Molecular markers of telomere dysfunction and senescence are common findings in the usual interstitial pneumonia pattern of lung fibrosis.

AIMS: Idiopathic pulmonary fibrosis (IPF) is a genetically mediated, age-associated, progressive form of pulmonary fibrosis characterised pathologically by a usual interstitial pneumonia (UIP) pattern of fibrosis. The UIP pattern is also found in pulmonary fibrosis attributable to clinical diagnoses other than IPF (non-IPF UIP), whose clinical course is similarly poor, suggesting common molecular drivers. This study investigates whether IPF and non-IPF UIP lungs similarly express markers of telomere dysfunction and senescence. METHODS AND RESULTS: To test whether patients with IPF and non-IPF UIP share molecular drivers, lung tissues from 169 IPF patients and 57 non-IPF UIP patients were histopathologically and molecularly compared. Histopathological changes in both IPF and non-IPF UIP patients included temporal heterogeneity, microscopic honeycombing, fibroblast foci, and dense collagen fibrosis. Non-IPF UIP lungs were more likely to have lymphocytic infiltration, non-caseating granulomas, airway-centred inflammation, or small airways disease. Telomeres were shorter in alveolar type II (AECII) cells of both IPF and non-IPF UIP lungs than in those of age-similar, unused donor, controls. Levels of molecular markers of senescence (p16 and p21) were elevated in lysates of IPF and non-IPF UIP lungs. Immunostaining localised expression of these proteins to AECII cells. The mucin 5B (MUC5B) gene promoter variant minor allele frequency was similar between IPF and non-IPF UIP patients, and MUC5B expression was similar in IPF and non-IPF UIP lungs. CONCLUSIONS: Molecular markers of telomere dysfunction and senescence are pathologically expressed in both IPF and non-IPF UIP lungs. These findings suggest that common molecular drivers may contribute to the pathogenesis of UIP-associated pulmonary fibrosis, regardless of the clinical diagnosis.

The methylation status of TNF-α and SOCS3 promoters and the regulation of these gene expressions in patients with Behçet's disease.

Introduction: The aim of this study was to evaluate the methylation status of TNF-α and SOCS3 promoters in patients with BD and compare them with a healthy group.Method: This was a case-control study, in which 47 subjects with BD and 61 individuals as the control participated. Blood samples were collected from all the participants. Then, PBMCs were isolated using the Ficoll method and methylation of considered sites was investigated using the qMS-PCR technique after DNA extraction by the rapid genomic DNA extraction method and its analysis with Nano-drop.Results: The methylation and expression of TNF-α showed that the methylation level significantly declined in the patient in comparison with the healthy (p < 0.05). Moreover, the results on the mean expression showed that it significantly increased in the patient group, as compared with the healthy group (p < 0.05). In addition, the expression of the SOCS3 gene was not significantly different between the patients and healthy subjects while the level of SOCS3 methylation was significantly higher in the patient group than that in the healthy group (p < 0.05).Discussion: The present study revealed that the gene expression of TNF-alpha increased in BD patients, suggesting that TNF-alpha likely has a role in the pathogenesis of BD.

Obesity-Related Hypogonadism in Women.

Obesity-related hypogonadotropic hypogonadism is a well-characterized condition in men (termed male obesity-related secondary hypogonadism; MOSH); however, an equivalent condition has not been as clearly described in women. The prevalence of polycystic ovary syndrome (PCOS) is known to increase with obesity, but PCOS is more typically characterized by increased gonadotropin-releasing hormone (GnRH) (and by proxy luteinizing hormone; LH) pulsatility, rather than by the reduced gonadotropin levels observed in MOSH. Notably, LH levels and LH pulse amplitude are reduced with obesity, both in women with and without PCOS, suggesting that an obesity-related secondary hypogonadism may also exist in women akin to MOSH in men. Herein, we examine the evidence for the existence of a putative non-PCOS "female obesity-related secondary hypogonadism" (FOSH). We précis possible underlying mechanisms for the occurrence of hypogonadism in this context and consider how such mechanisms differ from MOSH in men, and from PCOS in women without obesity. In this review, we consider relevant etiological factors that are altered in obesity and that could impact on GnRH pulsatility to ascertain whether they could contribute to obesity-related secondary hypogonadism including: anti-Müllerian hormone, androgen, insulin, fatty acid, adiponectin, and leptin. More precise phenotyping of hypogonadism in women with obesity could provide further validation for non-PCOS FOSH and preface the ability to define/investigate such a condition.

Stromal CD10 expression in gastric adenocarcinoma.

Gastric adenocarcinoma is a malignant neoplasm of the gastric mucosa composed of neoplastic cells and supporting stroma as with any neoplasm. Stromal myofibroblasts have an essential role in creating the tumor-promoting environment. They express certain substances, such as CD10. In this study, stromal CD10 expression was investigated by immunohistochemistry in gastric carcinoma, and its association with specific clinicopathological parameters was analyzed. Formalin-fixed paraffin-embedded blocks of 80 gastric adenocarcinoma cases were collected retrospectively in a private laboratory of the Rizgary Teaching Hospital for 2 years (January 2018-January 2020). Finally, the immunohistochemical study of CD10 expression in stromal cells was performed. According to the results, stromal CD10 immunoreactivity was detected in 15% of the cases. Furthermore, a statistically significant correlation was observed between stromal CD10 and the tumor type (P=0.015). However, no statistically significant relationship was identified between stromal CD10 expression and patients' age, gender, lymphovascular invasion, lymph node status, and tumor stage and grade. The results suggest a statistically significant positive correlation between stromal CD10 expression and tumor type.

Resident and nurse perspectives on the use of secure text messaging systems.

BACKGROUND: As hospitals shift away from pagers and towards secure text messaging systems (STMS), limited research exists on the drawbacks of such systems. Preliminary data show that introduction of STMS can lead to a dramatic increase in interruptions, which may contribute to medical errors. OBJECTIVE: This study aimed to investigate residents' and nurses' experiences with STMS at a quaternary care children's hospital. DESIGN: This was a qualitative study with focus groups. SETTING AND PARTICIPANTS: Participants were pediatric residents and nurses at Lucile Packard Children's Hospital. INTERVENTION: Focus groups were audio recorded, transcribed verbatim, and coded by 2 independent coders. Codes were discussed until consensus was reached. MAIN OUTCOME AND MEASURES: Data was analyzed through a thematic, descriptive content analysis approach. Themes were developed alongside a framework of teamwork, patient safety, and clinician well-being. RESULTS: Three resident focus groups (n = 14) and three nurse focus groups (n = 21) were held. Six themes were identified: (1) STMS can facilitate teamwork through multiple communication modalities and technological features. (2) STMS can negatively impact teamwork by decreasing face-to-face communication and frontline decision-making. (3) STMS can promote patient safety through closed-loop communication and ready access to team members. (4) STMS can negatively impact patient safety through alarm fatigue, interruptions, and miscommunication. (5) STMS can positively impact clinician well-being through satisfaction and relationship building. (6) STMS can negatively impact clinician well-being through increased stress related to communication volume. CONCLUSION: Use of STMS in the hospital setting has many advantages as well as drawbacks. With appropriate guidelines and training designed to mitigate the drawbacks, STMS have the potential to be valuable means of communication for healthcare team members.

Inhibition of calpain delays early muscle atrophy after rotator cuff tendon release in sheep.

Chronic rotator cuff (RC) tears are characterized by retraction, fat accumulation, and atrophy of the affected muscle. These features pose an intractable problem for surgical repair and subsequent recovery, and their prevention may be easier than reversal. Using an established ovine model, we tested the hypothesis that inhibition of the protease calpain mitigates m. infraspinatus atrophy by preservation of the myofibers' structural anchors in the sarcolemma (the costameres). Already 2 weeks of distal tendon release led to a reduction in muscle volume (-11.6 ± 9.1 cm3 , P = 0.038) and a 8.3% slow-to-fast shift of the fiber area (P = 0.046), which were both entirely abolished by chronic local administration of the calpain inhibitor calpeptin alone, and in combination with sildenafil. Calpain inhibition blunted the retraction of the muscle-tendon unit by 0.8-1.0 cm (P = 0.020) compared with the control group, and prevented cleavage of the costameric protein talin. Calpain 1 and 2 protein levels increased in the medicated groups after 4 weeks, counteracting the efficacy of calpeptin. Hence atrophic changes emerged after 4 weeks despite ongoing treatment. These findings suggest that the early muscular adaptations in the specific case of RC tear in the ovine model are indistinguishable from the atrophy and slow-to-fast fiber transformation observed with conventional unloading and can be prevented for 2 weeks. Concluding, calpain is a potential target to extend the temporal window for reconstruction of the ruptured RC tendon before recovery turns impossible.

SPOP-Mutated/CHD1-Deleted Lethal Prostate Cancer and Abiraterone Sensitivity.

Purpose: CHD1 deletions and SPOP mutations frequently cooccur in prostate cancer with lower frequencies reported in castration-resistant prostate cancer (CRPC). We monitored CHD1 expression during disease progression and assessed the molecular and clinical characteristics of CHD1-deleted/SPOP-mutated metastatic CRPC (mCRPC).Experimental Design: We identified 89 patients with mCRPC who had hormone-naive and castration-resistant tumor samples available: These were analyzed for CHD1, PTEN, and ERG expression by IHC. SPOP status was determined by targeted next-generation sequencing (NGS). We studied the correlations between these biomarkers and (i) overall survival from diagnosis; (ii) overall survival from CRPC; (iii) duration of abiraterone treatment; and (iv) response to abiraterone. Relationship with outcome was analyzed using Cox regression and log-rank analyses.Results: CHD1 protein loss was detected in 11 (15%) and 13 (17%) of hormone-sensitive prostate cancer (HSPC) and CRPC biopsies, respectively. Comparison of CHD1 expression was feasible in 56 matched, same patient HSPC and CRPC biopsies. CHD1 protein status in HSPC and CRPC correlated in 55 of 56 cases (98%). We identified 22 patients with somatic SPOP mutations, with six of these mutations not reported previously in prostate cancer. SPOP mutations and/or CHD1 loss was associated with a higher response rate to abiraterone (SPOP: OR, 14.50 P = 0.001; CHD1: OR, 7.30, P = 0.08) and a longer time on abiraterone (SPOP: HR, 0.37, P = 0.002, CHD1: HR, 0.50, P = 0.06).Conclusions: SPOP-mutated mCRPCs are strongly enriched for CHD1 loss. These tumors appear highly sensitive to abiraterone treatment. Clin Cancer Res; 24(22); 5585-93. ©2018 AACR.

Advances in Silver Nanotechnology: An Update on Biomedical Applications and Future Perspectives.

Nanotechnology is one of the most promising fields for producing new applications in nanotechnology, biotechnology, and medicine. However, only a few products have been used for nanotechnology, biotechnology, and medical purposes. Nanoparticles have been among the most usually applied nanomaterial in our health care system for hundreds of years. The most prominent nano product is nano silver which generally present at 1-100 nm in size in at least one dimension. Silver nanoparticles reveal remarkably unusual chemical, physical and biological properties and have been used for many different applications which detailed in this review. This review is focusing on the different form of silver nanoparticles and its nanotechnological, biotechnological and medical applications.

The potential of nanofibers in tissue engineering and stem cell therapy.

Electrospinning is a technique in which materials in solution are shaped into continuous nano- and micro-sized fibers. Combining stem cells with biomaterial scaffolds and nanofibers affords a favorable approach for bone tissue engineering, stem cell growth and transfer, ocular surface reconstruction, and treatment of congenital corneal diseases. This review seeks to describe the current examples of the use of scaffolds in stem cell therapy. Stem cells are classified as adult or embryonic stem (ES) cells, and the advantages and drawbacks of each group are detailed. The nanofibers and scaffolds are further classified in Tables I and II , which describe specific examples from the literature. Finally, the current applications of biomaterial scaffolds containing stem cells for tissue engineering applications are presented. Overall, this review seeks to give an overview of the biomaterials available for use in combination with stem cells, and the application of nanofibers in stem cell therapy.

Recent prospective of nanofiber scaffolds fabrication approaches for skin regeneration.

The largest organ of human body is skin, which acting as a barrier with immunologic, sensorial and protective functions. It is always in exposure to the external environment, which can result many different types of damage and injury with loss of variable volumes of extracellular matrix (ECM). For the treatment of skin lesions and damages, several approaches are now accessible, such as the application of allografts, autografts, and tissue-engineered substitutes, wound dressings and nanofiber scaffolds approaches. Even though proven clinically effective, these methods are still characterized by main drawbacks such as patient inadequate vascularization, morbidity, the inability to reproduce skin appendages, low adherence to the wound bed and high manufacturing costs. Advanced approaches based on nanofiber scaffolds approaches offer a permanent, viable and effective substitute to explain the drawbacks of skin regeneration and repair by combining growth factors, cells, and biomaterials and advanced biomanufacturing methods. This review details recent advances of nanofiber scaffolds in skin regeneration and repair strategies, and describes a synthesis method of nanofiber scaffolds.

Effect of preheating of low shrinking resin composite on intrapulpal temperature and microtensile bond strength to dentin.

The effect of preheating of the silorane-based resin composite on intrapulpal temperature (IPT) and dentin microtensile bond strength (µTBS) was evaluated. For the IPT, teeth (n = 15) were sectioned to obtain discs of 0.5 mm thickness (2 discs/tooth). The discs were divided into three groups (n = 10/group) according to the temperature of the Filtek LS™ silorane-based resin composite during its placement, either at room temperature (23 ± 1 °C) or preheated to 54 °C or 68 °C using a commercial Calset™ device. Discs were subjected to a simulated intrapulpal pressure (IPP) and placed inside a specially constructed incubator adjusted at 37 °C. IPT was measured before, during and after placement and curing of the resin composite using K-type thermocouple. For µTBS testing, flat occlusal middentin surfaces (n = 24) were obtained. P90 System Adhesive was applied according to manufacturer's instructions then Filtek LS was placed at the tested temperatures (n = 6). Restorative procedures were done while the specimens were connected to IPP simulation. IPP was maintained and the specimens were immersed in artificial saliva at 37 °C for 24 h before testing. Each specimen was sectioned into sticks (0.9 ± 0.01 mm(2)). The sticks (24/group) were subjected to µTBS test and their modes of failure were determined using scanning electron microscope (SEM). For both preheated groups, IPT increased equally by 1.5-2 °C upon application of the composite. After light curing, IPT increased by 4-5 °C in all tested groups. Nevertheless, the IPT of the preheated groups required a longer time to return to the baseline temperature. One-way ANOVA revealed no significant difference between the µTBS values of all groups. SEM revealed predominately mixed mode of failure. Preheating of silorane-based resin composite increased the IPT but not to the critical level and had no effect on dentin µTBS.