Retrograde ejaculation (RE) has been reported in humans and animals but RE with subsequent sperm calculi has rarely been reported. This report documents clinical and pathological findings of spontaneous sperm cystolithiasis in four rhesus macaques. While this condition has been associated with repeated electroejaculation, spontaneous sperm cystolithiasis is highly unusual. The animals presented with either stranguria, dysuria, hematuria, distended abdomen or lethargy. Ultrasound examination revealed several hyperechoic masses within the lumen of the urinary bladder. The animals were euthanized due to poor prognosis or study end points. Postmortem examination revealed multiple angular, amorphous, soft to firm, pale yellow to greenish-brown and variably sized calculi in the lumen of the urinary bladder or prostatic/penile urethra. Histologically, the calculi were composed of numerous sperm embedded in abundant brightly eosinophilic matrix. Based on gross and histologic findings, RE associated sperm cystolithiasis was diagnosed, with ulcerative urethritis as the major primary apparent etiology. To the authors' knowledge, this is the first report of four spontaneous cases of sperm cystolithiasis in rhesus macaques.
by
Michael A. Pulsipher;
Brent R. Logan;
Deidre M. Kiefer;
Pintip Chitphakdithai;
Marcie L. Riches;
J. Douglas Rizzo;
Paolo Anderlini;
Susan F. Leitman;
James W. Varni;
Ann Haight
Although donation of bone marrow (BM)or peripheral blood stem cells (PBSCs)from children to family members undergoing allogeneic transplantation are well-established procedures, studies detailing levels of pain, symptoms, and long-term recovery are lacking. To address this lack, we prospectively enrolled 294 donors age <18 years at 25 pediatric transplantation centers in North America, assessing them predonation, peridonation, and at 1 month, 6 months, and 1 year postdonation. We noted that 71% of children reported pain and 59% reported other symptoms peridonation, with resolution to 14% and 12% at 1 month postdonation. Both older age (age 13 to 17 years versus younger)and female sex were associated with higher levels of pain peridonation, with the highest rates in older females (57% with grade 2-4 pain and 17% with grade 3-4 pain).
Multivariate analyses showed a 4-fold increase in risk for older females compared with males age <13 years (P <.001). At 1 year, 11% of 13- to 17-year-old females reported grade 2-4 pain, compared with 3% of males age 13 to 17 years, 0% of females age <13 years, and 1% of males age <13 years (P =.01). Males and females age 13 to 17 years failed to return to predonation pain levels at 1 year 22% and 23% of the time, respectively, compared with 3% and 10% in males and females age <13 years (P =.002). Our data show that females age 13 to 17 years are at increased risk of grade 2-4 pain at 1 year and >20% of females and males age 13 to 17 years do not return to baseline pain levels by 1 year after BM donation. Studies aimed at decreasing symptoms and improving recovery in older children are warranted.
Two urea transporters, UT-A1 and UT-A3, are expressed in the kidney terminal inner medullary collecting duct (IMCD) and are important for the production of concentrated urine. UT-A1, as the largest isoform of all UT-A urea transporters, has gained much attention and been extensively studied; however, the role and the regulation of UT-A3 are less explored. In this study, we investigated UT-A3 regulation by glycosylation modification. A site-directed mutagenesis verified a single glycosylation site in UT-A3 at Asn279. Loss of the glycosylation reduced forskolin-stimulated UT-A3 cell membrane expression and urea transport activity. UT-A3 has two glycosylation forms, 45 and 65 kDa. Using sugar-specific binding lectins, the UT-A3 glycosylation profile was examined. The 45-kDa form was pulled down by lectin concanavalin A (Con A) and Galant husnivalis lectin (GNL), indicating an immature glycan with a high amount of mannose (Man), whereas the 65-kDa form is a mature glycan composed of acetylglucosamine (GlcNAc) and poly-N-acetyllactosame (poly-LacNAc) that was pulled down by wheat germ agglutinin (WGA) and tomato lectin, respectively. Interestingly, the mature form of UT-A3 glycan contains significant amounts of sialic acid. We explored the enzymes responsible for directing UT-A3 sialylation. Sialyltransferase ST6GalI, but not ST3GalIV, catabolizes UT-A3 α2,6-sialylation. Activation of protein kinase C (PKC) by PDB treatment promoted UT-A3 glycan sialylation and membrane surface expression. The PKC inhibitor chelerythrine blocks ST6GalI-induced UT-A3 sialylation. Increased sialylation by ST6GalI increased UT-A3 protein stability and urea transport activity. Collectively, our study reveals a novel mechanism of UT-A3 regulation by ST6GalI-mediated sialylation modification that may play an important role in kidney urea reabsorption and the urinary concentrating mechanism.
We evaluated the relationship between estimated 24-hour urinary sodium excretion from the Kawasaki, Tanaka, and INTERSALT (International Study of Sodium, Potassium, and Blood Pressure) formulas and blood pressure (BP). We pooled 10 034 person-visit data from 3 cohort studies in Bangladesh that had measured 24-hour urine sodium (m-24hUNa), potassium, creatinine excretion, and BP. We used m-24hUNa, potassium, and creatinine where necessary, rather than spot urine values in the formulas. Bland-Altman plots were used to determine the bias associated with formula-estimated sodium relative to m-24hUNa. We compared the sodium excretion and BP relationships from m-24hUNa versus formula-estimated sodium excretions, using restricted cubic spline plots for adjusted multilevel linear models. All formulas overestimated 24-hour sodium at lower levels but underestimated 24-hour sodium at higher levels. There was a linear relationship between m-24hUNa excretion and systolic BP, while estimated sodium excretion from all 3 formulas had a J-shaped relationship with systolic BP. The relationships between urine sodium excretion and diastolic BP were more complex but were also altered by using formulas. All formulas had associations with BP when a sex-specific constant sodium concentration was inserted in place of measured sodium. Since we used the m-24hUNa, potassium, and creatinine concentrations in formulas, the J-shaped relationships are due to intrinsic problems in the formulas, not due to spot urine sampling. Formula-estimated 24-hour urine sodium excretion should not be used to examine the relationship between sodium excretion and BP since they alter the real associations.
Water bodies that serve as sources of drinking or recreational water are routinely monitored for fecal indicator bacteria (FIB) by state and local agencies. Exceedances of monitoring thresholds set by those agencies signal likely elevated human health risk from exposure, but FIB give little information about the potential source of contamination. To improve our understanding of how within-day variation could impact monitoring data interpretation, we conducted a study at two sites along the Chattahoochee River that varied in their recreational usage and adjacent land-use (natural versus urban), collecting samples every 30 min over one 24-h period. We assayed for three types of microbial indicators: FIB (total coliforms and Escherichia coli); human fecal-associated microbial source tracking (MST) markers (crAssphage and HF183/BacR287); and a suite of clinically relevant antibiotic resistance genes (ARGs; blaCTX-M, blaCMY, MCR, KPC, VIM, NDM) and a gene associated with antibiotic resistance (intl1). Mean levels of FIB and clinically relevant ARGs (blaCMY and KPC) were similar across sites, while MST markers and intI1 occurred at higher mean levels at the natural site. The human-associated MST markers positively correlated with antibiotic resistant-associated genes at both sites, but no consistent associations were detected between culturable FIB and any molecular markers. For all microbial indicators, generalized additive mixed models were used to examine diurnal variability and whether this variability was associated with environmental factors (water temperature, turbidity, pH, and sunlight). We found that FIB peaked during morning and early afternoon hours and were not associated with environmental factors. With the exception of HF183/BacR287 at the urban site, molecular MST markers and intI1 exhibited diurnal variability, and water temperature, pH, and turbidity were significantly associated with this variability. For blaCMY and KPC, diurnal variability was present but was not correlated with environmental factors. These results suggest that differences in land use (natural or urban) both adjacent and upstream may impact overall levels of microbial contamination. Monitoring agencies should consider matching sample collection times with peak levels of target microbial indicators, which would be in the morning or early afternoon for the fecal associated indicators. Measuring multiple microbial indicators can lead to clearer interpretations of human health risk associated with exposure to contaminated water.
Efforts to reduce the health and ecological burdens of household biomass combustion are underway in Ghana, principally by promoting clean cookstoves and fuels. Recent studies have focused on the sustained use of clean cookstoves, but sometimes household adopt a new cookstove and then end use of that stove. In this study, we introduce a novel framework for understanding and encouraging household transitions to cleaner cooking: clean fuel discontinuance. We leveraged data from the Ghana Randomized Air Pollution and Health Study (GRAPHS)(N = 1412) where pregnant women received either improved biomass (BioLite) or dual burner LPG stoves for free. LPG users were given free LPG refills during GRAPHS. Weekly questionnaires were administered. Stove use monitors tracked a sub-cohort (n = 220) 6 months before and after the fuel subsidy. We examined social and ecological determinants of stove use and discontinuance. Overall intervention stove use adherence was high throughout GRAPHS, with self-reported use at 69% and 86% of participant-weeks for BioLite and LPG arms respectively. Participants used intervention stoves less for meals requiring vigorous stirring. Burns from intervention stoves decreased use among BioLite (RR: 0.96, p = 0.009), but not LPG users. Device breakage was mentioned as an impediment in 18% of free-text responses for LPG users and 1% for BioLite. Tree canopy within a spatial buffer—a plausible proxy for biomass fuels access—was the only variable explaining LPG discontinued stove use in adjusted Cox time-to-event analyses (HR = −0.56, p < 0.001). Future studies should consider the stove use discontinuance framework.
The kidney is a main site of erythropoietin production in the body. We developed a new method for the detection of Epo protein by deglycosylation-coupled Western blotting. Detection of deglycosylated Epo enables the examination of small changes in Epo production. Using this method, we investigated the effects of angiotensin II (ATII) on Epo production in the kidney. ATII stimulated the plasma Epo concentration; Epo, HIF2α, and PHD2 mRNA expression in nephron segments in the renal cortex and outer medulla; and Epo protein expression in the renal cortex. In situ hybridization and immunohistochemistry revealed that ATII stimulates Epo mRNA and protein expression not only in proximal tubules but also in collecting ducts, especially in intercalated cells. These data support the regulation of Epo production in the kidney by the renin–angiotensin– aldosterone system (RAS).
Cognitive neuroscience seeks to discover the biological foundations of the human mind. One goal is to explain how mental operations are generated by the information processing architecture of the human brain. Our aim is to assess whether this is a well-defined objective. Our contention will be that it is not because the information processing of any given individual is not contained entirely within that individual’s brain. Rather, it typically includes components situated in the heads of others, in addition to being distributed across parts of the individual’s body and physical environment. Our focus here will be on cognition distributed across individuals, or on what we call the “community of knowledge,” the challenge that poses for reduction of cognition to neurobiology and the contribution of cognitive neuroscience to the study of communal processes.
Background: We compared the relationship between sodium (Na) intake and blood pressure when Na intake was estimated from first- and second-morning spot urine samples using the INTERSALT (International Study on Salt and Blood Pressure) formula, versus directly measured 24-hour samples. Methods and Results: We collected 24-hour urine and first- and second-morning voids of 383 participants in coastal Bangladesh for 2 visits. We measured participants’ blood pressure using an Omron® HEM–907 monitor. To assess the shape of the relationship between urinary Na and blood pressure, we created restricted cubic spline plots adjusted for age, sex, body mass index, smoking and alcohol consumption, physical activities, religion, sleep hours, and household wealth. To assess multicollinearity, we reported variance inflation factors, tolerances, and Leamer's and Klein's statistics following linear regression models. The mean daily urinary Na was 122 (SD 26) mmol/d for the first; 122 (SD 27) mmol/d for the second; and 134 (SD 70) mmol/d for the 24-hour samples. The restricted cubic spline plots illustrated no association between first-morning urinary Na and systolic blood pressure until the 90th percentile distribution followed by a downward relationship; a nonlinear inverse-V-shaped relationship between second-morning urinary Na and systolic blood pressure; and a monotonic upward relationship between 24-hour urinary Na and systolic blood pressure. We found no evidence of multicollinearity for the 24-hour urinary Na model. Conclusions: The urinary Na and systolic blood pressure relationship varied for 3 urinary Na measurements. Twenty-four-hour urinary Na captured more variability of Na intake compared with spot urine samples, and its regression models were not affected by multicollinearity.