Hydroxyapatite nanorods loaded with parathyroid hormone (PTH) synergistically enhance the net formative effect of PTH anabolic therapy

Parathyroid hormone (PTH) has been a major contributor to the anabolic therapy for osteoporosis, but its delivery to bone without losing activity and avoiding adverse local effects remain a challenge. Being the natural component of bone, use of hydroxyapatite for this purpose brings a major breakthrough in synergistic anabolism. This study focuses on synthesis, characterization and evaluation of in vitro and in vivo efficacy of PTH (1-34) adsorbed hydroxyapatite nanocarrier for synergistic enhancement in the anabolic activity of PTH for bone regeneration. The negative zeta potential of this nanocarrier facilitated its affinity to the Ca²⁺ rich bone tissue and solubilization at low pH enhanced specific delivery of PTH to the resorption pits in osteoporotic bone. In this process, PTH retained its anabolic effect and at the same time an increase in bone mineral content indicated enhancement of the net formative effect of the PTH anabolic therapy.     

Cor Pulmonale Parvus in Chronic Obstructive Pulmonary Disease and Emphysema : The MESA COPD Study

Background

The classic cardiovascular complication of chronic obstructive pulmonary disease (COPD) is cor pulmonale or right ventricular (RV) enlargement. Most studies of cor pulmonale were conducted decades ago.

Objectives

This study sought to examine RV changes in contemporary COPD and emphysema using cardiac magnetic resonance (CMR) imaging.

Methods

We performed a case-control study nested predominantly in 2 general population studies of 310 participants with COPD and control subjects 50 to 79 years of age with ≥10 pack-years of smoking who were free of clinical cardiovascular disease. RV volumes and mass were assessed using magnetic resonance imaging. COPD and COPD severity were defined according to standard spirometric criteria. The percentage of emphysema was defined as the percentage of lung regions <−950 Hounsfield units on full-lung computed tomography; emphysema subtypes were scored by radiologists. Results were adjusted for age, race/ethnicity, sex, height, weight, smoking status, pack-years, systemic hypertension, and sleep apnea.

Results

Right ventricular end-diastolic volume (RVEDV) was reduced in COPD compared with control subjects (−7.8 ml; 95% confidence interval: −15.0 to −0.5 ml; p = 0.04). Increasing severity of COPD was associated with lower RVEDV (p = 0.004) and lower RV stroke volume (p < 0.001). RV mass and ejection fraction were similar between the groups. A greater percentage of emphysema also was associated with lower RVEDV (p = 0.005) and stroke volume (p < 0.001), as was the presence of centrilobular and paraseptal emphysema.

Conclusions

RV volumes are lower without significant alterations in RV mass and ejection fraction in contemporary COPD, and this reduction is related to the greater percentage of emphysema on computed tomography.     

A Qualitative Exploration to Understand the Sexual Behavior and Needs of Young Adults: A Study Among College Students of Pune,India

Indian Journal of Pediatrics - Youth and adolescents are the priority population to target the interventions as risky behaviors persist and they contribute to almost half of the new Human...     

In vitro evaluation of mechanical characteristics of a novel Patent Ductus Arteriosus (PDA) occlusion device with a new lateral pressure measurement study

Persistence of the ductus arteriosus (DA), connecting the aorta to the pulmonary artery, after birth leads to a congenital heart disease known as Patent Ductus Arteriosus (PDA). The objective of this study was to propose a new intraductal design for PDA occlusion and determine the efficacy of the new device by means of an in vitro mechanical evaluation. A novel intraductal design device called the Novel design 36 (ND36) was proposed, fabricated and tested. Mechanical tests included tests to determine the mechanical characteristics, force–displacement characteristics, stiffness, device slenderization, minimum diameter attained, insertion force required to pull device at site and lateral pressure exerted on the PDA walls. Comparative analysis was carried out with the Amplatzer Duct Occluder (AGA Medical Corporation, Golden Valley, MN). The results showed that the ND36 when fully stretched was shorter than the ADO implying an easier in vivo movement. The minimum diameter attained by ND36 is 2.52 mm which is compatible with standard catheter bores of 6–8 Fr (2–2.7 mm) bore sizes. A new setup was devised in order to carry out comparative lateral pressure measurements between the ND36 and ADO. The results showed that the ND36 exerted a pressure of 10 KPa (=75 mm Hg) and the ADO exerted 80 KPa (=600 mm Hg) over the walls of the tubes which is a physiologically promising result for the ND36 as it shows that the ND36 would exert lesser stress on the walls of the duct. The results suggest that the novel intraductal design (ND36) would prove to be a safer, reliable and effective device for PDA occlusion.     

Abortive Mitoses and Nuclear DNA Fragmentation in CD30+ Large Cells of Hodgkin's Disease

This study was undertaken to better comprehend the reasons for the scarcity of Hodgkin and Reed-Sternberg (H-RS) cells in Hodgkin's disease (HD) despite their expression of “proliferation-associated antigens”. To this end, we assessed the relative frequency of mitotic phases and nuclear damage (detected by in situ end-labeling of DNA strand breaks) in CD30⁺ large cells of nodular sclerosis and mixed cellularity HD. Our results show that a) most CD30⁺ cells in HD exhibit abortive mitoses, with a highly significant arrest at the metaphase-ana/telophase transition, and b) many of these elements, i.e. mainly H-RS cells, show fragmentation of nuclear DNA, suggesting imminent or actual death. Percentages of CD30⁺ cells that entered mitosis and those with DNA strand breaks were of a similar order of magnitude and correlated significantly in a linear fashion. These findings are consistent with the concept that cell deletion is the major cause of the paucity of H-RS cells in HD.     

Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years

Context  The incidence of nonmelanoma skin cancer is increasing rapidly among elderly persons, but little is known about its incidence in the population younger than 40 years. Objectives  To estimate the sex- and age-specific incidences of basal cell carcinoma and squamous cell carcinoma in persons younger than 40 years in Olmsted County, Minnesota, and to evaluate change in incidence over time; to describe the clinical presentation, rate of recurrence and metastasis, and histologic characteristics of these tumors in this population-based sample. Design  Population-based retrospective incidence case review. Setting  Residents of Olmsted County, Minnesota, a population with comprehensive medical records captured through the Rochester Epidemiology Project. Participants  Patients younger than 40 years with basal cell carcinoma or squamous cell carcinoma diagnosed between 1976 and 2003. Main Outcome Measures  Incident basal cell carcinomas and squamous cell carcinomas and change in incidence of these tumors over time. Results  During the study period, 451 incident basal cell carcinomas were diagnosed in 417 patients and 70 incident squamous cell carcinomas were diagnosed in 68 patients. Of these tumors, 328 were histologically confirmed basal cell carcinomas and 51 were histologically confirmed squamous cell carcinomas. Overall, the age-adjusted incidence of basal cell carcinoma per 100 000 persons was 25.9 (95% confidence interval [CI], 22.6-29.2) for women and 20.9 (95% CI, 17.8-23.9) for men. The incidence of basal cell carcinoma increased significantly during the study period among women (P<.001) but not men (P = .19). Nodular basal cell carcinoma was the most common histologic subtype; 43.0% of tumors were solely nodular basal cell carcinoma and 11.0% had a mixed composition, including the nodular subtype. The incidence of squamous cell carcinoma was similar in men and women, with an average age- and sex-adjusted incidence per 100 000 persons of 3.9 (95% CI, 3.0-4.8); the incidence of squamous cell carcinoma increased significantly over the study period among both women (P = .01) and men (P = .04). Conclusions  This population-based study demonstrated an increase in the incidence of nonmelanoma skin cancer among young women and men residing in Olmsted County, Minnesota. There was a disproportionate increase in basal cell carcinoma in young women. This increase may lead to an exponential increase in the overall occurrence of nonmelanoma skin cancers over time as this population ages, which emphasizes the need to focus on skin cancer prevention in young adults.      

Retinoblastoma-related p107 and pRb2/p130 proteins in malignant lymphomas: distinct mechanisms of cell growth control.

pRb/p105, p107, and pRb2/p130 compose the retinoblastoma (RB) family of proteins and regulate cellular growth and differentiation. Because recent functional studies have indicated that the expression of the RB-related proteins p107 and pRb2/p130 are tightly cell cycle regulated, we were interested in investigating their expression along with cellular kinetic characteristics and proliferative features of non-Hodgkin's lymphomas (NHLs). p107 and pRb2/ p130 expression was determined immunohistochemically in biopsy specimens from 83 untreated patients with NHLs of various histiotypes. The expression of these two RB-related proteins was correlated with the mitotic index, apoptotic index, and percentages of Ki-67(+), cyclin A(+), p34(+), and cyclin B(+) cells. The overall survival rate was evaluated according to the Kaplan-Meier method and the log-rank test. We found a positive correlation between the percentages of cells positive for p107 and proliferative features such as mitotic index and percentage of Ki-67(+) and cyclin A(+) cells, whereas such correlation could not be demonstrated for the percentages of pRb2/p130 positive cells. Low immunohistochemical levels of pRb2/p130 detected in untreated patients with NHLs of various histiotypes inversely correlated with a large fraction of cells expressing high levels of p107 and proliferation-associated proteins. Such a pattern of protein expression is normally observed in continuously cycling cells. Interestingly, such cases showed the highest survival percentage (82.5%) after the observation period of 10 years. Thus, down-regulation of the RB-related pRb2/p130 protein could be one of the reasons why these cases display such a high rate of proliferation and why they respond so well to therapy.     

Discordance of pediatric morphea treatment by pediatric dermatologists

Background/Objectives

Studies describing treatment efficacy in pediatric morphea are lacking. Subspecialists have reached no consensus on how to optimally treat pediatric morphea. The objective of the current study was to describe the most common treatment practices of pediatric dermatologists worldwide who care for children with morphea.

Methods

A survey regarding topical treatment practices of pediatric morphea, with representative case‐based scenarios, was distributed to pediatric dermatologists and results were tallied.

Results

The survey response rate was 13.4%, with 110 respondents in the final analysis. The majority of respondents agreed on red violaceous rim (99%), increased local warmth (75%), raised borders (69%), and dermal thickening (64%) as signs of disease activity. Respondents had less agreement on sclerotic lesions (41%), scaling (43%), dyspigmentation (19%), and atrophy (13%) as signs of disease activity. Ninety‐two percent of respondents used primary therapy or monotherapy with topical medications, including 45% in linear morphea of the limbs and 37% in linear morphea of the head or neck. High‐potency topical corticosteroids were most commonly used (80%), although respondents did not agree on specific regimens. Sixteen different treatment regimens were selected as first‐line therapy for one case scenario of active disease.

Conclusion

The survey found large variation in how pediatric dermatologists treat pediatric morphea. Consensus treatment guidelines developed by pediatric dermatologists and pediatric rheumatologists are urgently needed regarding the efficacy of therapies for pediatric morphea. Prospective studies of treatment efficacy in pediatric morphea are urgently needed as well.