Ultrastructure of spermiogenesis and mature spermatozoon of Skrjabinoporus merops (Cyclophyllidea, Metadilepididae)

The ultrastructure of the mature spermatozoon and the spermiogenesis of a cestode belonging to the family Metadilepididae is described for the first time. The mature spermatozoon of Skrjabinoporus merops is characterized by twisted peripheral microtubules, the presence of a single crested body, periaxonemal sheath and electron-dense rods, and the absence of intracytoplasmic walls and inclusions (glycogen or proteinaceous granules); no peripheral microtubules where nucleus contacts the external plasma membrane. Four morphologically distinct regions of the mature spermatozoon are differentiated. The proximal part (Region I) contains a single crested body, periaxonemal sheath is absent in some (proximal) sections and is present in others situated closer to the nucleus. The central Region II is nucleated, and is followed by Region III that contains a periaxonemal sheath. The distal pole, Region IV, is characterized by disintegration of the axoneme. Spermiogenesis follows the type III pattern (Ba and Marchand 1995) although in S. merops a slight flagellar rotation is observed. The differentiation zone is characterized by the absence of striated roots and intercentriolar body; two centrioles are present, one of which gives rise to a free flagellum. The latter rotates and undergoes proximodistal fusion with the cytoplasmic protrusion of the differentiation zone. Spermiological characters of S. merops are similar to those of the families Taeniidae and Catenotaeniidae. The mature spermatozoon differs from those of the Dilepididae (where the metadilepidid species have previously been classified) by the lack of glycogen.     

Mutations in TAX1BP3 Cause Dilated Cardiomyopathy with Septo‐Optic Dysplasia

We describe a Bedouin family with a novel autosomal recessive syndrome characterized by dilated cardiomyopathy and septo‐optic dysplasia. Genetic analysis revealed a homozygous missense mutation in TAX1BP3, which encodes a small PDZ domain containing protein implicated in regulation of the Wnt/β‐catenin signaling pathway, as the causative mutation. The mutation affects a conserved residue located at the core of TAX1BP3 binding pocket and is predicted to impair the nature of a crucial hydrophobic patch, thereby interrupting the structure and stability of the protein, and its ability to interact with other proteins. TAX1BP3 is highly expressed in heart and brain and consistent with the clinical findings observed in our patients; a knockdown of TAX1BP3 causes elongation defects, enlarged pericard, and enlarged head structures in zebrafish embryos. Thus, we describe a new genetic disorder that expands the monogenic cardiomyopathy disease spectrum and suggests that TAX1BP3 is essential for heart and brain development.     

Are Diabetes,Hypertension, and Obesity Independent Risk Factors for Endometrial Polyps?

Study ObjectiveTo investigate whether diabetes, hypertension (HTN), and obesity can be considered risk factors for endometrial polyps (EPs) independently of age and menopausal status.DesignRetrospective analysis (Canadian Task Force classification III).SettingDepartment of Obstetrics and Gynecology of the University of Foggia, Italy.PatientsA total of 353 Caucasian women undergoing office hysteroscopy to assess abnormal uterine bleeding, infertility, cervical polyps, and abnormal sonographic patterns.InterventionsDemographic characteristics and data on diabetes, HTN, and menopausal status were collected and anthropometric parameters were analyzed. Vaginoscopic hysteroscopy was performed with a 5-mm continuous-flow operative office hysteroscope. When present, EPs were treated during the same procedure by means of 5-Fr scissors or electrode.Measurements and Main ResultsIn 134 (38%) of 353 cases, EPs were found. Univariable and multivariable analysis were performed to verify the presence of a statistically significant association among age, menopause, HTN, obesity, diabetes (independent variables), and the presence of EPs. Univariable logistic analysis showed a statistically significant association among age, menopause, HTN, obesity, and the presence of EPs. However, when multivariable logistic regression was performed, all the independent variables, except age, lost statistical significance (OR 1.05, 95% CI 1.02–1.07, p <.001).ConclusionAlthough it appears that EP is a disorder of aging, the significance of diabetes, HTN, and obesity, as well as menopause, on the development of EPs should be reconsidered.     

Extended efficacy and safety of denosumab in breast cancer patients with bone metastases not receiving prior bisphosphonate therapy

PURPOSE: Denosumab, a fully human monoclonal antibody to RANKL, suppresses bone resorption. This study evaluated the effects of denosumab in i.v. bisphosphonate (IV BP)-na?ve patients with breast cancer-related bone metastases. EXPERIMENTAL DESIGN: Eligible women (n = 255), stratified by type of antineoplastic therapy, were randomized to 1 of 5 blinded denosumab cohorts or an open-label IV BP cohort. Denosumab was administered s.c. every 4 weeks (30, 120, or 180 mg) or every 12 weeks (60 or 180 mg) through 21 weeks. Final efficacy results for up to 25 weeks are reported, including percentage change from baseline in urine N-telopeptide corrected for creatinine (uNTx/Cr) and incidence of skeletal-related events (SRE). Safety results are reported through the end of follow-up (up to 57 weeks). RESULTS: At week 13 and 25, the median percent changes in uNTx/creatinine (Cr) among patients with measurable uNTx were -73% and -75% for the pooled denosumab groups and -79% and -71% for the IV BP group. Among patients with > or =1 postbaseline measurement of uNTx at week 25, 52% (109 of 208) of denosumab-treated patients and 46% (19 of 41) of IV BP-treated patients achieved >65% uNTx/Cr reduction. On-study SREs occurred in 12% (26 of 211) of denosumab-treated patients and 16% (7 of 43) of IV BP-treated patients. Overall rates of adverse events were 95% in denosumab and IV BP groups. No denosumab-related serious or fatal adverse events occurred. CONCLUSIONS: In IV BP-na?ve breast cancer patients with bone metastases, denosumab suppresses bone turnover and seems to reduce SRE risk similarly to IV BPs, with a safety profile consistent with an advanced cancer population receiving systemic therapy.     

Association of the G289S single nucleotide polymorphism in the HSD17B3 gene with prostate cancer in Italian men

BACKGROUND: Prostate cancer is a significant public health problem in this country. Substantial data support a plausible role for androgens in the etiology of this disease. The human HSD17B3 gene encodes the testicular (or type III) 17 beta-hydroxysteroid dehydrogenase enzyme, which catalyzes testosterone biosynthesis in men. METHODS: We have investigated the G289S (glycine at codon 289 replaced by serine) polymorphism at the HSD17B3 locus as a candidate single nucleotide polymorphism (SNP) for prostate cancer risk in constitutional DNA from 103 Italian prostate cancer patients and 109 Italian disease-free centenarians to assess the role of this SNP in susceptibility to prostate cancer. RESULTS: The G289S polymorphism confers a significant increase in risk for prostate cancer (odds ratio = 2.5; 95% confidence interval, 1.03-6.07) in our study population. CONCLUSION: Our data are consistent with a plausible role of the G289S SNP in prostate cancer susceptibility. Therefore, the HSD17B3 gene may be a plausible candidate gene for prostate cancer risk.     

Long-term antidepressant treatment

Major depressive disorder (MDD) is a common and costly illness. Recent research suggests that MDD is a lifelong condition for many patients. This has stimulated researchers to identify risk factors associated with an increased frequency of relapse and recurrence of major depression. One of the most important of these risk factors is an incomplete response to acute treatment. These data have led investigators to pursue techniques that enhance the acute response of patients to therapy, and study whether long-term treatment with antidepressants may prevent relapse and recurrence of MDD. Data from these trials suggest that continuation and maintenance treatment of MDD confers some protection against deteriorating back into an episode after acute treatment and against developing another episode of MDD.     

Learning outcomes in health care ethics; a case study concerning one course

Medicine, Health Care and Philosophy -     

Four new flavonol glycosides from the leaves of Astragalus caprinus

Four new flavonol 3-O-glycosides were isolated from the leaves of Astragalus caprinus. Their structures were elucidated by spectroscopic methods as rhamnocitrin-3-O-[3-hydroxy-3-methylglutaroyl(1-->6)][beta-D-apiofuranosyl(1-->2)]-beta-D-galactopyranoside (1), rhamnetin-3-O-[3-hydroxy-3-methylglutaroyl(1-->6)][beta-D-apiofuranosyl(1-->2)]-beta-D-galactopyranoside (2), kaempferol-3-O-[beta-D-xylopyranosyl(1-->3)-alpha-L-rhamnopyranosyl(1-->6)]-beta-D-galactopyranoside (3), and quercetin-3-O-[beta-D-xylopyranosyl(1-->3)-alpha-L-rhamnopyranosyl(1-->6)][beta-D-apiofuranosyl(1-->2)]-beta-D-galactopyranoside (4).     

Ultrastructural analysis of bone tissue irradiated by Er:YAG Laser

BACKGROUND AND OBJECTIVES: The use of erbium:yttrium aluminum garnet (Er:YAG) laser has been suggested for bone ablation, however, little is known about the nature of the tissue after irradiation. This study was aimed to analyze the ultrastructure of bone tissue treated with Er:YAG laser, as compared to those treated with CO(2) laser and bur drilling. STUDY DESIGN/MATERIALS AND METHODS: Parietal bones of Wistar rats were treated and analyzed by light microscopy, transmission electron microscopy (TEM), electron diffraction analysis and energy dispersive X-ray spectroscopy (SEM-EDX). RESULTS: This study demonstrated that Er:YAG laser irradiation resulted in a very thin changed layer of approximately 30 microm thickness, which consisted of two distinct sub-layers: a superficial, greatly altered layer and a deep, less affected layer. CONCLUSIONS: The major changes found on bone surface after Er:YAG laser irradiation consisted of micro-cracking, disorganization, and slight recrystallization of the original apatites and reduction of surrounding organic matrix.