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Daniel C Gonzalez,1 Kajal Khodamoradi,1 Raghav Pai,1 Kristopher Guarch,2 Zachary M Connelly,3 Emad Ibrahim,1 Himanshu Arora,1 Ranjith Ramasamy1 1Department of Urology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; 2Florida International University, Miami, FL 33199, USA; 3Louisiana State University Health Shreveport, Shreveport, LA 71103, USA; 4The Interdisciplinary Stem Cell Institute, University of Miami, Miller School of Medicine, Miami, FL 33136, USACorrespondence: Ranjith RamasamyDepartment of Urology, Miller School of Medicine, University of Miami, 1120 NW 14th St, #1551, Miami, FL 33136, USATel +1 (305)-243-7200Email Ramasamy@miami.eduBackground: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a virus that is present in most bodily fluids. However, whether SARS-CoV-2 is present in the semen remains underexplored. Thus, we systematically reviewed the existing studies on the presence of SARS-CoV-2 in semen.Methods: A literature search of the PubMed, Embase, Cochrane, Web of Science, Google Scholar, and Ovid databases was performed for articles from the dates of their inception to August 2020 using the following keywords: COVID-19, SARS-CoV2, seminal, semen, and sperm. After excluding non-human studies and articles that were not in the English language, we identified 19 relevant studies. The full text of the articles were reviewed and a total of eight articles remained after applying our selection criteria.Results: After reviewing the presence of SARS-CoV-2 in the eight different studies using semen samples, only one reported the presence of the virus. Six out of 160 total semen samples with SARS-CoV-2 positive demonstrated the presence of viral RNA, of which 2 were from males in the recovery phase and 4 from the acute phase of the infection.Conclusion: The novel nature of SARS-CoV-2 has limited the number and size of studies on semen. Nevertheless, the current literature, while limited, has confirmed the presence of SARS-CoV-2 in semen in one out of the eight reported studies and totaling 4.3% of the population screened. Taken together, the risk of the presence of SARS-CoV-2 in semen appears to be extremely low and likely negligible in recovered men. Future studies need to focus on whether complete viral particles can be seen in semen and the possibility of sexual transmission.Keywords: COVID-19, coronavirus, semen, semen parameters

Introduction: Increased hematocrit (HCT) is a common adverse effect in men on testosterone therapy (TTh). We aimed to uncover differences in HCT changes among men receiving different forms of TTh., Methods: We conducted a single-center, retrospective, matched-cohort study of patients treated for testosterone deficiency (TD) to investigate the effect of three TTh regimens on HCT. We included men who received intranasal testosterone (NT), intramuscular testosterone (TC), or subcutaneous testosterone pellet (TP) regimens between January 2011 and December 2020. We matched treatment cohorts 1:1:1 for age, body mass index (BMI), and history of obstructive sleep apnea (OSA). Those taking TTh for <16 weeks were excluded. Comparison between groups was performed with Mann-Whitney U test, Student's t-test, ANOVA, or Kruskal-Wallis test as appropriate., Results: Seventy-eight matched-cohort individuals with TD received either NT, TC, or TP. The most common TD symptoms prior to initiation of TTh were erectile dysfunction (38%), low libido (22%), and lack of energy (17%). Baseline serum testosterone and HCT were higher in NT recipients (p<0.05). As expected, all men receiving TTh were found to have increased serum testosterone levels at followup (p<0.001). Relative to their respective baselines, men receiving TC experienced the greatest increase in serum testosterone (240.8 ng/dL to 585.5 ng/dL), followed by NT (230.3 ng/dL to 493.5 ng/dL) and TP (210.8 ng/dL to 360.5 ng/dL) (all p<0.001). TC and TP were associated with significant increases in HCT (4.4% and 1.7%) while NT was associated with a decrease in HCT (-0.8%) at 16-week followup., Conclusions: When controlled for age, BMI, and OSA, men receiving NT experienced decreased HCT compared to TC or TP at 16-week followup. Intranasal testosterone, while able to increase serum testosterone levels to reference range, does not appear to have a significant impact on HCT compared to the longer-acting forms of TTh.

Purpose: Testosterone replacement therapy (TRT) can potentially cause decreased spermatogenesis and subsequent infertility. Recent studies have suggested that 17-hydroxyprogesterone (17-OHP) is a reliable surrogate for intratesticular testosterone (ITT) that is essential for spermatogenesis. We evaluated data from two ongoing open-label, randomized, two-arm clinical trials amongst different treatment preparations (Trial I) subcutaneous testosterone pellets (TP) and (Trial II) intranasal testosterone (NT) or intramuscular testosterone cypionate (TC)., Materials and Methods: Seventy-five symptomatic hypogonadal men (2 serum testosterone <300 ng/dL) were randomized into open label randomized clinical trials. Eligible subjects received 800 mg TP, 11 mg TID NT or 200 mg ×2 weeks TC. 17-OHP and Serum testosterone were evaluated at baseline and follow-up. The primary outcome was changes in 17-OHP. Secondary outcome was changes in serum testosterone. Data was analyzed by two-sample and single-sample t-tests, and determination of equal or unequal variances was computed using F-tests., Results: Median participant age was 45 years old, with overall baseline 17-OHP of 46 and serum testosterone of 223.5 ng/dL. 17-OHP significantly decreased in subjects prescribed long-acting TP or TC. The 4-month change in 17-OHP in the NT group (-33.3% from baseline) was less than the change seen in TC (-65.3% from baseline) or TP (-44% from baseline) (p=0.005). All testosterone formulations increased serum testosterone levels at follow-up, with the largest increase seen in TC (+157.6%), followed by NT (+114.3%) and TP (+79.6%) (p=0.005)., Conclusions: Short-acting nasal testosterone appear to have no impact on serum 17-OHP especially in comparison to long-acting testosterone formulations. All modalities saw significant increases in serum testosterone levels at follow-up. NT and other short acting testosterone formulations may better preserve ITT and be beneficial for hypogonadal men seeking to maintain fertility potential while on TRT., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Background: Testosterone deficiency (TD) is a prevalent condition, especially in men ≥45 years old, and testosterone therapy (TTh) can improve the quality of life in these patients., Aim: To evaluate the safety profile of compounded subcutaneous testosterone pellets and to compare the efficacy between compounded and market brand testosterone pellets for TTh: E100 (Empower Pharmacy) and Testopel (Food and Drug Administration approved), respectively., Methods: This was a prospective, phase 3, randomized, noninferiority clinical trial. We enrolled 75 men diagnosed with TD and randomized them 1:1 to a market brand group and a compounded pellet group. The patients were implanted with their respective testosterone pellets: Testopel (10 pellets of 75 mg) and E100 (8 pellets of 100 mg)., Outcomes: We evaluated adverse events after implantation and followed men at 2, 4, and 6 months for morning laboratory levels (prior to 10 am): serum testosterone, estradiol, hematocrit, and prostate-specific antigen., Results: After randomization, 33 participants were enrolled in the Testopel arm and 42 in the E100 arm. Serum testosterone levels were similar between the groups at 2, 4, and 6 months, with most men (82%) dropping to <300 ng/dL by the end of the trial. Adverse events were also similar, such as elevations in prostate-specific antigen, estradiol, and hematocrit. Most dropouts were related to persistent TD symptoms and serum testosterone <300 ng/dL, with similar rates between the groups in the study., Clinical Implications: Men treated with Testopel and E100 pellets had comparable serum testosterone levels and similar adverse event rates, providing an effective choice of long-term TTh among men with TD., Strengths and Limitations: Strengths include the prospective, randomized, single-blinded study design and adequate follow-up. Limitations include the lack of external validity and the single-institution cohort., Conclusion: E100 compounded testosterone pellets are a noninferior option of TTh as compared with Testopel for men presenting with TD., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Purpose: Varicocele repair is recommended in the presence of a clinical varicocele together with at least one abnormal semen parameter, and male infertility. Unfortunately, up to 50% of men who meet criteria for repair will not see meaningful benefit in outcomes despite successful treatment. We developed an artificial intelligence (AI) model to predict which men with varicocele will benefit from treatment., Materials and Methods: We identified men with infertility, clinical varicocele, and at least one abnormal semen parameter from two large urology centers in North America (Miami and Toronto) between 2006 and 2020. We collected pre and post-operative clinical and hormonal data following treatment. Clinical upgrading was defined as an increase in sperm concentration that would allow a couple to access previously unavailable reproductive options. The tiers used for upgrading were: 1-5 million/mL (ICSI/IVF), 5-15 million/mL (IUI) and >15 million/mL (natural conception). Thus moving from ICSI/IVF to IUI, or from IUI to natural conception, would be considered an upgrade. AI models were trained and tested using R to predict which patients were likely to upgrade after surgery. The model sorted men into categories that defined how likely they were to upgrade after surgery (likely, equivocal, and unlikely)., Results: Data from 240 men were included from both centers. A total of 45.6% of men experienced an upgrade in sperm concentration following surgery, 48.1% did not change, and 6.3% downgraded. The data from Miami were used to create a random forest model for predicting upgrade in sperm concentration. On external validation using Toronto data, the model accurately predicted upgrade in 87% of men deemed likely to improve, and in 49% and 36% of men who were equivocal and unlikely to improve, respectively. Overall, the personalized prediction for patients in the validation cohort was accurate (AUC 0.72)., Conclusions: A machine learning model performed well in predicting clinically meaningful post-varicocelectomy sperm parameters using pre-operative hormonal, clinical, and semen analysis data. To our knowledge, this is the first prediction model to show the utility of hormonal data, as well as the first to use machine learning models to predict clinically meaningful upgrading. This model will be published online as a clinical calculator that can be used in the preoperative counseling of patients., Competing Interests: RR is a consultant for: Acerus Pharmaceuticals, Boston Scientific, Coloplast, Endo Pharmaceuticals, Nestle Health; a grant recipient from Acerus Pharmaceuticals, Boston Scientific, Coloplast, Endo Pharmaceuticals, Empower Pharmacy, Olympus. Other authors have nothing to disclose., (Copyright © 2022 Korean Society for Sexual Medicine and Andrology.)

Adolescent idiopathic scoliosis (AIS) is characterized by the radiographic presence of a frontal plane curve, with a magnitude greater than 10° (Cobb technique). Diffusion MRI can be employed to assess the cerebral white matter. The aim of this study was to analyze, by means of MRI, the presence of any alteration in the connectivity of cerebral white matter in AIS patients. In this study, 22 patients with AIS participated. The imaging protocol consisted in T1 and diffusion-weighted acquisitions. Based on the information from one of the diffusion acquisitions, a whole brain tractography was performed with the MRtrix tool. Tractography is a method to deduce the trajectory of fiber bundles through the white matter based on the diffusion MRI data. By combining cortical segmentation with tractography, a connectivity matrix of size 84 × 84 was constructed using FA (fractional anisotropy), and the number of streamlines as connectomics metrics. The results obtained support the hypothesis that alterations in cerebral white matter connectivity in patients with adolescent idiopathic scoliosis (AIS) exist. We consider that the application of diffusion MRI, together with transcranial magnetic stimulation neurophysiologically, is useful to search the etiology of AIS.

Numerous studies have investigated the influence of health disparities among women with pelvic floor disorders with varied results. Racial/ethnic disparities, in particular, inconsistently indicate differences in prevalence of disease, disease severity, and treatment outcomes. We aim to review the body of literature examining racial/ethnic disparities in pelvic floor disorders, including overactive bladder, stress urinary incontinence, pelvic organ prolapse, and interstitial cystitis. A better understanding of these disparities may help guide clinicians, researchers, and advocates in providing improved education, outreach opportunities, and access to care in minority women with pelvic floor disorders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction Although women remain vastly underrepresented in urology, the proportion of female urology residents and practicing urologists has steadily increased over the last four decades. However, it remains critical to evaluate the representation of females in the pipeline when examining trainees and practicing urologists. As it pertains to leadership positions, the gender distribution among the board of directors (BOD) and committee chairs in the American Urological Association (AUA) subspecialties has not been studied to date. Therefore, we plan to analyze the proportion of females among the BOD and committee chairs in different subspecialty societies recognized by the AUA over time. Methods We conducted a cross-sectional observational study, quantitatively comparing the composition of gender in BOD and Committee Chair members belonging to different AUA-recognized subspecialty societies from 2014 to 2020. The websites for each subspecialty society were searched and contacted. Results We evaluated BODs from 10 AUA subspecialty societies and committee chair members from 6 AUA subspecialty societies. From 2014 to 2020, the total proportion of female BOD amongst all AUA sub-specialty societies did not change significantly, with a small increase from 10.6% (n = 29) to 13.5% (n = 36). However, female representation among committee chair members significantly increased from 9.8% (n = 20) to 19.2% (n = 44; p = 0.006), along with the total number of women in urology, from 897 (8.9%) to 1,375 (10.3%). Increases in female representation were seen in the Society for the Study of Male Reproduction (SSMR) from 0% to 9% and in the Indian American Urological Association (IAUA) from 4% to 13%. Of note, there were no elected female board members in the Society of Urologic Oncology (SUO) or the Urologic Society for Transplantation and Renal Surgery (USTRS) from 2014 to 2020. Conclusion Females remain a minority in leadership positions at AUA sub-specialty societies despite increased female representation in recent years. Future efforts should promote the advancement of women to positions of leadership to reflect the changing landscape of the urology workforce and surgical specialties., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Dullea et al.)

The coronavirus 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to more than 160 million infections and 3.5 million deaths globally. Men are disproportionately affected by COVID-19, having more severe disease with higher mortality rates than women. Androgens have been implicated as the underlying cause for more severe disease, as the androgen receptor has been noted to upregulate the cell surface receptors that mediate viral cell entry and infection. Unfortunately, despite testosterone's potential role in COVID-19 prognosis, androgen deprivation therapy is neither protective nor a treatment for COVID-19. Interestingly, the male reproductive organs have been found to be vulnerable in moderate to severe illness, leading to reports of erectile dysfunction and orchitis. COVID-19 viral particles have been identified in penile and testis tissue, both in live patients who recovered from COVID-19 and post mortem in men who succumbed to the disease. Although sexual transmission remains unlikely in recovered men, moderate to severe COVID-19 infection can lead to germ cell and Leydig cell depletion, leading to decreased spermatogenesis and male hypogonadism. The objective of this review is to describe the impact of SARS-CoV-2 on male reproductive health. There are still many unanswered questions as to the specific underlying mechanisms by which COVID-19 impacts male reproductive organs and the long-term sequelae of SARS-CoV-2 on male reproductive health., (© 2021 The Authors BJU International © 2021 BJU International.)

Purpose: Male ageing is often associated with defective sperm DNA remodeling mechanisms that result in poorly packaged chromatin and a decreased ability to repair DNA strand breaks. However, the impact of advanced paternal age on DNA fragmentation remains inconclusive. The aim of the present systematic review was to investigate the impact of advancing paternal age (APA) on DNA fragmentation., Materials and Methods: We conducted a thorough search of listed publications in Scopus, PubMed, and EMBASE, in accordance with the PRISMA guidelines., Results: We identified 3,120 articles, of which nineteen were selected for qualitative analysis, resulting in a sample of 40,668 men. Of the 19 articles evaluating the impact of APA on DFI% (DNA fragmentation Index) included, 4 were on Normozoospermic and subfertile men, 3 on normozoospermic, Oligoasthenoteratozoospermic and Teratozoospermic, 6 on fertile and infertile men, 4 on just infertile men, and 2 evaluated a general population. Seventeen of the ninrnteen studies demonstrated APA's effect and impact on DFI%., Conclusions: Although there was no universal definition for APA, the present review suggests that older age is associated with increased DFI. In elderly men with normal semen parameters, further studies should be performed to assess the clinical implications of DFI, as a conventional semen analysis can often fail to detect an etiology for infertility., Competing Interests: The authors have nothing to disclose., (Copyright © 2022 Korean Society for Sexual Medicine and Andrology.)

An increasing number of studies show declining sperm counts; however, semen analyses are uncommon until the evaluation for infertility. Semen analysis is a safe, reliable and relatively inexpensive screening test, assessing male fertility and directing further work-up. In young men, the use of semen analysis may identify disease prior to attempted conception and result in improved fertility potential when combined with lifestyle changes, medical or surgical therapy. Furthermore, if sperm counts are significantly low, evaluation and management for genetic causes can be initiated. Our commentary outlines why screening for male infertility in young adult men may be beneficial. We discuss options for early intervention, including sperm cryopreservation, if defects in sperm parameters are identified., (© 2021 Wiley-VCH GmbH.)

Objective: To perform a systematic review on the effects of testicular sparing surgery (TSS) on the oncological, functional, and hormonal outcomes of adults with testicular tumors., Methods: A literature search was performed after PROSPERO registration (CRD42020200842) and reported in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methods. We conducted a systematic search of Medline (Ovid), Embase, Cochrane CENTRAL, CINAHL, Scopus, Web of Science, ClinicalTrials.gov, and the WHO/ICTRP from inception to November 20, 2020. Manuscripts and published abstracts were included if they involved testis-sparing surgery (TSS) and contained data on any outcomes related to fertility, hormonal parameters, or oncological control, or if they evaluated surgical technique., Results: Our initial search yielded 3,370 manuscripts, with 269 of these screened for full-text eligibility. After our exclusion criteria were applied, 32 studies were included in the final analysis. Oncological outcomes were obtained from 12 studies (average follow-up 57.8 months), functional data from 26 studies (average follow-up 49.6 months), fertility information from 10 studies (average follow-up 55.8 months), and data on nonpalpable tumors from 11 studies (average follow-up 32.1 months). Oncological control appears to be excellent in studies that reported these outcomes. Presence of germ cell neoplasia in situ was controlled with adjuvant radiation in nearly all cases. Functional outcomes are also promising, as development of primary and compensated hypogonadism was rare. Semen parameters are poor preoperatively among men with benign and malignant testis tumors, with occasional decline after TSS. Frozen section analysis at the time of surgery appears to be very reliable, and the majority of nonpalpable tumors appear to be benign., Conclusions: TSS is a safe and efficacious technique with regards to oncological control and postoperative hormonal function based on retrospective, noncontrolled studies. TSS avoids unnecessary removal of benign testicular tissue, and should be given serious consideration in cases of nonpalpable, small tumors under 2 cm. In cases of malignancy, TSS can safely avoid anorchia in men with bilateral tumors and in men with solitary testicles. The use of the operating microscope, while theoretically promising, does not necessarily lead to better outcomes, however data are limited., Competing Interests: CONFLICT OF INTEREST JO, UB, DCG, AAS, JTW, CDR, KJ, and JR have no conflict of interest to report. RR has no conflict of interest relevant to this project. RR is a consultant for: Acerus pharmaceuticals, Boston Scientific, Coloplast, Endo Pharmaceuticals, Metuchen, and Nestle Health. RR is a grant recipient from: Boston Scientific, Coloplast, and Endo Pharmaceuticals.

Although a wide array of interventions exist for men seeking fertility after vasectomy, up to 6% of them will elect for a vasectomy reversal. While the widespread adoption of telemedicine promises convenience and improved access, lack of ability to do a physical examination may hinder appropriate counselling. Although vasectomy reversal is successfully completed in most of the men either with a vasovasostomy or a vasoepididymostomy, there could be various reasons for the inability to successfully complete the operation. Our commentary outlines the reasons why a vasectomy reversal is not possible or successful. We also discuss a pre-operative management algorithm in men seeking vasectomy reversal to ensure appropriate counselling with a thorough pre-operative history, physical examination and on occasion, hormonal evaluation., (© 2021 Wiley-VCH GmbH.)

Klinefelter syndrome (KS) is an uncommon chromosomal disorder in males that has a variable clinical appearance. Classic KS involves an extra X chromosome, (47, XXY), although other variations may exist, including a milder mosaic form as well as multiple extra sex chromosomes with more dramatic phenotypes. KS is underdiagnosed, especially pre-pubertally, owing to a paucity of concrete clinical signs; however, diagnostic rates increase during and after puberty, as the consequences of hypergonadotropic hypogonadism begin to manifest. Testicular failure causing decreased circulating testosterone (T) and germ cell depletion, a hallmark feature in KS, commonly begins shortly after the onset of puberty and leads to the most commonly recognized KS traits: small testes, azoospermia, gynecomastia, decreased facial and pubic hair. While many KS men maintain adequate T levels leading up to young adulthood, some may have lower T levels at an earlier age leading to varied levels of androgenization and clinical KS features. At certain critical time points, absent or decreased T may alter the development of normal male reproductive organs, external genitalia, development of secondary sexual characteristics and spermatogenesis. Testicular failure in utero may lead to ambiguous genitalia, cryptorchidism and/or hypospadias, all of which depend on fetal T production. In the neonatal period and childhood, decreased T levels during the mini-puberty of infancy may negatively impact germ cell differentiation and male neuropsychological development. Finally, decreased T during pubertal and young adulthood can lead to decreased virilization during puberty, eunuchoid skeleton and decreased spermatogenesis. Depending on the timing of the testicular failure, a reproductive window of sperm production may exist to achieve paternity for KS men. The presence or absence of clinical characteristics reflecting decreased androgenization provides an insight to the relative testicular function during these developmental time points for those with KS and contributes to variability within the syndrome., Competing Interests: Conflicts of interest statement The authors have no relevant conflicts of interests to disclose., (Copyright © 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

The measurement of static vertical deflections on bridges continues to be a first-level technological challenge. These data are of great interest, especially for the case of long-term bridge monitoring; in fact, they are perhaps more valuable than any other measurable parameter. This is because material degradation processes and changes of the mechanical properties of the structure due to aging (for example creep and shrinkage in concrete bridges) have a direct impact on the exhibited static vertical deflections. This paper introduces and evaluates an approach to monitor displacements and rotations of structures using a novel laser and video-based displacement transducer (LVBDT). The proposed system combines the use of laser beams, LED lights, and a digital video camera, and was especially designed to capture static and slow-varying displacements. Contrary to other video-based approaches, the camera is located on the bridge, hence allowing to capture displacements at one location. Subsequently, the sensing approach and the procedure to estimate displacements and the rotations are described. Additionally, laboratory and in-service field testing carried out to validate the system are presented and discussed. The results demonstrate that the proposed sensing approach is robust, accurate, and reliable, and also inexpensive, which are essential for field implementation., Competing Interests: The authors declare no conflict of interest.

Deformation of the spine following vertebral compression fracture (VCF) can be associated with severe spinal dysfunction. Anatomical restoration is described as the complete reduction and stable fixation of the fracture with the goal to restore the pre-fracture local and global spine properties. The essential need to obtain endplate reduction, and consider the whole vertebral body in the management of vertebral fractures is pointed out. A new 3D imaging technique is described. A new assessment method based on CT scans 3D reconstructions was developed. This new method was used to assess the anatomical restoration of the fractured vertebrae. A procedure consisting in placing two expandable titanium implants for fracture reduction, together with stabilization with a high viscosity PMMA cement was used to demonstrate the method. The cases presented here are demonstrating that this 3D-mapping software is a tool which can address the lack of a valid, reproducible and user-friendly method to evaluate the anatomical restoration in VCF. The evaluation of the anatomical restoration of the fractured vertebrae raises some issues in terms of interpretation because of a lack of consensus in the existing reporting methods. A 3D-reconstruction method, using CT scans and a newly-developed software, is proposed to evaluate the anatomical restoration in a clear, valid, reproducible and user-friendly way.

Riboswitches are highly structured RNA molecules that control genetic expression by altering their structure as a function of metabolite binding. Accumulating evidence suggests that riboswitch structures are highly dynamic and perform conformational exchange between structural states that are important for the outcome of genetic regulation. To understand how ligand binding influences the folding of riboswitches, it is important to monitor in real time the riboswitch folding pathway as a function of experimental conditions. Single-molecule FRET (sm-FRET) is unique among biophysical techniques to study riboswitch conformational changes as it allows to both monitor steady-state populations of riboswitch conformers and associated interconversion dynamics. Since FRET fluorophores can be attached to virtually any nucleotide position, FRET assays can be adapted to monitor specific conformational changes, thus enabling to deduce complex riboswitch folding pathways. Herein, we show how to employ sm-FRET to study the folding pathway of the S-adenosylmethionine (SAM) and how this can be used to understand very specific conformational changes that are at the heart of riboswitch regulation mechanism.

Wheat gluten proteins are considered to have the unique ability to form viscoelastic matrices that are essential for breadmaking. This study shows that maize seed storage protein (zein), if properly treated, can be made to function similarly to gluten at the protein secondary structure level with concomitant improved viscoelasticity. Here, we propose the concept of a small amount of coprotein (high molecular weight glutenin or casein) acting to stabilize a build-up of β-sheet structure in a zein-based dough, thus creating a viscoelastic matrix that is retained over time. This discovery is relevant to the need for gluten replacement viscoelastic proteins for wheat intolerant individuals and as well opens possibilities of creating wheatlike cereal varieties that could more cheaply substitute for wheat imports in developing countries.

A method to measure thermo-mechanical properties of pharmaceutical and polymeric powders was developed. The measurements are conducted by characterizing the material's response to applied acoustic waves. Measurements were performed using griseofulvin, felodipine and indomethacin as model drugs and polyethylene oxide (MW=200,000, 900,000, 2,000,000Da) as model polymers. The method employed measures the mechanical impedance enabled the calculation of the powder rheological and thermo-mechanical properties. Measurements attained with this new technique are compared with measurements made using differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). The new method detects the melting and glass transitions events while providing complementary information to that provided by DSC and DMA., (Copyright 2010 Elsevier B.V. All rights reserved.)

Rapid weight gain in childhood is associated with increased risk of chronic diseases in adults. C-reactive protein (CRP) is a mediator of atherosclerosis and chronically elevated levels predict cardiovascular outcomes. The effects of life course weight gain on CRP levels are not clear. The 1982 Pelotas (Brazil) birth cohort study (n = 5,914) has prospectively collected weight and health data at several follow-ups since birth. The most recent was in 2004-05, when 77.4% of the cohort was traced and CRP levels were measured in 89% of those interviewed (n = 3827). Geometric mean (SE) C-reactive protein levels were 0.89 mg/l (0.03) and 1.66 mg/l (0.04) in men and women, respectively. In analyses adjusted for confounding variables, weight gain in infancy showed a weak negative association among males, but from the second year onwards, weight gain was positively associated with CRP levels. In females, weight gain was associated with higher CRP at every period tested. The strongest associations were observed in the most recent (18-23 years) period; CRP ratios (95% CI) per z score increase in weight gain were 1.78 (1.57-2.00) and 1.52 (1.30-1.78) for men and women, respectively. Males who were stunted at 2 years and centrally obese at 23 years had the highest CRP levels (P = 0.002 for interaction). In summary, rapid weight gain throughout life predicted higher CRP levels. Public health efforts need to tackle chronic under-nutrition in infancy, together with rapid weight gain in later childhood and adolescence, especially in countries undergoing the nutritional transition.

Calcium metabolism was studied in 47 patients with borderline or lepromatous leprosy. Total and ionized calcium, phosphorus, creatinine, total alkaline phosphatase, parathyroid hormone (PTH), 25-hydroxy vitamin D [25(OH)D], and 1,25-dihydroxy vitamin D [1,25(OH)2D] were measured in serum; calcium and total hydroxyproline were determined in urine. Total subperiosteal diameter and medullar cavity diameter were measured on an X-ray of the hand of all patients. Average values were within normal ranges for all of the biochemical determinations. Total serum calcium was moderately below the normal range in eight patients but ionized calcium levels were within the normal ranges in all of the patients. Four patients, all of them with lepromatous leprosy, had levels of 1,25(OH)2D higher than normal but none of them was hypercalcemic and PTH levels were within normal range. Although all values were within the normal ranges, lepromatous leprosy patients had lower total calcium, higher alkaline phosphatase, and higher urinary hydroxyproline than borderline leprosy patients (9.1 +/- 0.4 vs 9.4 +/- 0.3 mg%, p < 0.001; 10.3 +/- 2.9 vs 7.4 +/- 2.3 King-Armstrong units, p < 0.02 and 27.2 +/- 12 vs 19.4 +/- 5.6 mg/24 hr, p < 0.02, respectively). No differences were found between patients and controls in the average micrometric measurements of the second metacarpal bone but significant osteopenia was found in 19% of the patients. The main finding of the present study in a representative sample of leprosy patients is that the average total serum calcium was in the lowest limit of the normal range, but the ionized serum calcium was in the middle of the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitonin has an uncertain role in the preservation of bone mass. Since surgical thyroidectomy abolishes the calcitonin secretion in response to calcium, the bone mineral density at the radius shaft and lumbar spine was measured in 60 patients (5 men, 16 premenopausal, 34 postmenopausal euparathyroid and 5 postmenopausal hypoparathyroid women) who had undergone near total thyroidectomy for thyroid cancer 8.4 +/- 0.7 years before the study. All patients were maintained on suppressive doses of thyroid hormones. Bone mineral density values of the radius shaft (expressed as Z-score) of 34 postmenopausal euparathyroid women was significantly below the normal average (mean +/- SEM = -0.59 +/- 0.2; p = 0.01). Bone mineral density of the lumbar spine was also below the normal average although the difference only approached statistical significance (-0.36 +/- 0.2; 0.05 less than p less than 0.1). The bone mineral density of neither the radius nor the spine differed from normal levels in the premenopausal women and the postmenopausal hypoparathyroid women. Unexpectedly, the bone mineral density of the spine was significantly increased in the 5 thyroidectomized men. The results indicate that thyroidectomized women have a diminished bone mass after the menopause only if parathyroid function is normal. Since the patients were receiving thyroid hormone at suppressive doses, the present study is not able to separate the relative contributions of calcitonin deficit and exogenous thyroid on bone mass loss.

The adult respiratory distress syndrome is a major cause of morbidity and mortality in critical care patients. Lung injury in this syndrome is frequently associated with lung infection. The combined insults result in an influx of neutrophils and damage to the pulmonary epithelium. We investigated whether active neutrophil elastolytic activity was present in the bronchoalveolar fluid in baboons with mild or moderate hyperoxic lung injury and infection. Group A (N = 7) was exposed for 6 days to FIO2 = 0.8 and then inoculated by intratracheal bolus with Pseudomonas aeruginosa strain DGI-R130 (PA); the FIO2 was reduced to 0.5. Group B (N = 6) was exposed to similar concentrations of inspired oxygen but inoculated with buffered saline. Antibiotics included parenteral penicillin and topical gentamicin and polymyxin B. All 3 were given continuously in group B but stopped 24 h prior to PA inoculation in group A. Bronchoalveolar lavage fluid was collected 1 week before oxygen administration, when the FIO2 was reduced (day 6 or 7) and prior to necropsy (day 11). Hemodynamic, pulmonary function, microbiological, and biochemical variables were studied. Injured, infected animals (group A) had significant elevations of mean pulmonary artery pressure and decreases in total lung capacity and PaO2 compared both to baseline and to group B at day 11. At autopsy, group A had significant increases of bronchoalveolar lavage fluid (BALF) neutrophils and bacterial pathogens. Elastase levels in BALF (equal to 0 at baseline) rose to 136 +/- 98 ng/ml in group A vs. 6 +/- 14 ng/ml in group B. The elastase was inhibited by inhibitors of serine proteases including ones specific for neutrophil elastase. On Sephacryl S-300 chromatography the elastase activity eluted near human alpha 2-macroglobulin and separated from other proteolytic activity. These studies demonstrate a significant level of elastase in BALF from injured, infected baboons compared to injured, uninfected animals.