The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass

Although the canonical transforming growth factor β signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin–dependent process, whereas increased BMP–Smad1/5 activity protected muscles from denervation-induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders

Carbon nanotubes allow capture of krypton, barium and lead for multichannel biological X-ray fluorescence imaging

The desire to study biology in situ has been aided by many imaging techniques. Among these, X-ray fluorescence (XRF) mapping permits observation of elemental distributions in a multichannel manner. However, XRF imaging is underused, in part, because of the difficulty in interpreting maps without an underlying cellular ‘blueprint’; this could be supplied using contrast agents. Carbon nanotubes (CNTs) can be filled with a wide range of inorganic materials, and thus can be used as ‘contrast agents’ if biologically absent elements are encapsulated. Here we show that sealed single-walled CNTs filled with lead, barium and even krypton can be produced, and externally decorated with peptides to provide affinity for sub-cellular targets. The agents are able to highlight specific organelles in multiplexed XRF mapping, and are, in principle, a general and versatile tool for this, and other modes of biological imaging

Internal sphincterotomy reduces postoperative pain after Milligan Morgan haemorrhoidectomy

<p>Abstract</p> <p>Background</p> <p>Over the last few years, there has been increasing attention on surgical procedures to treat haemorrhoids. The Milligan-Morgan haemorrhoidectomy is still one of the most popular surgical treatments of haemorrhoids. The aim of the present work is to assess postoperative pain, together with other early and late complications, after Milligan-Morgan haemorrhoidectomy as we could observe in our experience before and after performing an internal sphincterotomy.</p> <p>Methods</p> <p>from January 1980 to May 2007, we operated 850 patients, but only 699 patients (median age 53) were included in the present study because they satisfied our inclusion criteria. The patients were divided into two groups: all the patients operated on before 1995 (group A); all the patients operated on after 1995 (group B). Since 1995 an internal sphincterotomy of about 1 cm has been performed at the end of the procedure. The data concerning the complications of these two groups were compared. All the patients received a check-up at one and six months after operation and a telephone questionnaire three years after operation to evalue medium and long term results.</p> <p>Results</p> <p>after one month 507 patients (72.5%) did not have any postoperative complication. Only 192 patients (27.46%) out of 699 presented postoperative complication and the most frequent one (23.03%) was pain. The number of patients who suffered from postoperative pain decreased significantly when performing internal sphincterotomy, going from 28.8% down to 10.45% (χ²: 10,880; p = 0,0001); 95% Confidence Interval (CI) 24.7 to 28.9 (group A) and 10.17 to 10.72 (group B). In 51 cases (7.29%) urinary retention was registered. Six cases of bleeding (0.85%) were registered. Medium and long term follow up did not show any difference among the two groups.</p> <p>Conclusion</p> <p>internal sphincterotomy: reduces significantly pain only in the first postoperative period, but not in the medium-long term follow up; does not increase the incidence of continence impairment when performed; does not influence the incidence of the other postoperative complications especially as regard medium and long term results.</p

Postoperative complications after procedure for prolapsed hemorrhoids (PPH) and stapled transanal rectal resection (STARR) procedures

Procedure for prolapsing hemorrhoids (PPH) and stapled transanal rectal resection for obstructed defecation (STARR) carry low postoperative pain, but may be followed by unusual and severe postoperative complications. This review deals with the pathogenesis, prevention and treatment of adverse events that may occasionally be life threatening. PPH and STARR carry the expected morbidity following anorectal surgery, such as bleeding, strictures and fecal incontinence. Complications that are particular to these stapled procedures are rectovaginal fistula, chronic proctalgia, total rectal obliteration, rectal wall hematoma and perforation with pelvic sepsis often requiring a diverting stoma. A higher complication rate and worse results are expected after PPH for fourth-degree piles. Enterocele and anismus are contraindications to PPH and STARR and both operations should be used with caution in patients with weak sphincters. In conclusion, complications after PPH and STARR are not infrequent and may be difficult to manage. However, if performed in selected cases by skilled specialists aware of the risks and associated diseases, some complications may be prevented

Different Molecular Signatures in Magnetic Resonance Imaging-Staged Facioscapulohumeral Muscular Dystrophy Muscles

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and is characterized by a non-conventional genetic mechanism activated by pathogenic D4Z4 repeat contractions. By muscle Magnetic Resonance Imaging (MRI) we observed that T2-short tau inversion recovery (T2-STIR) sequences identify two different conditions in which each muscle can be found before the irreversible dystrophic alteration, marked as T1-weighted sequence hyperintensity, takes place. We studied these conditions in order to obtain further information on the molecular mechanisms involved in the selective wasting of single muscles or muscle groups in this disease

A Pivotal Role of Lumbar Spinothalamic Cells in the Regulation of Ejaculation via Intraspinal Connections

Introduction.  A population of lumbar spinothalamic cells (LSt cells) has been demonstrated to play a pivotal role in ejaculatory behavior and comprise a critical component of the spinal ejaculation generator. LSt cells are hypothesized to regulate ejaculation via their projections to autonomic and motor neurons in the lumbosacral spinal cord. Aim.  The current study tested the hypothesis that ejaculatory reflexes are dependent on LSt cells via projections within the lumbosacral spinal cord. Methods.  Male rats received intraspinal injections of neurotoxin saporin conjugated to substance P analog, previously shown to selectively lesion LSt cells. Two weeks later, males were anesthetized and spinal cords were transected. Subsequently, males were subjected to ejaculatory reflex paradigms, including stimulation of the dorsal penile nerve (DPN), urethrogenital stimulation or administration of D3 agonist 7‐OH‐DPAT. Electromyographic recordings of the bulbocavernosus muscle (BCM) were analyzed for rhythmic bursting characteristic of the expulsion phase of ejaculation. In addition, a fourth commonly used paradigm for ejaculation and erections in unanesthetized, spinal‐intact male rats was utilized: the ex copula reflex paradigm. Main Outcome Measures.  LSt cell lesions were predicted to prevent rhythmic bursting of BCM following DPN, urethral, or pharmacological stimulation, and emissions in the ex copula paradigm. In contrast, LSt cell lesions were not expected to abolish erectile function as measured in the ex copula paradigm. Results.  LSt cell lesions prevented rhythmic contractions of the BCM induced by any of the ejaculatory reflex paradigms in spinalized rats. However, LSt cell lesions did not affect erectile function nor emissions determined in the ex copula reflex paradigm. Conclusions.  These data demonstrate that LSt cells are essential for ejaculatory, but not erectile reflexes, as previously reported for mating animals. Moreover, LSt cells mediate ejaculation via projections within the spinal cord, presumably to autonomic and motor neurons. Staudt MD, Truitt WA, McKenna KE, de Oliveira CVR, Lehman MN, and Coolen LM. A pivotal role of lumbar spinothalamic cells in the regulation of ejaculation via intraspinal connections. J Sex Med 2012;9:2256–2265.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93690/1/j.1743-6109.2011.02574.x.pd

Finding consistent disease subnetworks across microarray datasets

<p>Abstract</p> <p>Background</p> <p>While contemporary methods of microarray analysis are excellent tools for studying individual microarray datasets, they have a tendency to produce different results from different datasets of the same disease. We aim to solve this reproducibility problem by introducing a technique (SNet). SNet provides both quantitative and descriptive analysis of microarray datasets by identifying specific connected portions of pathways that are significant. We term such portions within pathways as “subnetworks”.</p> <p>Results</p> <p>We tested SNet on independent datasets of several diseases, including childhood ALL, DMD and lung cancer. For each of these diseases, we obtained two independent microarray datasets produced by distinct labs on distinct platforms. In each case, our technique consistently produced almost the same list of significant nontrivial subnetworks from two independent sets of microarray data. The gene-level agreement of these significant subnetworks was between 51.18% to 93.01%. In contrast, when the same pairs of microarray datasets were analysed using GSEA, t-test and SAM, this percentage fell between 2.38% to 28.90% for GSEA, 49.60% tp 73.01% for t-test, and 49.96% to 81.25% for SAM. Furthermore, the genes selected using these existing methods did not form subnetworks of substantial size. Thus it is more probable that the subnetworks selected by our technique can provide the researcher with more descriptive information on the portions of the pathway actually affected by the disease.</p> <p>Conclusions</p> <p>These results clearly demonstrate that our technique generates significant subnetworks and genes that are more consistent and reproducible across datasets compared to the other popular methods available (GSEA, t-test and SAM). The large size of subnetworks which we generate indicates that they are generally more biologically significant (less likely to be spurious). In addition, we have chosen two sample subnetworks and validated them with references from biological literature. This shows that our algorithm is capable of generating descriptive biologically conclusions.</p

Antisperm Antibody Testing: A Comprehensive Review of Its Role in the Management of Immunological Male Infertility and Results of a Global Survey of Clinical Practices

Antisperm antibodies (ASA), as a cause of male infertility, have been detected in infertile males as early as 1954. Multiple causes of ASA production have been identified, and they are due to an abnormal exposure of mature germ cells to the immune system. ASA testing (with mixed anti-globulin reaction, and immunobead binding test) was described in the WHO manual 5th edition and is most recently listed among the extended semen tests in the WHO manual 6th edition. The relationship between ASA and infertility is somewhat complex. The presence of sperm agglutination, while insufficient to diagnose immunological infertility, may indicate the presence of ASA. However, ASA can also be present in the absence of any sperm agglutination. The andrological management of ASA depends on the etiology and individual practices of clinicians. In this article, we provide a comprehensive review of the causes of ASA production, its role in immunological male infertility, clinical indications of ASA testing, and the available therapeutic options. We also provide the details of laboratory procedures for assessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are presented to guide the reader in the management of ASA and immunological male infertility. Furthermore, we report the results of a recent worldwide survey, conducted to gather information about clinical practices in the management of immunological male infertility

Post-Vasectomy Semen Analysis: Optimizing Laboratory Procedures and Test Interpretation through a Clinical Audit and Global Survey of Practices

Purpose: The success of vasectomy is determined by the outcome of a post-vasectomy semen analysis (PVSA). This article describes a step-by-step procedure to perform PVSA accurately, report data from patients who underwent post vasectomy semen analysis between 2015 and 2021 experience, along with results from an international online survey on clinical practice. Materials and methods: We present a detailed step-by-step protocol for performing and interpretating PVSA testing, along with recommendations for proficiency testing, competency assessment for performing PVSA, and clinical and laboratory scenarios. Moreover, we conducted an analysis of 1,114 PVSA performed at the Cleveland Clinic's Andrology Laboratory and an online survey to understand clinician responses to the PVSA results in various countries. Results: Results from our clinical experience showed that 92.1% of patients passed PVSA, with 7.9% being further tested. A total of 78 experts from 19 countries participated in the survey, and the majority reported to use time from vasectomy rather than the number of ejaculations as criterion to request PVSA. A high percentage of responders reported permitting unprotected intercourse only if PVSA samples show azoospermia while, in the presence of few non-motile sperm, the majority of responders suggested using alternative contraception, followed by another PVSA. In the presence of motile sperm, the majority of participants asked for further PVSA testing. Repeat vasectomy was mainly recommended if motile sperm were observed after multiple PVSA's. A large percentage reported to recommend a second PVSA due to the possibility of legal actions. Conclusions: Our results highlighted varying clinical practices around the globe, with controversy over the significance of non-motile sperm in the PVSA sample. Our data suggest that less stringent AUA guidelines would help improve test compliance. A large longitudinal multi-center study would clarify various doubts related to timing and interpretation of PVSA and would also help us to understand, and perhaps predict, recanalization and the potential for future failure of a vasectomy