but for functional foods with disease risk reduction claims, the effects were greater on the northern residents' purchase intentions.
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Plastic cups and bottles used for mineral water packaging may release plastic particles during continuous exposure to heat, light, or unfavorable chemical environments during transportation and storage. Surface-enhanced Raman spectroscopy (SERS) can be used to detect and analyze these plastic particles in a highly sensitive and quantitative manner. In this study, we used copper oxide/silver nanoparticles (CuO/Ag NPs) as the SERS substrate to monitor the release of plastic particles in packaged mineral water samples under irradiation as a function of exposure time. The lower detection limit for plastic particles using this CuO/Ag NP SERS system was 1.6 ng/mL. Our results showed that both plastic cups and bottles released particles under irradiation, however, the plastic cup samples degraded much more readily, with the particle concentration increasing considerably from 5.37 ± 0.11 ng/mL to 3751 ± 0.19 ng/ml over the total exposure time period of 240 min. In this study, we have demonstrated that SERS can provide a highly sensitive, rapid, and economical method for detecting plastic particle contamination caused by degradation of the plastic materials used in mineral water packaging.
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Agua Potable , Nanopartículas del Metal , Agua Potable/análisis , Nanopartículas del Metal/química , Plásticos , Plata/química , Espectrometría Raman/métodosRESUMEN
BACKGROUND: Little is currently known about the association between arterial stiffness and colorectal serrated lesions. This study was aimed toward an investigation of the association between arterial stiffness and colorectal precancerous lesions, including colorectal adenomas and serrated lesions. METHODS: 7262 eligible adult subjects who underwent health check-ups with colonoscopies and brachial-ankle pulse wave velocity (baPWV) were recruited. Patients were categorized as polyp-free, low-risk and high-risk adenomas, and low-risk and high-risk serrated lesions based on the presence of polyps. The severity of arterial stiffness was categorized into four subgroups based on the baPWV quartile. RESULTS: After adjusting for multiple covariates, the baPWV values were found to be positively correlated with the occurrence of low-risk adenomas. With respect to high-risk polyps, the third and highest baPWV quartiles were significantly associated with the occurrence of both high-risk adenomas and high-risk serrated lesions. A more significant association was found in the highest baPWV quartiles combined with smoking in cases classified with high-risk serrated lesions. CONCLUSIONS: Increased arterial stiffness was independently associated with precancerous colorectal lesions, not only adenomas but also high-risk serrated lesions. Individuals with increased arterial stiffness, especially those who are smokers, should be more aware of the risk of colorectal cancer.
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Adenoma , Neoplasias Colorrectales , Lesiones Precancerosas , Rigidez Vascular , Adenoma/epidemiología , Adenoma/patología , Adulto , Índice Tobillo Braquial , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/patología , Estudios Transversales , Humanos , Lesiones Precancerosas/patología , Análisis de la Onda del Pulso , Factores de RiesgoRESUMEN
BACKGROUND: Platelet counts and mean platelet volume (MPV) are related to cardiovascular disease, but a thorough investigation into the connection between increased arterial stiffness, MPV, and platelet counts is lacking. This study aimed to explore the association of platelet count and MPV with arterial stiffness in young and middle-aged adults. METHODS: A total of 2464 participants who underwent health checkups at National Cheng Kung University Hospital, Taiwan from November 2018 to December 2019 were included. We excluded participants aged <18 or >50 years; who are pregnant; on medication for dyslipidemia; with abnormal platelet count, incomplete data, and past history of hematologic disorders. We examined the association of platelet counts and MPV values with brachial-ankle pulse wave velocity (baPWV) levels and increased arterial stiffness. RESULTS: Platelet count was significantly higher in participants with increased arterial stiffness than in those without. The multiple linear regression model revealed that platelet counts were positively associated with baPWV levels (ß = 1.88, 95% confidence interval (CI): 0.96 to 2.80). In the binary logistic regression analysis, subjects in the higher platelet counts quartiles had a higher risk of developing increased arterial stiffness (Q2 vs. Q1: odds ratio (OR): 1.54, 95% CI: 1.05 to 2.27; Q3 vs. Q1: OR: 1.57, 95% CI: 1.06 to 2.33; and Q4 vs. Q1: OR: 2.23, 95% CI: 1.50 to 3.30). In contrast, MPV levels were not associated with arterial stiffness. CONCLUSIONS: Platelet count in midlife was positively associated with baPWV levels. Participants in higher platelet quartiles were at risk for increased arterial stiffness.
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Rigidez Vascular , Humanos , Persona de Mediana Edad , Análisis de la Onda del Pulso , Índice Tobillo Braquial , Recuento de Plaquetas , Valores de Referencia , Factores de RiesgoRESUMEN
Dental compounds and restorative materials undergo surface degradation and erosion from exposure to a variety of dietary substances. In this study we investigated changes in the surface properties of Rebaron, a hard denture reline material (HDRM), following timed immersion in carbonated soft drinks to determine its durability in a common acidic environment. Samples were prepared and immersed in a carbonated soft drink (or its components) for 6, 12, or 24 h. Surface structure and mechanical properties were characterized using Atomic Force Microscopy (AFM). Raman spectroscopy was used to identify changes in the HDRM surface chemistry following exposure to the test solutions. AFM revealed that prolonged exposure led to pit formation and a subsequent increase in surface roughness, from 302.02 ± 30.20 to 430.59 ± 15.07 nm Ra, following a 24 h exposure. Young's modulus values decreased from 9.3 ± 7.0 to 0.53 ± 0.26 GPa under the same conditions, demonstrating a softening and embrittlement of the HDRM sample. Raman results revealed that immersion in the carbonated soft drink or acidic solution changed the nature of the HDRM structure, converting the HDRM surface chemistry from primarily hydrophobic to hydrophilic. Our study indicates that sustainability and durability of Rebaron HDRM are significantly reduced by prolonged exposure to carbonated (acidic) soft drink, resulting in deformation and degradation of the material surface.
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"Real-world" data on the nationwide epidemiology and treatment patterns of multiple sclerosis (MS) is very scarce in Asia. This study is aim to evaluate the 10-years trends in epidemiology and treatment patterns of MS with Taiwan's National Health Insurance Database (NHIRD). Patients aged 20 years or older and were newly diagnosed with MS between 2007 and 2016 were identified. The crude incidences of MS were presented annually and stratified by sex and age. Baseline characteristics and treatment patterns, particularly disease-modifying drugs (DMDs), were also analyzed. This study included 555 MS patients (mean age was 36.9 and 74.4% were female). The crude incidence rate of MS decreased slightly from 0.43 per 100,000 persons in 2007 to 0.24 per 100,000 persons in 2015. The female to male ratios remained mainly between 2 to 3. Approximately 80% of MS patients received initial DMDs, with interferon ß-1a as the dominant one. Furthermore, 37.5% of MS patients received subsequent DMDs, with fingolimod being the most frequently used. The median times from diagnosis to initial and to subsequent DMDs were 77 and 1239 days, respectively. This nationwide study provides up-to-date and sophisticated estimates of MS epidemiology and treatment pattern in "real-world" setting in Taiwan.
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Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/terapia , Adulto , Estudios de Cohortes , Femenino , Humanos , Incidencia , Interferón beta/uso terapéutico , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Taiwán/epidemiología , Adulto JovenRESUMEN
Arterial stiffness has been found to be a predictive risk factor for cardiovascular disease. Simple renal cysts are associated with prehypertension, hypertension, diabetes, and increased serum creatinine, which are risk factors of cardiovascular events. The aim of this work was to clarify the association between simple renal cysts and arterial stiffness defined by the brachial and ankle pulse wave velocity (baPWV). Subjects with and without simple renal cysts had right baPWV values of 1522.8 ± 357.5 cm/s and 1344.2 ± 268.8 cm/s, respectively (p < 0.001). Based on multiple linear regression analysis, the presence of simple renal cysts was associated with increased baPWV values (p < 0.001). Both the size and the number of simple renal cysts were positively associated with an increased baPWV value. Subjects with a cyst size ≥2 cm (p < 0.001) and a cyst number ≥2 (p < 0.01) had higher baPWV values than those without SRCs. Simple renal cysts are associated with increased arterial stiffness.
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Arteria Braquial/fisiopatología , Quistes/fisiopatología , Enfermedades Renales/fisiopatología , Rigidez Vascular/fisiología , Adulto , Anciano , Índice Tobillo Braquial , Pueblo Asiatico , Presión Sanguínea/fisiología , Quistes/diagnóstico por imagen , Femenino , Humanos , Hipertensión/fisiopatología , Enfermedades Renales/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Análisis de la Onda del Pulso , Factores de Riesgo , TaiwánRESUMEN
AIMS: Our study aimed to investigate the influence of different glycemic statuses and their fasting plasma glucose/2-hour post-load glucose on uric acid level. METHODS: A total of 14,787 subjects were recruited after excluding subjects with medication for hyperuricemia or diabetes. Fasting plasma glucose (FPG), 2-hour post-load glucose (2hPG), and uric acid (UA) were measured. Then, subjects were divided into normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes. RESULTS: After adjustment for clinical variables, in NGT group, there was no significant relationship found between UA level and FPG. However, there was a positive association between UA level and 2hPG (ßâ¯=â¯0.003, 95% CI: 0.002~0.004). A similar trend was also observed between UA level and 2hPG in IFG group (ßâ¯=â¯0.004, 95% CI: 0.000~0.009) and IGT group (ßâ¯=â¯0.005, 95% CI: 0.002~0.008), but relationship between UA level and FPG remained insignificant. In diabetes group, UA level was negatively associated with both FPG (ßâ¯=â¯-0.008, 95% CI: -0.010 ~ -0.007) and 2hPG (ßâ¯=â¯-0.005, 95% CI: -0.006 ~-0.003). CONCLUSIONS: In non-diabetic individuals, UA level increased with 2hPG, but not with FPG, and UA level was inversely associated with both FPG and 2hPG in diabetic population.
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Glucemia/análisis , Diabetes Mellitus Tipo 2/sangre , Ácido Úrico/sangre , Adulto , Anciano , Presión Sanguínea , Índice de Masa Corporal , Ayuno , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Factores Sexuales , TaiwánRESUMEN
BACKGROUND: There is growing evidence that pulmonary function impairment is related to cardiovascular events and death. Some studies have shown that the level of FVC is negatively related to arterial stiffness, but most studies were confined to men, and none of them examined the association of the presence of restrictive spirometry pattern with arterial stiffness. Therefore, this study aimed to investigate the association of restrictive spirometry pattern with arterial stiffness by sex. METHODS: This study recruited 2,961 subjects after excluding those with (1) obstructive lung disease, as defined by history and pulmonary function test; (2) history of asthma, lung cancer, tuberculosis, coronary heart disease, stroke, or any pulmonary structural deformities; and (3) medications influencing BP, plasma glucose, lipid profile, and pulmonary function test. Restrictive spirometry pattern was diagnosed as an FVC < 80% of the predicted value and an FEV1/FVC ratio ≥ 70%. Increased arterial stiffness was defined as right brachial ankle pulse wave velocity (baPWV) ≥ 1,400 cm/s. RESULTS: In both men and women, FVC was negatively associated with the baPWV level. Restrictive spirometry pattern was positively associated with increased arterial stiffness in both men and women (men: OR, 2.16; 95% CI, 1.33-3.50; women: OR, 1.95; 95% CI, 1.02-3.72) after adjustment for other clinical variables. CONCLUSIONS: Both restrictive spirometry pattern and reduced FVC were associated with a higher risk of arterial stiffness, not only in men but also in women. Clinically, assessment of arterial stiffness might be considered in individuals with restrictive spirometry pattern.
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Pulmón/fisiología , Rigidez Vascular/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/fisiopatología , Glucemia/metabolismo , Presión Sanguínea/fisiología , Colesterol/metabolismo , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Masculino , Persona de Mediana Edad , Caracteres Sexuales , Fumar/fisiopatología , Triglicéridos/metabolismo , Capacidad Vital/fisiología , Adulto JovenRESUMEN
OBJECTIVE: To examine the intention to quit waterpipe smoking among college students. PARTICIPANTS: A total of 276 University of Houston students identified through an online survey administered in February 2011. Participants indicated they had smoked a waterpipe in the month prior to the survey. METHODS: Cross-sectional study. Questions included demographics, tobacco use, perceived risk of waterpipe smoking, and social acceptability. Multivariate logistic regression was used to determine predictors of an intention to quit. RESULTS: Most of the sample participants (n = 227; 83%) reported that they had no intention to quit. Students believing that waterpipe smoking was harmful were more likely to have an intention to quit (odd ratio [OR] = 2.38, 95% confidence interval [CI; 1.05, 5.36]). Those who smoked for more than 60 minutes were less likely to have a desire to quit (OR = 0.29, 95% CI [0.12, 0.73]). CONCLUSIONS: The low level of a desire to quit demonstrated underscores the urgent need to develop interventions that educate users about expected harms of continued use.
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Asunción de Riesgos , Fumar/epidemiología , Estudiantes/psicología , Universidades/estadística & datos numéricos , Adulto , Intervalos de Confianza , Estudios Transversales , Femenino , Conocimientos, Actitudes y Práctica en Salud , Encuestas Epidemiológicas , Humanos , Masculino , Oportunidad Relativa , Salud Pública , Factores de Riesgo , Fumar/psicología , Estudiantes/estadística & datos numéricos , Estados Unidos/epidemiología , Adulto JovenRESUMEN
CONTEXT: KISS1 is a candidate gene for GnRH deficiency. OBJECTIVE: Our objective was to identify deleterious mutations in KISS1. PATIENTS AND METHODS: DNA sequencing and assessment of the effects of rare sequence variants (RSV) were conducted in 1025 probands with GnRH-deficient conditions. RESULTS: Fifteen probands harbored 10 heterozygous RSV in KISS1 seen in less than 1% of control subjects. Of the variants that reside within the mature kisspeptin peptide, p.F117L (but not p.S77I, p.Q82K, p.H90D, or p.P110T) reduces inositol phosphate generation. Of the variants that lie within the coding region but outside the mature peptide, p.G35S and p.C53R (but not p.A129V) are predicted in silico to be deleterious. Of the variants that lie outside the coding region, one (g.1-3659CâT) impairs transcription in vitro, and another (c.1-7CâT) lies within the consensus Kozak sequence. Of five probands tested, four had abnormal baseline LH pulse patterns. In mice, testosterone decreases with heterozygous loss of Kiss1 and Kiss1r alleles (wild-type, 274 ± 99, to double heterozygotes, 69 ± 16 ng/dl; r(2) = 0.13; P = 0.03). Kiss1/Kiss1r double-heterozygote males have shorter anogenital distances (13.0 ± 0.2 vs. 15.6 ± 0.2 mm at P34, P < 0.001), females have longer estrous cycles (7.4 ± 0.2 vs. 5.6 ± 0.2 d, P < 0.01), and mating pairs have decreased litter frequency (0.59 ± 0.09 vs. 0.71 ± 0.06 litters/month, P < 0.04) and size (3.5 ± 0.2 vs. 5.4 ± 0.3 pups/litter, P < 0.001) compared with wild-type mice. CONCLUSIONS: Deleterious, heterozygous RSV in KISS1 exist at a low frequency in GnRH-deficient patients as well as in the general population in presumably normal individuals. As in Kiss1(+/-)/Kiss1r(+/-) mice, heterozygous KISS1 variants in humans may work with other genetic and/or environmental factors to cause abnormal reproductive function.