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Background: Management of dementia involves a multidisciplinary approach which also requires active participation from family members and caregivers. Thus, having easy access to information about dementia care is pertinent. Internet-based information is an emerging method for the same., Aim: To perform a comparative assessment of patient-oriented online information available on treatment of dementia over web pages in English and Hindi language., Methods: Observational study was conducted online through a general internet search engine (www.google.com). Web pages containing patient-oriented online information on treatment of dementia in English and Hindi were reviewed to assess their content and quality, esthetics, and interactivity. Appropriate descriptive and inferential statistics were conducted using the Statistical Package for the Social Sciences., Results: A total of 70 web pages met the eligibility criteria. Content quality assessed using the DISCERN score was significantly higher for English web pages compared to Hindi web pages ( P < 0.01). About 72.4% (21/29) of English and only 9.8% (4/41) of Hindi web pages had a total DISCERN score of 40 or above, indicating good quality. For esthetics, the median score for English pages was significantly higher than for Hindi web pages ( P < 0.01). The web pages with Health On Net (HON) certification had significantly better content quality., Conclusion: Our study revealed a scarcity of good quality online information about dementia and its treatment, especially in the Hindi language. English language websites showed better content quality than Hindi websites. HON Code label might be used as an indicator of better content quality for online resources informing on dementia treatment by lay people., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Psychiatry.)

Background: Pain and depression are associated, but it is uncertain if effective pain relief during labor by labor analgesia reduces the incidence of postpartum depression (PPD). This randomized, controlled study assessed whether combined spinal-epidural (CSE) labor analgesia is associated with a decreased risk of PPD. Other reported risk factors for PPD were also assessed., Materials and Methods: Parturients were randomly assigned to either CSE labor analgesia or normal vaginal delivery ( n = 65 each). CSE parturients received 0.5 ml of 0.5% hyperbaric bupivacaine intrathecally and PCEA with continuous infusion of 0.1% levobupivacaine and 2 μg/ml fentanyl @5 ml/h along with patient-controlled boluses with a lockout interval of 15 min. Parturients of both the groups were assessed using Edinburgh Postnatal Depression Scale (EPDS) for depressive symptoms at day 3 and PPD at 6 weeks (primary outcome; defined as EPDS score ≥10 at 6 weeks postpartum). Secondary outcomes included pain scores, maternal satisfaction, and Apgar scores at 1 and 5 min. Parturients were also screened for several risk factors for PPD., Results: Incidence of PPD was 22.3%. The difference in incidence of PPD between the CSE group vs. control group was not significant (27.7% vs. 16.9%; Fisher's exact P = 0.103). Of all the risk factors analyzed in logistic regression model, perceived stress during pregnancy was the only significant predictor of the development of PPD (adjusted Odds Ratio 11.17, 95% Confidence interval 2.86-43.55; P = 0.001)., Conclusion: CSE analgesia in laboring parturients does not reduce PPD at 6 weeks. Instead, perceived high stress during pregnancy appears to be the most important factor., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Saudi Journal of Anesthesia.)

Background & Aims: Abnormal iron metabolism and hepatic iron-overload is a major cause of liver injury and in the development of chronic liver diseases. Iron-overload-mediated liver disease leads to end-stage cirrhosis and/or hepatocellular carcinoma., Methods: Using a genetic hemochromatosis (hemojuvelin knockout mice) and non-genetic (secondary iron-overload) murine models of hepatic iron-overload, we elucidated the mechanism of hepatic iron injury and the therapeutic effects of resveratrol., Results: Hepatic iron-overload was associated with hepatosplenomegaly, increased oxidative stress, hepatic fibrosis, and inflammation, and a pro-apoptotic state which was markedly corrected by resveratrol therapy. Importantly our aging studies with the hemojuvelin knockout mice showed advanced liver disease in association with steatosis in the absence of a diabetic state which recapitulates the essential pathological features seen in clinical iron-overload. Chronic hepatic iron-overload showed increased nuclear localization of acetylated Forkhead fox-O-1 (FoxO1) transcription factor whereas resveratrol dietary intervention reversed the acetylation of FoxO1 in association with increased SIRT1 levels which together with its pleotropic antioxidant properties are likely key mechanisms of its therapeutic action. Importantly, resveratrol treatment did not affect the degree of hepatic iron-overload but rather direct protects the liver from iron-mediated injury., Conclusions: Our findings illustrate a novel and definitive therapeutic action of resveratrol and represent an economically feasible therapeutic intervention to treat hepatic iron-overload and liver disease., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Unlabelled: Activation of the angiotensin 1-7/Mas receptor (MasR) axis counteracts angiotensin II (Ang II)-mediated cardiovascular disease. Recombinant human angiotensin-converting enzyme 2 (rhACE2) generates Ang 1-7 from Ang II. We hypothesized that the therapeutic effects of rhACE2 are dependent on Ang 1-7 action. Wild type male C57BL/6 mice (10-12 weeks old) were infused with Ang II (1.5 mg/kg/d) and treated with rhACE2 (2 mg/kg/d). The Ang 1-7 antagonist, A779 (200 ng/kg/min), was administered to a parallel group of mice. rhACE2 prevented Ang II-induced hypertrophy and diastolic dysfunction while A779 prevented these beneficial effects and precipitated systolic dysfunction. rhACE2 effectively antagonized Ang II-mediated myocardial fibrosis which was dependent on the action of Ang 1-7. Myocardial oxidative stress and matrix metalloproteinase 2 activity was further increased by Ang 1-7 inhibition even in the presence of rhACE2. Activation of Akt and endothelial nitric oxide synthase (eNOS) by rhACE2 were suppressed by the antagonism of Ang 1-7 while the activation of pathological signaling pathways was maintained. Blocking Ang 1-7 action prevents the therapeutic effects of rhACE2 in the setting of elevated Ang II culminating in systolic dysfunction. These results highlight a key cardioprotective role of Ang 1-7, and increased Ang 1-7 action represents a potential therapeutic strategy for cardiovascular diseases., Key Messages: Activation of the renin-angiotensin system (RAS) plays a key pathogenic role in cardiovascular disease. ACE2, a monocarboxypeptidase, negatively regulates pathological effects of Ang II. Antagonizing Ang 1-7 prevents the therapeutic effects of recombinant human ACE2. Our results highlight a key protective role of Ang 1-7 in cardiovascular disease.

Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of matrix metalloproteinases (MMPs). While TIMP2 and TIMP3 inhibit MMPs, TIMP3 also inhibits activation of pro-MMP2, whereas TIMP2 promotes it. Here we assessed the differential role of TIMP2 and TIMP3 in renal injury using the unilateral ureteral obstruction model. Gene microarray assay showed that post obstruction, the lack of TIMP3 had a greater impact on gene expression of intermediate, late injury- and repair-induced transcripts, kidney selective transcripts, and solute carriers. Renal injury in TIMP3(-/-), but not in TIMP2(-/-), mice increased the expression of collagen type I/III, connective tissue growth factor, transforming growth factor-β, and the downstream Smad2/3 pathway. Interestingly, ureteral obstruction markedly increased MMP2 activation in the kidneys of TIMP3(-/-) mice, which was completely blocked in the kidneys of TIMP2(-/-) mice. These changes are consistent with enhanced renal tubulointerstitial fibrosis in TIMP3(-/-) and its reduction in TIMP2(-/-) mice. The activities of tumor necrosis factor-α-converting enzyme, caspase-3, and mitogen-activated kinases were elevated in the kidneys of TIMP3(-/-) mice but not TIMP2(-/-) mice, suggesting enhanced activation of apoptotic and pathological signaling pathways only in the obstructed kidney of TIMP3(-/-) mice. Thus, TIMP2 and TIMP3 play differential and contrasting roles in renal injury: TIMP3 protects from damage, whereas TIMP2 promotes injury through MMP2 activation.

Rationale: The classic phagocyte nicotinamide adenine dinucleotide phosphate oxidase (gp91(phox) or Nox2) is expressed in the heart. Nox2 activation requires membrane translocation of the p47(phox) subunit and is linked to heart failure. We hypothesized that loss of p47(phox) subunit will result in decreased reactive oxygen species production and resistance to heart failure., Objective: To define the role of p47(phox) in pressure overload-induced biomechanical stress., Methods and Results: Eight-week-old male p47(phox) null (p47(phox) knockout [KO]), Nox2 null (Nox2KO), and wild-type mice were subjected to transverse aortic constriction-induced pressure overload. Contrary to our hypothesis, p47(phox)KO mice showed markedly worsened systolic dysfunction in response to pressure overload at 5 and 9 weeks after transverse aortic constriction compared with wild-type-transverse aortic constriction mice. We found that biomechanical stress upregulated N-cadherin and β-catenin in p47(phox)KO hearts but disrupted the actin filament cytoskeleton and reduced phosphorylation of focal adhesion kinase. p47(phox) interacts with cytosolic cortactin by coimmunoprecipitation and double immunofluorescence staining in murine and human hearts and translocated to the membrane on biomechanical stress where cortactin interacted with N-cadherin, resulting in adaptive cytoskeletal remodeling. However, p47(phox)KO hearts showed impaired interaction of cortactin with N-cadherin, resulting in loss of biomechanical stress-induced actin polymerization and cytoskeletal remodeling. In contrast, Nox2 does not interact with cortactin, and Nox2-deficient hearts were protected from pressure overload-induced adverse myocardial and intracellular cytoskeletal remodeling., Conclusions: We showed a novel role of p47(phox) subunit beyond and independent of nicotinamide adenine dinucleotide phosphate oxidase activity as a regulator of cortactin and adaptive cytoskeletal remodeling, leading to a paradoxically enhanced susceptibility to biomechanical stress and heart failure.

Aortic aneurysm is dilation of the aorta primarily due to degradation of the aortic wall extracellular matrix (ECM). Tissue inhibitors of metalloproteinases (TIMPs) inhibit matrix metalloproteinases (MMPs), the proteases that degrade the ECM. Timp3 is the only ECM-bound Timp, and its levels are altered in the aorta from patients with abdominal aortic aneurysm (AAA). We investigated the causal role of Timp3 in AAA formation. Infusion of angiotensin II (Ang II) using micro-osmotic (Alzet) pumps in Timp3(-/-) male mice, but not in wild type control mice, led to adverse remodeling of the abdominal aorta, reduced collagen and elastin proteins but not mRNA, and elevated proteolytic activities, suggesting excess protein degradation within 2 weeks that led to formation of AAA by 4 weeks. Intriguingly, despite early up-regulation of MMP2 in Timp3(-/-)Ang II aortas, additional deletion of Mmp2 in these mice (Timp3(-/-)/Mmp2(-/-)) resulted in exacerbated AAA, compromised survival due to aortic rupture, and inflammation in the abdominal aorta. Reconstitution of WT bone marrow in Timp3(-/-)/Mmp2(-/-) mice reduced inflammation and prevented AAA in these animals following Ang II infusion. Treatment with a broad spectrum MMP inhibitor (PD166793) prevented the Ang II-induced AAA in Timp3(-/-) and Timp3(-/-)/Mmp2(-/-) mice. Our study demonstrates that the regulatory function of TIMP3 is critical in preventing adverse vascular remodeling and AAA. Hence, replenishing TIMP3, a physiological inhibitor of a number of metalloproteinases, could serve as a therapeutic approach in limiting AAA development or expansion.