Decline In Adults Research Articles

The Association between Obesity Phenotypes and Early Renal Function Decline in Adults without Hypertension, Dyslipidemia, and Diabetes.

BackgroundThe prevalence of chronic kidney disease is increasing worldwide. Several studies have suggested that obesity is associated with early renal dysfunction. However, little is known about the relationship between obesity phenotypes and early renal function decline. Therefore, this study aimed to identify the relationship between obesity phenotypes and early renal function decline in adults without hypertension, dyslipidemia, and diabetes.MethodsWe conducted a cross-sectional analysis of clinical and anthropometric data from 1,219 patients who underwent a routine health checkup in 2014. We excluded adults with cardiovascular disease, renal disease, diabetes, hypertension, dyslipidemia, or low glomerular filtration rate (<60 mL/min/1.73 m2). Renal function was determined according to the estimated glomerular filtration rate calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation.ResultsAge, sex, body mass index, waist circumference, triglyceride, low-density lipoprotein, and fasting glucose had an association with the estimated glomerular filtration rate. After adjusting for age, sex, smoking status, and alcohol intake, the odds ratios of the metabolically abnormal normal weight and metabolically abnormal obese phenotypes for the presence of low estimated glomerular filtration rates were 1.807 (95% confidence interval, 1.009– 3.236) and 1.834 (95% confidence interval, 1.162–2.895), compared with the metabolically healthy normal weight phenotype. However, the metabolically healthy obese phenotype did not show a significant association with early renal function decline.ConclusionIn this cross-sectional study, we confirmed the association between the metabolically abnormal normal weight and metabolically abnormal obese phenotypes and early kidney function decline in adults without hypertension, dyslipidemia, and diabetes.

Association between hippocampal dose and memory in survivors of childhood or adolescent low-grade glioma: a 10-year neurocognitive longitudinal study.

BackgroundHippocampal avoidance has been suggested as a strategy to reduce short-term memory decline in adults receiving whole-brain radiation therapy (RT). The purpose of this study was to determine whether the hippocampal dose in children and adolescents undergoing RT for low-grade glioma was associated with memory, as measured by verbal recall.MethodsEighty patients aged at least 6 years but less than 21 years with low-grade glioma were treated with RT to 54 Gy on a phase II protocol. Patients underwent age-appropriate cognitive testing at baseline, 6 months posttreatment, yearly through 5 years posttreatment, year 7 or 8, and year 10 posttreatment. Random coefficient models were used to estimate the longitudinal trends in cognitive assessment scores.ResultsMedian neurocognitive follow-up was 9.8 years. There was a significant decline in short-delay recall (slope = −0.01 standard deviation [SD]/year, P < 0.001), total recall (slope = −0.09 SD/y, P = 0.005), and long-delay recall (slope = −0.01 SD/y, P = 0.002). On multivariate regression, after accounting for hydrocephalus, decline in short-delay recall was associated with the volume of right (slope = −0.001 SD/y, P = 0.019) or left hippocampus (slope = −0.001 SD/y, P = 0.025) receiving 40 Gy (V40 Gy). On univariate regression, decline in total recall was only associated with right hippocampal dosimetry (V40 Gy slope = −0.002, P = 0.025). In children <12 years, on univariate regression, decline in long-delay recall was only associated with right (V40 Gy slope = −0.002, P = 0.013) and left (V40 Gy slope = −0.002, P = 0.014) hippocampal dosimetry.ConclusionIn this 10-year longitudinal study, greater hippocampal dose was associated with a greater decline in delayed recall. Such findings might be informative for radiation therapy planning, warranting prospective evaluation.

Population Pharmacokinetic Analyses and Model Validation of Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease.

Tolvaptan is the first approved drug treatment to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD). The objective is to develop (1091 subjects, 7335 observations) and validate (678 subjects, 3012 observations) a population pharmacokinetic model to describe tolvaptan pharmacokinetics in ADPKD subjects. The final model was evaluated with a bootstrapping method. The final model was internally and externally evaluated using visual predictive checks (VPC). Pharmacokinetics was best described by a 1‐compartmental model with 0‐order absorption, nonlinear relative bioavailability (F1), and first‐order elimination. Accounting for changes in F1 significantly improved the model: as the dose increased from 15 mg to 120 mg, F1 decreased by 36%. Population estimates for clearance/F (CL/F), volume of distribution/F (Vd/F), duration of absorption (D1), the highest dose at which F1 is lowest, and the amount of dose at which F1 is 50% were 12.6 L·h‐1, 110 L, 0.58 hour, 182 mg, and 166 mg, respectively. The interindividual variability was 64% in CL/F, 70% in Vd/F, and 238% in D1. Residual variability was described by a combined‐error model. The VPC (500 data sets simulated) showed that 76% to 92% of the observed data fell within the 90% prediction intervals. The model stability assessed by a 1000‐run bootstrap analysis showed that the mean parameter estimates of data were within 10% of those obtained with the final model. The developed model is robust and stable. Internal and external validation confirmed the model ability to describe the data optimally.

Predictors of accelerated FEV1 decline in adults with airflow limitation-Findings from the Health2006 cohort.

To investigate predictors of accelerated decline in forced expiratory volume in 1 s (FEV1) in individuals with preexisting airflow limitation (AL). Participants in the Health2006 baseline study aged ≥ 35 with FEV1/ forced vital capacity (FVC) < lower limit of normal (LLN) were invited for a 10-year follow-up. At both examinations, data were obtained on demographics, spirometry, fitness level, allergy, and exhaled nitric oxide. We used multiple regression modeling to predict the annual decline in FEV1, reported as regression coefficients (R) and 95% confidence intervals (CIs). A total of 123 (43% of those invited) participated in the follow-up examination, where more had exercise-induced dyspnea but fewer had asthma symptoms. Being female (R = −29.8 ml, CI: −39.7 to −19.8), diagnosed with asthma (R = −13.7, CI: −20.4 to −7.0) or atopic dermatitis (R = −29.0, CI: −39.7 to −18.4), and having current asthma symptoms or nightly respiratory symptoms (R = −22.1, CI: −31.9 to −12.4 and R = −14.3, CI: −19.9 to −8.7, respectively) were significantly associated with a steeper decline in FEV1. Although to a smaller extent, a steeper decline was also predicted by age, baseline FEV1, waist/hip-ratio, and number of pack-years smoked. In individuals with preexisting AL, being female and having ever or current respiratory symptoms were associated with an accelerated annual decline in FEV1.

MHA Ranks States on Prevalence of MH Disorders, Access to Care

MHA Ranks States on Prevalence of MH Disorders, Access to Care

Nomograms to predict naming decline after temporal lobe surgery in adults with epilepsy.

To develop and externally validate models to predict the probability of postoperative naming decline in adults following temporal lobe epilepsy surgery using easily accessible preoperative clinical predictors. In this retrospective, prediction model development study, multivariable models were developed in a cohort of 719 patients who underwent temporal lobe epilepsy surgery at Cleveland Clinic and externally validated in a cohort of 138 patients who underwent temporal lobe surgery at one of 3 epilepsy surgery centers in the United States (Columbia University Medical Center, Emory University School of Medicine, University of Washington School of Medicine). The development cohort was 54% female with an average age at surgery of 36 years (SD 12). Twenty-six percent of this cohort experienced clinically relevant postoperative naming decline. The model included 5 variables: side of surgery, age at epilepsy onset, age at surgery, sex, and education. When applied to the external validation cohort, the model performed very well, with excellent calibration and a c statistic (reflecting discriminatory ability) of 0.81. A second model predicting moderate to severe postoperative naming decline included 3 variables: side of surgery, age at epilepsy onset, and preoperative naming score. This model generated a c statistic of 0.84 in the external validation cohort and showed good calibration. Externally validated nomograms are provided in 2 easy-to-use formats (paper version and online calculator) clinicians can use to estimate the probability of naming decline in patients considering epilepsy surgery for treatment of pharmacoresistant temporal lobe epilepsy.

Association of Lead Exposure on Cognitive Decline due to Mediation and Interaction with Uric Acid

BACKGROUND: Low-level cumulative lead exposure has been associated with cognitive decline in adults. Previous studies suggest that lead increases levels of the antioxidant uric acid and that uric acid may also predict changes in cognitive function. We explored whether uric acid mediated or interacted with lead in the association between lead exposure and cognitive decline.METHODS: From 1991 to 2002, a subset of the Normative Aging Study cohort of community-dwelling men was assessed for cumulative lead exposure in the tibia and patella bones. The Mini-Mental State Examination (MMSE) was administered as a test of global cognition starting in 1992. We conducted formal mediation analysis using the first bone lead measurement, uric acid concurrent with baseline MMSE, and the difference between the second and baseline MMSE scores, adjusted for age at baseline MMSE, education, serum creatinine, smoking status and pack-years, drinking status, and years between the two MMSE tests.RESULTS: 552 men [mean (standard deviation) age: 67.27 (6.52)] took two MMSE tests that were 3.92 (1.80) years apart and had valid bone lead measurements. The total change in MMSE score for an interquartile range (20 µg/g) increase in patella lead was -0.29 (95% confidence interval: -0.49, -0.08) (p&amp;#61;0.007), due mostly to the direct association with lead [-0.25 (-0.44, -0.06) (p&amp;#61;0.01)] when uric acid was set to the mean value; the component due to interaction only was -0.03 (-0.07, 0.004) (p&amp;#61;0.08), due to mediation and interaction was 0.02 (-0.001, 0.05) (p&amp;#61;0.06), and due to mediation only was -0.03 (-0.07, 0.01) (p&amp;#61;0.20). Results with tibia lead were less robust.CONCLUSIONS: Prior studies have indicated significant effects of patella lead on cognitive decline, but accounting for uric acid may be needed to understand the full association between lead and cognitive decline.

A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan.

In the past, the treatment of autosomal dominant polycystic kidney disease (ADPKD) has been limited to the management of its symptoms and complications. Recently, the US Food and Drug Administration (FDA) approved tolvaptan as the first drug treatment to slow kidney function decline in adults at risk of rapidly progressing ADPKD. Full prescribing information approved by the FDA provides helpful guidelines but does not address practical questions that are being raised by nephrologists, internists, and general practitioners taking care of patients with ADPKD, and by the patients themselves. In this review, we provide practical guidance and discuss steps that require consideration before and after prescribing tolvaptan to patients with ADPKD to ensure that this treatment is implemented safely and effectively. These steps include confirmation of diagnosis; identification of rapidly progressive disease; implementation of basic renal protective measures; counseling of patients on potential benefits and harms; exclusions to use; education of patients on aquaresis and its expected consequences; initiation, titration, and optimization of tolvaptan treatment; prevention of aquaresis-related complications; evaluation and management of liver enzyme elevations; and monitoring of treatment efficacy. Our recommendations are made on the basis of published evidence and our collective experiences during the randomized, clinical trials and open-label extension studies of tolvaptan in ADPKD.

Cognitive Decline in Adults Aged 65 and Older in Cumbayá, Quito, Ecuador: Prevalence and Risk Factors.

ObjectiveTo assess the prevalence of and risk factors for cognitive decline and dementia in individuals greater than 65 years of age in Cumbayá, Quito, Ecuador.MethodsThis is a cross-sectional observational study that was carried out in adults over age 65. The Mini Mental State Examination (MMSE), Ascertain Dementia Eight-Item Informant Questionnaire (AD8), and Mini Nutritional Assessment (MNA) were used to assess the cognitive status and nutritional habits of this population.ResultsA total of 144 patients (mean age 75.3 years, 77.1% female) participated in this study. Forty percent of patients had AD8 and MMSE scores consistent with cognitive impairment and possible dementia. Age (p < 0.01), lower educational level (p < 0.01), history of stroke (p < 0.01), history of intracerebral hemorrhage (p < 0.01), diabetes mellitus (p < 0.01), and malnutrition (p < 0.01) were statistically significant risk factors for cognitive impairment. Exercise was found to be protective against cognitive decline in our study group (p < 0.03). Gender, ethnicity, location, head trauma, Parkinson disease, hypercholesterolemia, myocardial infarction, thyroid disease, depression, anxiety, and family history of dementia were not found to be associated with cognitive decline in this population.ConclusionsThe prevalence of cognitive impairment and possible dementia is 18–21% at age 65 and 54–60% at age 85 in Cumbayá, Quito, Ecuador. The major risk factors for cognitive impairment in this population are age, low educational level, malnutrition, prior stroke, prior intracerebral hemorrhage, and diabetes. Protective factors for cognitive decline include exercise and possibly modest consumption of alcohol.

Effect of Coaching to Increase Water Intake on Kidney Function Decline in Adults With Chronic Kidney Disease

In observational studies, increased water intake is associated with better kidney function. To determine the effect of coaching to increase water intake on kidney function in adults with chronic kidney disease. The CKD WIT (Chronic Kidney Disease Water Intake Trial) randomized clinical trial was conducted in 9 centers in Ontario, Canada, from 2013 until 2017 (last day of follow-up, May 25, 2017). Patients had stage 3 chronic kidney disease (estimated glomerular filtration rate [eGFR] 30-60 mL/min/1.73 m2 and microalbuminuria or macroalbuminuria) and a 24-hour urine volume of less than 3.0 L. Patients in the hydration group (n = 316) were coached to drink more water, and those in the control group (n = 315) were coached to maintain usual intake. The primary outcome was change in kidney function (eGFR from baseline to 12 months). Secondary outcomes included 1-year change in plasma copeptin concentration, creatinine clearance, 24-hour urine albumin, and patient-reported overall quality of health (0 [worst possible] to 10 [best possible]). Of 631 randomized patients (mean age, 65.0 years; men, 63.4%; mean eGFR, 43 mL/min/1.73 m2; median urine albumin, 123 mg/d), 12 died (hydration group [n = 5]; control group [n = 7]). Among 590 survivors with 1-year follow-up measurements (95% of 619), the mean change in 24-hour urine volume was 0.6 L per day higher in the hydration group (95% CI, 0.5 to 0.7; P < .001). The mean change in eGFR was -2.2 mL/min/1.73 m2 in the hydration group and -1.9 mL/min/1.73 m2 in the control group (adjusted between-group difference, -0.3 mL/min/1.73 m2 [95% CI, -1.8 to 1.2; P = .74]). The mean between-group differences (hydration vs control) in secondary outcomes were as follows: plasma copeptin, -2.2 pmol/L (95% CI, -3.9 to -0.5; P = .01); creatinine clearance, 3.6 mL/min/1.73 m2 (95% CI, 0.8 to 6.4; P = .01); urine albumin, 7 mg per day (95% CI, -4 to 51; P = .11); and quality of health, 0.2 points (95% CI, -0.3 to 0.3; P = .22). Among adults with chronic kidney disease, coaching to increase water intake compared with coaching to maintain the same water intake did not significantly slow the decline in kidney function after 1 year. However, the study may have been underpowered to detect a clinically important difference. clinicaltrials.gov Identifier: NCT01766687.

Use of statins and the risk of dementia and mild cognitive impairment: A systematic review and meta-analysis

We conducted a systematic review and meta-analysis to investigate whether the use of statins could be associated with the risk of all-caused dementia, Alzheimer’s disease (AD), vascular dementia (VaD), and mild cognitive impairment (MCI). Major electronic databases were searched until December 27th, 2017 for studies investigating use of statins and incident cognitive decline in adults. Random-effects meta-analyses calculating relative risks (RRs) were conducted to synthesize effect sizes of individual studies. Twenty-five studies met eligibility criteria. Use of statins was significantly associated with a reduced risk of all-caused dementia (k = 16 studies, adjusted RR (aRR) = 0.849, 95% CI = 0.787–0.916, p = 0.000), AD (k = 14, aRR = 0.719, 95% CI = 0.576–0.899, p = 0.004), and MCI (k = 6, aRR = 0.737, 95% CI = 0.556–0.976, p = 0.033), but no meaningful effects on incident VaD (k = 3, aRR = 1.012, 95% CI = 0.620–1.652, p = 0.961). Subgroup analysis suggested that hydrophilic statins were associated with reduced risk of all-caused dementia (aRR = 0.877; CI = 0.818–0.940; p = 0.000) and possibly lower AD risk (aRR = 0.619; CI = 0.383–1.000; p = 0.050). Lipophilic statins were associated with reduced risk of AD (aRR = 0.639; CI = 0.449–0.908; p = 0.013) but not all-caused dementia (aRR = 0.738; CI = 0.475–1.146; p = 0.176). In conclusion, our meta-analysis suggests that the use of statins may reduce the risk of all-type dementia, AD, and MCI, but not of incident VaD.

Association of cytomegalovirus and Epstein-Barr virus with cognitive functioning and risk of dementia in the general population: 11-year follow-up study

BackgroundEarlier studies have documented an association between cytomegalovirus and cognitive impairment, but results have been inconsistent. Few studies have investigated the association of cytomegalovirus and Epstein-Barr virus with cognitive decline longitudinally. Our aim was to examine whether cytomegalovirus and Epstein-Barr virus are associated with cognitive decline in adults. MethodThe study sample is from the Finnish Health 2000 Survey (BRIF8901, n = 7112), which is representative of the Finnish adult population. The sample was followed up after 11 years in the Health 2011 Survey. In addition, persons with dementia were identified from healthcare registers. ResultsIn the Finnish population aged 30 and over, the seroprevalence of cytomegalovirus was estimated to be 84% and the seroprevalence of Epstein-Barr virus 98%. Seropositivity of the viruses and antibody levels were mostly not associated with cognitive performance. In the middle-aged adult group, cytomegalovirus serointensity was associated with impaired performance in verbal learning. However, the association disappeared when corrected for multiple testing. No interactions between infection and time or between the two infections were significant when corrected for multiple testing. Seropositivity did not predict dementia diagnosis. ConclusionsThe results suggest that adult levels of antibodies to cytomegalovirus and Epstein-Barr virus may not be associated with a significant decline in cognitive function or with dementia at population level.

Shorter telomere length in cord blood associated with prenatal air pollution exposure: Benefits of intervention

BackgroundTo examine the molecular benefits of the government action to close the local coal burning power plant in Tongliang County, Chongqing Municipality, we compared biologic markers and health outcomes in two successive birth cohorts enrolled before and after the plant was shut down. In this city, polycyclic aromatic hydrocarbons (PAH) were primarily emitted by the coal burning facility. We previously reported that cord blood levels of PAH-DNA adducts (a biomarker of exposure) and various adverse health outcomes were reduced in the second cohort, whereas levels of brain-derived neurotrophic factor/BDNF (a protein involved in neuronal growth) were increased. Here we assessed telomere length (TL), which has been associated with risk of certain chronic diseases, early mortality, aging and cognitive decline in adults. ObjectivesThe goals of the present study were to determine whether TL differed between the two cohorts and whether prenatal PAH exposure, estimated by PAH-DNA adducts in cord white blood cells of newborns in China, were predictive of shorter TL in cord blood, suggesting the potential accrual of risk of certain chronic diseases during the prenatal period. We explored relationships of TL with BDNF and neurodevelopmental outcomes, each previously associated with PAH-DNA adducts in these cohorts, as well as the potential mediating role of TL in the associations between adducts and neurodevelopmental outcomes. MethodsWe analyzed TL in cord blood of 255 newborns who also had data on PAH-DNA adducts, BDNF, and relevant covariates. Multiple regression analysis was carried out to test associations between adducts and TL and between TL and BDNF, adjusting for relevant covariates. In the subset with developmental quotient (DQ) scores from Gesell testing at age 2 (N = 210), we explored whether TL was a mediator of the relationship between PAH-DNA adducts and DQ scores by first examining the associations between cord adducts and DQ, cord adducts and TL, and TL and DQ, adjusting for the same covariates. ResultsAs hypothesized, the mean TL was significantly higher in the second cohort compared to the first cohort. Overall, PAH-DNA cord adducts were significantly and inversely correlated with TL. Multiple regression analysis showed a significant association between adducts and TL, after adjusting for key covariates: β (effect size per standard deviation adducts) = −0.019, p = .003. The regression coefficient of TL on (Ln) BDNF was also significant (β = 0.167, p < .001). Exploratory analysis, regressing TL on Gesell developmental scores, showed generally inverse, but not significant associations. TL was not, therefore, deemed to be a potential mediator of the association between adducts and developmental scores at age two. ConclusionThis study provides the first evidence that prenatal PAH exposure from coal burning may adversely affect TL, with potential implications for future risk of chronic diseases including cardiovascular disease. The improvement in TL in the second cohort and the observed correlation between increased TL and higher levels of BDNF indicate direct benefits to the health and development of children resulting from the government's closure of the power plant.

Dietary antioxidants and 10-year lung function decline in adults from the ECRHS survey.

The relationship between lung function decline and dietary antioxidants over 10 years in adults from three European countries was investigated.In 2002, adults from three participating countries of the European Community Respiratory Health Survey (ECRHS) answered a questionnaire and underwent spirometry (forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)), which were repeated 10 years later. Dietary intake was estimated at baseline with food frequency questionnaires (FFQ). Associations between annual lung function decline (mL) and diet (tertiles) were examined with multivariable analyses. Simes’ procedure was applied to control for multiple testing.A total of 680 individuals (baseline mean age 43.8±6.6 years) were included. A per-tertile increase in apple and banana intake was associated with a 3.59 mL·year−1 (95% CI 0.40, 7.68) and 3.69 mL·year−1 (95% CI 0.25, 7.14) slower decline in FEV1 and FVC, respectively. Tomato intake was also associated with a slower decline in FVC (4.5 mL·year−1; 95% CI 1.28, 8.02). Only the association with tomato intake remained statistically significant after the Simes’ procedure was performed. Subgroup analyses showed that apple, banana and tomato intake were all associated with a slower decline in FVC in ex-smokers.Intake of fruits and tomatoes might delay lung function decline in adults, particularly in ex-smokers.

Size-conditional smolting and the response of Carmel River steelhead to two decades of conservation efforts.

Threshold effects are common in ecosystems and can generate counterintuitive outcomes in management interventions. A threshold effect proposed for steelhead trout (Oncorhynchus mykiss) is size-conditional smolting and marine survival. Steelhead are anadromous, maturing in the ocean but migrating to freshwater to spawn, where their offspring reside for one or more years before smolting—physiologically transforming to a saltwater form—and migrating to the ocean. In conditional smolting, juveniles transform only if growth exceeds a threshold body size prior to migration season, and subsequent marine survival correlates with size at ocean entry. Conditional smolting suggests that efforts to improve freshwater survival of juveniles may reduce smolt success if they increase competition and reduce growth. Using model-selection techniques, we asked if this effect explained declining numbers of adult Carmel River steelhead. This threatened population has been the focus of two decades of habitat restoration, as well as active translocation and captive-rearing of juveniles stranded in seasonally dewatered channels. In the top-ranked model selected by information-theoretic criteria, adult decline was linked to reduced juvenile growth rates in the lower river, consistent with the conditional smolting hypothesis. According to model inference, since 2005 most returning adult steelhead were captively-reared. However, a lower-ranked model without conditional smolting also had modest support, and suggested a negative effect of captive rearing. Translocations of juvenile fish to perennial reaches may have reduced the steelhead run slightly by raising competition, but this effect is confounded in the data with effects of river flow on growth. Efforts to recover Carmel River steelhead will probably be more successful if they focus on conditions promoting rapid growth in the river. Our analysis clearly favored a role for size-conditional smolting and marine survival in the decline of the population, but did not definitively rule out alternative explanations.

Age-related cognitive decline in adults with DM1: a 9-year longitudinal study

Age-related cognitive decline in adults with DM1: a 9-year longitudinal study

Spotlight on the October 24 issue

#### Notable in Neurology This issue features an article that investigates whether common genetic variants in familial cerebral small vessel disease confer risk of lacunar ischemic stroke and deep intracerebral hemorrhage and another that associates the synaptic protein neurogranin with age-related cognitive decline in adults without dementia. A featured article examines the effect of caffeine on objective motor scores in Parkinson disease. ### Brain network connectivity differs in early-onset neurodegenerative dementia![Graphic][1] Connectomics may aid clinical diagnosis of early-onset Alzheimer disease and behavioral variant frontotemporal dementia. The authors investigated functional brain network architecture to provide insight into disease-specific variations that could aid differential diagnosis in … [1]: /embed/inline-graphic-1.gif

The quantification of testicular cells during the postnatal development in two Caviomorph rodents: the guinea pig (Cavia porcellus) and the cutia (Dasyprocta agouti).

The germinative, Sertoli and Leydig cells of two caviomorph rodents (Cavia porcellus and Dasyprocta agouti) were counted as well as the estimation of the total volume of the testis and the total volume of seminiferous tubules and interstitium in prepubertal, pubertal and adult animals. The number of spermatogonia, spermatocytes and spermatids cells increased during the pubertal phase in both rodents, notably the spermatid cells. The spermatocyte and spermatid slightly decreased in the adult of both rodents, but the increment in spermatogonia cells number was seen, mainly in cutias. The number of Sertoli cells increased in pubertal rodents, but in the adult the number reduced. Substantial number of Leydig cells was counted in pubertal and adult guinea pigs. In cutias, the number of Leydig cells increased in pubertal phase and decline in adults. The design-based stereological method has proven to be unbiased and reliable to be applied in reproduction studies.

Trends in Invasive Pneumococcal Disease in Cancer Patients After the Introduction of 7-valent Pneumococcal Conjugate Vaccine: A 20-year Longitudinal Study at a Major Urban Cancer Center.

Rates of invasive pneumococcal disease (IPD) declined since routine childhood immunization with the 7-valent pneumococcal conjugate vaccine (PCV7) in 2000. We studied the impact of PCV7 on the incidence of IPD in cancer patients. This was a retrospective analysis of adult and pediatric patients treated at Memorial Sloan Kettering Cancer Center from 1992 to 2012. Recovery of Streptococcus pneumoniae from a sterile site defined IPD. IPD incidence was calculated as cases per 1,000 unique patient-visits per year (UPV). IPD incidence was calculated for the periods: "before PCV7" (1992-2000), "after PCV7" (2001-2010) and "after PCV13" (2011-2012). Of 343 IPD cases, 165, 155, and 23 cases occurred "before PCV7," "after PCV7" and "after PCV13" respectively. The IPD incidence declined from 0.43 "before PCV7" to 0.17 "after PCV7" (95% confidence interval [CI]: 0.33-0.46, P < .001) and 0.11 "after PCV13" (95% CI: 0.42-0.96, P = .004). Adults with hematologic malignancies and children had the highest incidence. In patients 1-4 years old, the incidence declined from 11.2 "before PCV7" to 2.38 "after PCV7" (79% decrease, 95% CI: 0.1-0.4, P < .001). In patients with hematologic malignancies, the incidence declined from 2.55 "before PCV7" to 0.92 "after PCV7" (64% decrease, 95% CI: 0.27-0.47, P < .001). The incidence of IPD among cancer patients sharply declined after introduction of PCV7; especially in high risk groups. The decline in adults suggests an indirect effect from PCV7 childhood vaccination.

Predictors of early renal function decline in adults with Type1 diabetes: the Coronary Artery Calcification in Type 1 Diabetes and the Pittsburgh Epidemiology of Diabetes Complications studies.

Diabetic kidney disease is one of the leading complications of Type1 diabetes, but its prediction remains a challenge. We examined predictors of rapid decline in estimated GFR (eGFR) in two Type1 diabetes cohorts: the Coronary Artery Calcification in Type 1 Diabetes (CACTI) and the Pittsburgh Epidemiology of Diabetes Complications (EDC). A select subset of participants (CACTI: n=210 and EDC: n=98) diagnosed before 17years of age with Type1 diabetes duration ≥7years, and follow-up data on eGFR by CKD-EPI creatinine for up to 8years were included in the analyses. Early renal function decline was defined as annual decline in eGFR ≥3ml/min/1.73m2 , and normal age-related decline as eGFR ≤1ml/min/1.73m2 . Parallel logistic regression models were constructed in the two cohorts. Early renal function decline incidence was 36% in CACTI and 41% in EDC. In both cohorts, greater baseline eGFR (CACTI: OR 3.12, 95% CI 1.97-5.05; EDC: OR 1.92, 95% CI 1.17-3.15 per 10ml/min/1.73m2 ) and log albumin-to-creatinine (ACR) (CACTI: OR 3.24, 95% CI 1.80-5.83; EDC: OR 1.87, 95% CI 1.18-2.96 per 1unit) predicted greater odds of early renal function decline in fully adjusted models. Conversely, ACE inhibition predicted lower odds of early renal function decline in women in CACTI, but similar relationships were not observed in women in EDC. A substantial proportion of people with Type1 diabetes in the EDC and CACTI cohorts experienced early renal function decline over time. ACE inhibition appeared to be protective only in women in CACTI where the prevalence of its use was twofold higher compared with the EDC.