Background: Low ankle–brachial Index (ABI) identifies patients with symptomatic and asymptomatic peripheral arterial disease. The aim of this study was to correlate ABI value (normal or low) with ...1‐year clinical outcome in patients hospitalized for acute coronary syndromes or cerebrovascular diseases (CVD). Methods: ABI was measured in consecutive patients hospitalized because of acute myocardial infarction, unstable angina, stroke or transient ischemic attack (TIA). An ABI lower than or equal to 0.90 was considered abnormal. The primary outcome of the study was the composite of non‐fatal acute myocardial infarction, non‐fatal ischemic stroke, and death from any cause during the year following the index event. Results: An abnormal ABI was found in 27.2% of 1003 patients with acute coronary syndromes, and in 33.5% of 755 patients with acute CVD. After a median follow‐up of 372 days, the frequency of the primary outcome was 10.8% (57/526) in patients with abnormal ABI and 5.9% (73/1232) in patients with normal ABI odds ratio (OR) 1.96; 95% CI 1.36–2.81. Death was more common in patients with abnormal ABI (OR 2.05; 95% CI 1.31–3.22). Cardiovascular mortality accounted for 81.7% of overall mortality. ABI was predictive of adverse outcome after adjustment for vascular risk factors in the logistic regression analysis (OR 1.93; 95% CI 1.24–3.01). The predictive value of ABI was mainly accounted for by patients hospitalized for acute coronary syndromes (adverse outcome: 12.8% in patients with abnormal ABI and 5.9% in patients with normal ABI, OR 2.35; 95% CI 1.47–3.76). Conclusions: An abnormal ABI can be found in one‐third of patients hospitalized for acute coronary or cerebrovascular events and is a predictor of an adverse 1‐year outcome.
Ostreopsis cfr. ovata toxicity was estimated through acute bioassays using four crustacean species (Artemia franciscana, Tigriopus fulvus, Corophium insidiosum and Sphaeroma serratum). The epiphytic ...dinoflagellate showed significant toxicity towards all tested crustaceans, which have usually exhibited the highest mortalities with increasing the dinoflagellate cell concentrations. Furthermore, our results evidenced a higher sensitivity of A. franciscana larvae to Ostreopsis, compared with the other species. The results of our bioassays highlighted the usefulness of employing a base-set of different species rather than one derived from a single species, in order to obtain more reliable information on the algal toxicity.
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.
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 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.
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.
Different gene targeting approaches have been developed to modify endogenous genomic DNA in both human and mouse cells. Briefly, the process involves the targeting of a specific mutation in situ ...leading to the gene correction and the restoration of a normal gene function. Most of these protocols with therapeutic potential are oligonucleotide based, and rely on endogenous enzymatic pathways. One gene targeting approach, "Small Fragment Homologous Replacement (SFHR)", has been found to be effective in modifying genomic DNA. This approach uses small DNA fragments (SDF) to target specific genomic loci and induce sequence and subsequent phenotypic alterations. This study shows that SFHR can stably introduce a 3-bp deletion (deltaF508, the most frequent cystic fibrosis (CF) mutation) into the Cftr (CF Transmembrane Conductance Regulator) locus in the mouse embryonic stem (ES) cell genome. After transfection of deltaF508-SDF into murine ES cells, SFHR-mediated modification was evaluated at the molecular levels on DNA and mRNA obtained from transfected ES cells. About 12% of transcript corresponding to deleted allele was detected, while 60% of the electroporated cells completely lost any measurable CFTR-dependent chloride efflux. The data indicate that the SFHR technique can be used to effectively target and modify genomic sequences in ES cells. Once the SFHR-modified ES cells differentiate into different cell lineages they can be useful for elucidating tissue-specific gene function and for the development of transplantation-based cellular and therapeutic protocols.
Background & Aims Deoxycholate (DC) has proapoptotic and tumorigenic effects in different cell types of the gastrointestinal tract. Exposure of BHK-21 (stromal) cells to DC induces Ca2+ entry at the ...plasma membrane, which affects intracellular Ca2+ signaling. We assessed whether DC-induced increases in Ca2+ can impinge on plasma membrane properties (eg, ionic conductances) involved in cell apoptosis. Methods Single- and double-barreled microelectrodes were used to measure membrane potential (Vm ) and extracellular K+ in BHK-21 fibroblasts and Caco-2 colon carcinoma cells. Apoptosis was assessed by Hoechst labeling, propidium iodide staining, and caspase-3 and caspase-7 assays. Results DC-induced cell membrane hyperpolarization was directly measured with intracellular microelectrodes in both cell lines. Diverse Ca2+ mobilizing agents, such as membrane receptor agonists, an inhibitor of the sarco/endoplasmic reticulum Ca2+ adenosine triphosphatase and a Ca2+ ionophore, also induced increases in Vm . Removal of extracellular Ca2+ reduced the agonist- and DC-induced membrane hyperpolarization by approximately 15% and 60%, respectively. These findings indicate a prominent role for Ca2+ entry at the plasma membrane in the action of this bile salt. Blockade of Ca2+ -activated K+ conductances by charybdotoxin and apamin reduced DC-induced hyperpolarization by 75% and 64% in BHK-21 and Caco-2 cells, respectively. These inhibitors also reduced the DC-induced increase in extracellular K+ by 75% and cell apoptosis by approximately 50% in both cell lines. Conclusions Ca2+ -dependent K+ conductance is an important regulator of DC-induced apoptosis in stromal and colon cancer cells.
Deoxycholate (DC) has proapoptotic and tumorigenic effects in different cell types of the gastrointestinal tract. Exposure of BHK-21 (stromal) cells to DC induces Ca
2+ entry at the plasma membrane, ...which affects intracellular Ca
2+ signaling. We assessed whether DC-induced increases in Ca
2+ can impinge on plasma membrane properties (eg, ionic conductances) involved in cell apoptosis.
Single- and double-barreled microelectrodes were used to measure membrane potential (V
m) and extracellular K
+ in BHK-21 fibroblasts and Caco-2 colon carcinoma cells. Apoptosis was assessed by Hoechst labeling, propidium iodide staining, and caspase-3 and caspase-7 assays.
DC-induced cell membrane hyperpolarization was directly measured with intracellular microelectrodes in both cell lines. Diverse Ca
2+ mobilizing agents, such as membrane receptor agonists, an inhibitor of the sarco/endoplasmic reticulum Ca
2+ adenosine triphosphatase and a Ca
2+ ionophore, also induced increases in V
m. Removal of extracellular Ca
2+ reduced the agonist- and DC-induced membrane hyperpolarization by approximately 15% and 60%, respectively. These findings indicate a prominent role for Ca
2+ entry at the plasma membrane in the action of this bile salt. Blockade of Ca
2+-activated K
+ conductances by charybdotoxin and apamin reduced DC-induced hyperpolarization by 75% and 64% in BHK-21 and Caco-2 cells, respectively. These inhibitors also reduced the DC-induced increase in extracellular K
+ by 75% and cell apoptosis by approximately 50% in both cell lines.
Ca
2+-dependent K
+ conductance is an important regulator of DC-induced apoptosis in stromal and colon cancer cells.
In Italy, Residential Facilities (RFs) have completely replaced Mental Hospitals (MHs) for the residential care of mentally ill patients. We studied all patients resident in 265 randomly sampled ...Italian RFs (20% of the total).
Structured interviews focusing on each patient were conducted by trained research assistants with the manager and staff of each RF. Patients were rated with the HoNOS and the GAF, and comprehensive information about their sociodemographic and clinical status and care history were gathered.
Of the 2962 patients living in the sampled facilities, most were males (63.2%) who had never married, more than 70% were over 40 years; 85% on a pension, most commonly because of psychiatric disability. A substantial proportion (39.8%) had never worked and very few were currently employed (2.5%); 45% of the sample was totally inactive, not even assisting with domestic activities in the facility. Two-thirds had a diagnosis of schizophrenia; co-morbid or primary substance abuse were uncommon. Twenty-one per cent had a history of severe interpersonal violence, but violent episodes in the RFs were infrequent. The managers judged almost three-quarters appropriately placed in their facilities and considered that very few had short-term prospects of discharge.
Italian RFs cater for a large patient population of severely mentally ill requiring residential care. Discharge to independent accommodation is uncommon. Future studies should attempt to clarify how to match residential programmes with patients' disabilities.
BACKGROUND: Y-autosome (Y/A) translocations have been reported in association with male infertility. Different hypotheses have been made as to correlations between Y/A translocations and ...spermatogenetic disturbances. We describe an azoospermic patient with a de-novo Y;14 translocation: 45,X,dic(Y;14)(q12;p11). METHODS AND RESULTS: Cytogenetic, fluorescent in-situ hybridization (FISH) and molecular studies have been performed. A 14/22 (D14Z1/D22Z1) centromere and a Y centromere (DYZ1) probe both showed a signal on the translocation chromosome, confirming its dicentricity. Each copy of the translocation chromosome had only one primary constriction, with inactivation of the Y centromere in most (90%) of the cells. The 14 centromere was inactive in the remaining cells (10%). FISH and molecular deletion mapping analysis allowed acute assignment of the Yq breakpoint to the junction of euchromatin and heterochromatin (Yq12), distal to the AZF gene location (Yq11). CONCLUSIONS: This study supports the hypothesis that in Y/A translocations infertility might be related to meiotic disturbances with spermatogenetic arrest. In addition, sex chromosome molecular investigations, performed on single spermatids, suggest a highly increased risk of producing chromosomally abnormal embryos.
Although residential facilities (RFs) have largely replaced mental hospitals (MHs) in most developed countries for the long-term residential care of severely impaired patients, the process of care in ...RFs has not been well studied. The aim of this paper is to investigate the process of care in 265 RFs, representing 19.3% of all RFs in Italy, and to devise a classification of RFs based on process characteristics.
Structured interviews were conducted with the manager and staff of each RF. Residents were evaluated using standardized rating instruments.
Most RFs had specific admission criteria, with one third having a waiting list that averaged about 3 months. There was no formal limitation to the length of stay in three quarters of RFs, and turnover rates were very low. Although a homelike atmosphere was found in many RFs, most facilities had restrictive rules on patients' daily lives and behaviours. RFs carried out several external activities targeted at integrating patients within the local community. Standardized assessment instruments and written treatment plans were rarely used. A cluster analysis based on the levels of restrictiveness and the standardization of the process of care classified RFs into five groups that differed with respect to daily staff coverage, size, geographical distribution and proportion of former MH residents. No significant intercluster differences were associated with the current clinical and psychosocial characteristics of residents, or with several other outcome variables.
This study provides naturalistic evidence of the heterogeneity of the process of residential care on a large scale. Future efforts should focus on developing an empirical classification of RFs, as well as on national and international standards of care and staffing to address patients' needs.
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