Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.     

Kaposi sarcoma following postmastectomy lymphedema

Classical Kaposi sarcoma (KS) usually appears on lower extremities accompanied or preceded by local lymphedema. However, the development in areas of chronic lymphedema of the arms following mastectomy, mimicking a Stewart–Treves syndrome, has rarely been described. We report an 81‐year‐old woman who developed multiple, erythematous to purple tumors, located on areas of post mastectomy lymphedema. Histopathological examination evidenced several dermal nodules formed by spindle‐shaped cells that delimitated slit‐like vascular spaces with some red cell extravasation. Immunohistochemically, the human herpesvirus type 8 (HHV‐8) latent nuclear antigen‐1 was detected in the nuclei of most tumoral cells confirming the diagnosis of KS. Lymphedema could promote the development of certain tumors by altering immunocompetence. Although angiosarcoma (AS) is the most frequent neoplasia arising in the setting of chronic lymphedema, other tumors such as benign lymphangiomatous papules (BLAP) or KS can also develop in lymphedematous limbs. It is important to establish the difference between AS and KS because their prognosis and treatment are very different. Identification by immunohistochemistry of HHV‐8 is useful for the distinction between KS and AS or BLAP.     

Riesgo de recurrencia tras retirada de la anticoagulación en pacientes con enfermedad tromboembólica venosa no provocada: validación externa del nomograma de Viena y del modelo predictivo DASH

IntroductionScales for predicting venous thromboembolism (VTE) recurrence are useful for deciding the duration of the anticoagulant treatment. Although there are several scales, the most appropriate for our setting has not been identified. For this reason, we aimed to validate the DASH prediction score and the Vienna nomogram at 12 months.MethodsThis was a retrospective study of unselected consecutive VTE patients seen between 2006 and 2014. We compared the ability of the DASH score and the Vienna nomogram to predict recurrences of VTE. The validation was performed by stratifying patients as low-risk or high-risk, according to each scale (discrimination) and comparing the observed recurrence with the expected rate (calibration).ResultsOf 353 patients evaluated, 195 were analyzed, with an average age of 53.5 ± 19 years. There were 21 recurrences in 1 year (10.8%, 95% CI: 6.8%-16%). According to the DASH score, 42% were classified as low risk, and the rate of VTE recurrence in this group was 4.9% (95% CI: 1.3%-12%) vs. the high-risk group that was 15% (95% CI: 9%-23%) (p <.05). According to the Vienna nomogram, 30% were classified as low risk, and the rate of VTE recurrence in the low risk group vs. the high risk group was 4.2% (95% CI:0.5%-14%) vs. 16.2% (95% CI: 9.9%-24.4%) (p <.05).ConclusionsOur study validates the DASH score and the Vienna nomogram in our population. The DASH prediction score may be the most advisable, both because of its simplicity and its ability to identify more low-risk patients than the Vienna nomogram (42% vs. 30%).     

Sociodemographic characteristics of the neighborhood and depressive symptoms in older adults: using multilevel modeling in geriatric psychiatry.

OBJECTIVE: Neighborhood sociodemographic characteristics may be important to the mental health of older adults who have decreased mobility and fewer resources. Our objective was to examine the association between neighborhood context and level of depressive symptomatology in older adults in a diverse geographic region of central North Carolina. METHODS: The sample included 2,998 adults 65 or older residing in 91 census tracts. Depressive symptoms were measured using the Center for Epidemiologic Studies-Depression scale (CES-D). Neighborhoods were characterized by five census-based characteristics: socioeconomic disadvantage, socioeconomic advantage, racial/ethnic heterogeneity, residential stability, and age structure. RESULTS: In ecologic level analyses, level of census tract socioeconomic disadvantage was associated with increased depressive symptoms. To determine whether neighborhood context was associated with depressive symptoms independently of individual characteristics, the authors used multilevel modeling. The authors examined the ability of each of five neighborhood (level 2) characteristics to predict a level 1 outcome (CES-D symptoms) controlling for the effects of individual (level 1) characteristics. Younger age, being widowed, lower income, and having some functional limitations were associated with increased depression symptoms conditional on census tract random effects. However, none of the neighborhood characteristics was significantly associated with depression symptoms, conditional on census tract random effects, either unadjusted or adjusted for individual characteristics. CONCLUSION: Any observed association between neighborhood sociodemographic characteristics and individual depressive symptoms in our sample may reflect the characteristics of the individuals who reside in the neighborhood rather than the neighborhood characteristics themselves. The use of multilevel modeling is important to separate these effects.     

Combined anti-bradycardia/anti-tachycardia pacemaker-cardioverter-defibrillator systems in patients with recurrent ventricular tachyarrhythmias]

In 41 patients with recurrent sustained ventricular tachycardia and/or ventricular fibrillation an integrated pacemaker-defibrillator-system (PCD, Medtronic, model 7216 A or 7217 B) was implanted. In 21 out of 24 (88%) patients a new transvenous implantation technique in combination with a subcutaneous patch electrode was used. The implanted devices comprise antibradycardiac pacemaker functions, two different forms of antitachycardiac pacemaker functions (ramp and burst pacing), and internal cardioversion or defibrillation capabilities. During a mean follow-up of 8 months 147 episodes of ventricular tachycardia were detected, 131 of them were terminated successfully by antitachycardiac pacing; in 13 episodes internal cardioversion was applied to revert ventricular tachycardia. Twenty-seven episodes of ventricular fibrillation or rapid ventricular tachycardia (greater than 200/min) were detected and successfully terminated by internal defibrillation. In six patients with intermittent rapid atrial fibrillation, change of antiarrhythmic therapy was required to avoid activation of the device. The new integrated pacemaker-defibrillator systems improve therapy in patients with life-threatening tachyarrhythmias by reducing the number of internal cardioversions/defibrillations; the non-thoracotomy approach reduces the post operative risk.     

Integrating Decision Making and Mental Health Interventions Research: Research Directions

The importance of incorporating patient and provider decision-making processes is in the forefront of the National Institute of Mental Health (NIMH) agenda for improving mental health interventions and services. Key concepts in patient decision making are highlighted within a simplified model of patient decision making that links patient-level/"micro" variables to services-level/"macro" variables via the decision-making process that is a target for interventions. The prospective agenda for incorporating decision-making concepts in mental health research includes (a) improved measures for characterizing decision-making processes that are matched to study populations, complexity, and types of decision making; (b) testing decision aids in effectiveness research for diverse populations and clinical settings; and (c) improving the understanding and incorporation of preference concepts in enhanced intervention designs.     

Internal Hernias: Clinical Findings,Management, and Outcomes in 49 Nonbariatric Cases

Internal hernia, the protrusion of a viscus through a peritoneal or mesenteric aperture, is a rare cause of small bowel obstruction. We report the clinical presentation, surgical management, and outcomes of one of the largest series of nonbariatric internal hernias. Ten-year retrospective review of patients at our institution yielded 49 cases of internal hernias. Majority of patients presented with symptoms of acute (75%) or intermittent (22%) small bowel obstruction. While 16% of CT scans were suspicious for internal hernia, in no cases the preoperative diagnosis of internal hernia was made. The most frequent internal hernias were transmesenteric (57.0%) and 34 hernias (69%) were caused by previous surgery. All internal hernias were reduced and the defects were repaired. Compromised bowel was present in 22 cases and 11 patients underwent small bowel resection. The mean postoperative hospitalization was 10.9 days. The overall mortality rate from our series is 2%, and the morbidity rate is 12%. Transmesenteric hernias, as complications of previous surgeries, are the most prevalent internal hernias. Preoperative diagnosis of internal hernia is extremely difficult because of the nonspecific clinical presentation. However, if discovered promptly, internal hernias can be repaired with acceptable morbidity and mortality. Poster presentation at Digestive Disease Week, May 22, 2006, Los Angeles, California, USA.     

Implementing a simpler approach to mission-based planning in a medical school.

Changes in the education, research, and health care environments have had a major impact on the way in which medical schools fulfill their missions, and mission-based management approaches have been suggested to link the financial information of mission costs and revenues with measures of mission activity and productivity. The authors describe a simpler system, termed Mission-Aligned Planning (MAP), and its development and implementation, during fiscal years 2002 and 2003, at the School of Medicine at the University of Texas Health Science Center at San Antonio, Texas. The MAP system merges financial measures and activity measures to allow a broad understanding of the mission activities, to facilitate strategic planning at the school and departmental levels. During the two fiscal years mentioned above, faculty of the school of medicine reported their annual hours spent in the four missions of teaching, research, clinical care, and administration and service in a survey designed by the faculty. A financial profit or loss in each mission was determined for each department by allocation of all departmental expenses and revenues to each mission. Faculty expenses (and related expenses) were allocated to the missions based on the percentage of faculty effort in each mission. This information was correlated with objective measures of mission activities. The assessment of activity allowed a better understanding of the real costs of mission activities by linking salary costs, assumed to be related to faculty time, to the missions. This was a basis for strategic planning and for allocation of institutional resources.