Sperm velocity in seminal plasma and the association with gender of offspring

The gender of the offspring is determined by the fertilizing sperm. Previous gender studies were based on washed sperm, but not on sperm in seminal plasma. The objective was to correlate motility parameters assessed during semen analyses with the offspring gender. For comparison, fixed sperm head DNA quantitated by Hoechst 33342 fluorescence microscopy was also analyzed. Forty-six patients undergoing assisted reproduction procedures resulted in livebirth deliveries with either male or female-predominant offsprings. Sperm head fluorescence was weakly correlated to the gender in 61% of the cases. Sperm of patients with male offsprings had slower curvilinear (44.2 +/- 1.8 mean +/- SEM, versus, 49.9 +/- 2.7 micro /sec) and slower average path velocities (32.4 +/- 1.2 versus 36.3 +/- 1.7 micro /sec). Using cut-off values for the curvilinear (< 49 micro /sec) and average path (< 36 micro /sec) velocities of sperm swimming in seminal plasma, the two parameters predicted 75 and 68% of the male offspring births, respectively. The data suggest that sperm movement in seminal plasma is a marker for factors that skew the ratio of the X- to Y-sperm populations.     

Problem alcohol use in veterans with mild traumatic brain injury: Associations with cognitive performance and psychiatric symptoms

Introduction: Given that little is known about the associations between alcohol use, cognition, and psychiatric symptoms among veterans with a history of mild traumatic brain injury (mTBI), we aimed to (a) characterize how they differ from veteran controls on a measure of problem drinking; (b) investigate whether problem drinking is associated with demographic or mTBI characteristics; and (c) examine the associations between alcohol use, mTBI history, psychiatric functioning, and cognition. Method: We assessed 59 veterans (n = 32 with mTBI history; n = 27 military controls) for problem alcohol use (Alcohol Use Disorders Identification Test: AUDIT), psychiatric symptoms, and neuropsychological functioning. Results: Compared to controls, veterans with mTBI history were more likely to score above the AUDIT cutoff score of 8 (p = .016), suggesting a higher rate of problem drinking. Participants with mTBI history also showed elevated psychiatric symptoms (ps < .001) and lower cognitive scores (ps < .05 to < .001). Veterans with higher AUDIT scores were younger (p = .05) and had less education (p < .01) and more psychiatric symptoms (ps < .01), but mTBI characteristics did not differ. After controlling for combat and mTBI history (R² = .04, ns) and posttraumatic stress disorder (PTSD) symptoms (ΔR² = .08, p = .05), we found that higher AUDIT scores were associated with poorer attention/processing speed, F(9, 37) = 2.55, p = .022; ΔR² = .26, p = .03. Conclusions: This preliminary study suggested that veterans with mTBI history may be at increased risk for problem drinking. Problem alcohol use was primarily associated with more severe PTSD symptoms and poorer attention/processing speed, though not with combat or mTBI characteristics per se. Importantly, findings emphasize the importance of assessing for and treating problematic alcohol use and comorbid psychiatric symptoms among veterans, including those with a history of neurotrauma.     

Prevalence of conditions potentially associated with lower urinary tract symptoms in men

OBJECTIVE: To estimate the frequency of conditions associated with lower urinary tract symptoms (LUTS, typically included when assessing benign prostatic hyperplasia, BPH), as other causes of LUTS should be excluded when diagnosing BPH, using data from the Olmsted County Study of Urinary Symptoms and Health Status among Men. SUBJECTS AND METHODS: During 1989-91, Caucasian men aged 40-79 years were randomly selected from the Olmsted County population. Before contact, eligibility was determined by reviewing the community medical records. Baseline exclusion criteria included comorbid pre-existing conditions or treatments, e.g. prostate, bladder or lower back surgery, bladder neck contracture or cancer, diabetes with lower extremity amputation, and neurological diseases, including Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, tabes dorsalis and stroke. Men with these conditions were excluded from the Olmsted County Study at baseline, because these conditions are potentially associated with LUTS. RESULTS: Of the 5100 randomly sampled men, 13.4% met at least one of the pre-existing exclusion criteria. Individually, the frequency of exclusions was 7.8% for prostate cancer or surgery, 4.8% for back surgery, 1.3% for bladder surgery and 1.4% for neurological conditions. All other conditions represented <1.0% of the study exclusions. Older men were more likely to meet at least one of the exclusion criteria, with men in their fifth to eighth decade having a total exclusion frequency of 1.4%, 5.4%, 8.5% and 32.8%, respectively. The most common reason for men in their fifth decade to be excluded was lower back surgery (0.9%), whereas the most common reason in the eighth was prostate surgery (21.8%). CONCLUSIONS: In men, conditions that may contribute to LUTS, other than BPH, are prevalent in the community and increase in frequency with age. It is important that other conditions associated with LUTS be excluded before a definitive diagnosis of BPH. Any oversight in this initial evaluation can potentially result in misclassification bias, misdiagnosis and incorrect treatment of patients.     

Posttraumatic stress disorder and functional impairment among World Trade Center Health Registry enrollees 14–15 years after the September 11, 2001, terrorist attacks

The September 11, 2001, terrorist attacks on the World Trade Center (WTC) in New York City (9/11) had health-related consequences, including posttraumatic stress disorder (PTSD). PTSD is associated with functional impairment, which varies by symptom severity and other factors. This study aimed to identify predictors of functional impairment in individuals with low versus high PTSD symptom severity levels. WTC Health Registry enrollees exposed to 9/11 were surveyed four times between 2003 and 2015; cumulated data for individuals who endorsed at least one symptom on the PTSD Checklist–Civilian Version (PCL-C) at Wave 4 (2015–2016) were included (N = 30,287) and examined cross-sectionally. Individuals were classified based on PCL-C scores as having low/no (2–29) or high levels of PTSD symptom severity (≥ 44). Functional impairment was defined as subsequent difficulties in daily living. Among low/no PTSD severity participants, adjusted odds ratios (aORs) for the associations between functional impairment and poor self-rated health (vs. good), low social support (vs. high), and no physical activity (vs. active) were 1.23–1.92. In the same group, low versus high household income was associated with more functional impairment, aOR = 1.34, 95% CI [1.13, 1.59]. Among participants with high-level PTSD symptoms, women, aOR = 1.70, 95% CI [1.31, 2.20], and Hispanic enrollees, aOR = 1.76, 95% CI [1.31, 2.36], were more likely to report an absence of impairment. Self-rated health, social support, and physical activity emerged as important predictors of PTSD-related functional impairment across PTSD symptom severity levels, supporting clinical interventions targeting these factors.     

I-123 mIBG and Tc-99m myocardial SPECT imaging to predict inducibility of ventricular arrhythmia on electrophysiology testing: A retrospective analysis

Objectives

The purpose of this study is to assess mIBG uptake in scar border zone and its relation with ventricular arrhythmia (VA) inducibility on electrophysiology (EP) testing using I-123 mIBG SPECT and resting Tc-99m SPECT myocardial perfusion imaging (MPI).

Methods

Forty-seven patients from a previous clinical trial were retrospectively analyzed. These patients underwent I-123 mIBG and resting Tc-99m tetrofosmin SPECT, and EP testing. Twenty-eight patients were positive (EP+) and 19 patients were negative (EP?) for inducibility of sustained (>30 seconds) VA on EP testing. MPI scar extent, border zone extent, and mIBG uptake in border zone were used to predict VA inducibility on EP testing, respectively.

Results

There was no significant difference in scar extent between the EP+ and EP? groups. The EP+ group had significantly larger border zone and lower mIBG uptake ratio in the border zone than the EP? group. Receiver operating characteristic (ROC) curve analysis showed that the prediction accuracy for border zone extent (area under ROC = 0.75) was better than scar extent (area under ROC = 0.66). The prediction accuracy was further improved (area under ROC = 0.78), when assessing mIBG uptake in the border zone.

Conclusion

A new tool has been developed to measure scar and border zone and to assess mIBG uptake in scar and border zone from combined I-123 MIBG SPECT and resting Tc-99m SPECT MPI. The mIBG uptake in the border zone predicted VA inducibility on EP testing with a promising accuracy.     

Remodeling of murine intrasynovial tendon adhesions following injury: MMP and neotendon gene expression

Tendon injury frequently results in the formation of adhesions that reduce joint range of motion. To study the cellular, molecular, and biomechanical events involved in intrasynovial tendon healing and adhesion formation, we developed a murine flexor tendon healing model in which the flexor digitorum longus (FDL) tendon of C57BL/6 mice was transected and repaired using suture. This model was used to test the hypothesis that murine flexor tendons heal with differential expression of matrix metalloproteases (MMPs), resulting in the formation of scar tissue as well as the subsequent remodeling of scar and adhesions. Healing tendons were evaluated by histology, gene expression via real-time RT-PCR, and in situ hybridization, as well as biomechanical testing to assess the metatarsophalangeal (MTP) joint flexion range of motion (ROM) and the tensile failure properties. Tendons healed with a highly disorganized fibroblastic tissue response that was progressively remodeled through day 35 resulting in a more organized pattern of collagen fibers. Initial repair involved elevated levels of Mmp-9 at day 7, which is associated with catabolism of damaged collagen fibers. High levels of Col3 are consistent with scar tissue, and gradually transition to the expression of Col1. Scleraxis expression peaked at day 7, but the expression was limited to the original tendon adjacent to the injury site, and no expression was present in granulation tissue involved in the repair response. The MTP joint ROM with standardized force on the tendon was decreased on days 14 and 21 compared to day 0, indicating the presence of adhesions. Peak expressions of Mmp-2 and Mmp-14 were observed at day 21, associated with tendon remodeling. At day 28, two genes associated with neotendon formation, Smad8 and Gdf-5, were elevated and an improvement in MTP ROM occurred. Tensile strength of the tendon progressively increased, but by 63 days the repaired tendons had not reached the tensile strength of normal tendon. The murine model of primary tendon repair, described here, provides a novel mechanism to study the tendon healing process, and further enhances the understanding of this process at the molecular, cellular, and biomechanical level. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 833–840, 2009     

MR imaging of anterior cruciate ligament reconstruction graft

OBJECTIVE. The objective was to determine the MR imaging findings that differentiate intact anterior cruciate ligament reconstruction graft, partial-thickness tear, and full-thickness tear, using arthroscopy as the gold standard. MATERIALS AND METHODS. Sixteen consecutive MR imaging examinations were retrospectively and independently evaluated by two musculoskeletal radiologists for primary signs (graft signal, orientation, fiber continuity, complete discontinuity, and thickness) and secondary signs (anterior tibial translation, uncovered posterior horn lateral meniscus, posterior cruciate ligament hyperbuckling, and abnormal posterior cruciate ligament line) of anterior cruciate ligament reconstruction graft tear in 15 patients with follow-up arthroscopy. Results were compared with arthroscopy, and both receiver operating characteristic curves and kappa values for interobserver variability were calculated. RESULTS. Arthroscopy revealed four full-thickness graft tears, seven partial-thickness tears, and five intact grafts. Of the primary signs, graft fiber continuity in the coronal plane and 100% graft thickness in the sagittal or coronal plane were most valuable in excluding full-thickness tear. Complete discontinuous graft in the coronal plane also was valuable in diagnosis of full-thickness tear. Of the secondary signs, anterior tibial translation and uncovered posterior horn lateral meniscus assisted in differentiating graft tear (partial or full thickness) from intact graft. The other primary and secondary signs were less valuable. Kappa values were highest for graft fiber continuity and graft discontinuity in the coronal plane. CONCLUSION. Full-thickness anterior cruciate ligament graft tear can be differentiated from partial-thickness tear or intact graft by evaluating for graft fiber continuity (coronal plane), complete graft discontinuity (coronal plane), and graft thickness (coronal or sagittal plane).     

Presumed circle area ratio of the prostate in a community‐based group of men

OBJECTIVE

To determine the normal values for the presumed circle area ratio (PCAR) in a group of community‐based men, and to determine whether PCAR is associated with specific urological outcomes.

PATIENTS AND METHODS

The study was a cross‐sectional analysis among 328 Caucasian men (94% participation) residing in Olmsted County, Minnesota, USA. The PCAR was measured during prostatic ultrasonography. Lower urinary tract symptoms (LUTS) were measured using the American Urologic Association Symptom Index. The peak urinary flow rate was measured by a uroflowmeter, and the postvoid residual volume (PVR) was assessed using the BladderScan^TM BVM 6500 (Verathon, Bothell, WA, USA). Correlations between PCAR and presence of LUTS, peak urinary flow rate, and PVR were determined using Spearman correlation coefficients. Unadjusted and adjusted odds ratios (ORs) were calculated using logistic regression to determine the associations between PCAR thresholds and categorical urological outcomes.

RESULTS

The median (interquartile range) PCAR was 0.85 (0.81–0.88). After adjusting for age and total prostate volume, men who had PCARs of >0.90 were more likely to have elevated overall and obstructive symptom scores (OR 2.95, 95% confidence interval 1.39–6.25, and 3.47, 1.63–7.39, respectively).

CONCLUSION

PCAR might add further information beyond total prostate volume when predicting the development of obstructive LUTS.     

Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Background  

Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.     

Liver is the site of splanchnic cortisol production in obese nondiabetic humans

OBJECTIVE—To determine the contribution of liver and viscera to splanchnic cortisol production in humans.RESEARCH DESIGN AND METHODS—D4 cortisol was infused intravenously; arterial, portal venous, and hepatic venous blood was sampled; and liver and visceral fat were biopsied in subjects undergoing bariatric surgery.RESULTS—Ratios of arterial and portal vein D4 cortisol/cortisol_total (0.06 ± 0.01 vs. 0.06 ± 0.01) and D4 cortisol/D3 cortisol (1.80 ± 0.14 vs. 1.84 ± 0.14) did not differ, indicating that no visceral cortisol production or conversion of D4 cortisol to D3 cortisol via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) occurred. Conversely, ratios of both D4 cortisol to cortisol_total (0.05 ± 0.01; P < 0.05) and D4 cortisol to D3 cortisol (1.33 ± 0.11; P < 0.001) were lower in the hepatic vein than in the portal vein, indicating production of both cortisol and D3 cortisol by the liver. The viscera did not produce either cortisol (−8.1 ± 2.6 μg/min) or D3 cortisol (−0.2 ± 0.1 μg/min). In contrast, the liver produced both cortisol (22.7 ± 3.90 μg/min) and D3 cortisol (1.9 ± 0.4 μg/min) and accounted for all splanchnic cortisol and D3 cortisol production. Additionally, 11β-HSD-1 mRNA was approximately ninefold higher (P < 0.01) in liver than in visceral fat. Although 11β-HSD-2 gene expression was very low in visceral fat, the viscera released cortisone (P < 0.001) and D3 cortisone (P < 0.01) into the portal vein.CONCLUSIONS—The liver accounts for all splanchnic cortisol production in obese nondiabetic humans. In contrast, the viscera releases cortisone into the portal vein, thereby providing substrate for intrahepatic cortisol production.Although it has been long known that glucocorticoids are potent regulators of glucose, fat, and protein metabolism, glucocorticoids have not been thought to cause insulin resistance in either obese or diabetic individuals because plasma concentrations do not differ from those present in lean nondiabetic subjects. However, extra-adrenal conversion of cortisone to cortisol via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) can result in high local concentrations of cortisol. This observation focused attention on the possibility that tissue-specific synthesis of glucocorticoids may contribute to the pathogenesis of insulin resistance and other components of the so called “metabolic syndrome” (1). The enzyme 11β-HSD-2 (which converts cortisol to cortisone) is present primarily in the kidney, whereas 11β-HSD-1 (which converts cortisone to cortisol) is present in both liver and adipose tissue with in vitro activity being greater in omental than subcutaneous fat deposits (2–5). Inhibition (6) or knockout (7–9) of 11β-HSD-1 in mice improves hepatic insulin action and protects against obesity and hyperglycemia. Conversely, selective overexpression of 11β-HSD-1 in adipose tissue in mice results in development of visceral obesity, hyperglycemia, hyperlipidemia, and hypertension (7–11).Using a novel tracer infusion method, Andrew et al. (12) demonstrated that infusion of [9,11,12,12-²H₄] cortisol (D4 cortisol) in fasting, nondiabetic humans resulted in the formation of measurable amounts of plasma [9,12,12-²H₃] cortisol (D3 cortisol). Because conversion of D4 cortisol to D3 cortisone by 11β-HSD-2 results in the loss of the 11 α-deuterium and the generation of D3 cortisone that in turn forms D3 cortisol when D3 cortisone is converted back to cortisol, this observation provides strong experimental evidence that the conversion of cortisone to cortisol occurs in humans (12). More recently, we used the same method in combination with the hepatic venous and leg catheterization techniques to determine the site(s) of conversion of cortisone to cortisol. Those studies (13) led to the discovery that rates of splanchnic cortisol production in healthy nondiabetic individuals equaled or even exceeded those produced by extrasplanchnic tissues (e.g., the adrenals). However, because concomitant uptake of cortisol also occurred within the splanchnic bed, only a small net amount of cortisol was released into the systemic circulation.Because portal venous blood was not sampled in those studies, we could not determine the individual contributions of the viscera and the liver to splanchnic cortisol production. We therefore addressed this question in a chronically catheterized conscious dog model that permitted simultaneous selective sampling of blood from an artery, the portal vein, and the hepatic vein during intravenous infusion of D4 cortisol (14). Surprisingly, we showed that the liver accounted for all of the splanchnic cortisol production in the dog without discernable release by the viscera. However, the dogs were lean, and it is unknown if the pattern of splanchnic cortisol production in dogs reflects that in humans. Therefore, it remained possible that visceral fat releases cortisol into the portal vein in obese humans, thereby exposing the liver to high local glucocorticoid concentrations.The present experiments addressed this question by selectively obtaining simultaneous samples of arterial, portal venous, and hepatic venous blood during a D4 cortisol infusion in severely obese subjects undergoing bariatric surgery. In addition, mRNA for the glucocorticoid receptor (NR3C1), 11β-HSD-1, and 11β-HSD-2 was measured in liver and visceral fat obtained during surgery. We report that the liver accounts for all of the splanchnic cortisol production in obese nondiabetic humans. In contrast, there was no detectible release of cortisol into the portal vein by the viscera. On the other hand, although the mRNA for 11β-HSD-2 in visceral fat was very low, the viscera released cortisone into the portal vein, thereby providing the liver with substrate for intrahepatic cortisol production.