Antidepressant effect on connectivity of the mood-regulating circuit: an FMRI study.

The mechanisms by which antidepressant-induced neurochemical changes lead to physiological changes in brain circuitry and ultimately an antidepressant response remain unclear. This study investigated the effects of sertraline, a selective serotonin reuptake inhibitor antidepressant, on corticolimbic connectivity, using functional magnetic resonance imaging (fMRI). In all, 12 unmedicated unipolar depressed patients and 11 closely matched healthy control subjects completed two fMRI scanning sessions at baseline and after 6 weeks. Depressed patients received treatment with sertraline between the two sessions. During each fMRI session, subjects first completed a conventional block-design experiment. Next, connectivity between cortical and limbic regions was measured using correlations of low-frequency blood oxygen level-dependent (BOLD) fluctuations (LFBF) during continuous exposure to neutral, positive, and negative pictures. At baseline, depressed patients had decreased corticolimbic LFBF correlations compared to healthy subjects during the resting state and on exposure to emotionally valenced pictures. At rest and on exposure to neutral and positive pictures, LFBF correlation between the anterior cingulate cortex and limbic regions was significantly increased in patients after treatment. However, on exposure to negative pictures, corticolimbic LFBF correlations remained decreased in depressed patients. The results of this study are consistent with the hypothesis that antidepressant treatment may increase corticolimbic connectivity, thereby possibly increasing the regulatory influence of cortical mood-regulating regions over limbic regions.     

Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial.

PURPOSE: Biliary cancer has a poor prognosis, and chemotherapy has had little impact. The objectives of this trial were to determine the response rate, time to disease progression, survival, and safety profile of the combination of gemcitabine and capecitabine (GemCap) in patients with advanced biliary cancer. PATIENTS AND METHODS: Eligible patients had pathologically proven, locally advanced or metastatic adenocarcinoma arising from the intra- and extrahepatic bile ducts or gallbladder with no prior chemotherapy. Patients were treated on a 3-week cycle consisting of capecitabine at 650 mg/m(2) orally twice a day for 14 days and gemcitabine at a fixed dose of 1,000 mg/m(2) intravenously over 30 minutes on days 1 and 8. RESULTS: Forty-five patients were enrolled between July 2001 and January 2004. Fifty-three percent of patients had cholangiocarcinoma, 47% had gallbladder cancer, and 89% had metastatic disease. The overall objective response rate was 31%, with an additional 42% of patients with stable disease, for a disease control rate of 73%. The median overall survival time was 14 months (95% CI, 7.3 months to not available), and the median progression-free survival time was 7 months (95% CI, 4.6 to 11.8 months). This chemotherapy combination was generally well tolerated. Transient neutropenia, thrombocytopenia, fatigue, and hand-foot syndrome were commonly observed but were easily managed without discontinuing further treatment. CONCLUSION: The significant antitumor activity combined with a mild toxicity profile seen in this study argue that GemCap chemotherapy may benefit patients with advanced biliary cancer. This regimen warrants further evaluation in a randomized study with survival and quality of life end points.     

Evidence for selective expression of the p53 codon 72 polymorphs: implications in cancer development.

Polymorphism at codon 72 of p53 results in either the arginine or proline form of p53, whose functional significance in carcinogenesis is controversial. We have investigated if the expression of these p53 polymorphs is selectively regulated, using mRNA from peripheral blood of healthy Asian (Chinese) and the Caucasian (Polish) arginine/proline (arg/pro) heterozygote subjects. Asians were found to preferentially express the pro allele whereas the Caucasians preferentially express the arg allele. On the contrary, about 75% of the heterozygote Chinese breast cancer patients preferentially expressed the arg allele, which rarely contained any somatic mutations. Moreover, histologically normal tissues from Chinese heterozygote breast cancer patients showed selective expression of the arg allele, in contrast to the preferential expression of the pro allele in heterozygote healthy normal breast tissues. Together, the data suggest that the expression of the different p53 polymorphs is selectively regulated in different ethnic populations, and that the arg allele is activated during cancer development in Asians. Thus, the expression status of the p53 polymorphs, rather than the genotypic status, might be a useful indicator for cancer susceptibility.     

Congenital Hyperinsulinemic Hypoglycemia and Hyperammonemia due to Pathogenic Variants in GLUD1

Indian Journal of Pediatrics - Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disorder, characterized by dysregulated insulin secretion. Pathogenic variants in at...     

Tribological Performance of High-Entropy Coatings (HECs): A Review

Surface coatings that operate effectively at elevated temperatures provide compatibility with critical service conditions as well as improved tribological performance of the components. High-entropy coatings (HECs), including metallic, ceramics, and composites, have gained attention all over the world and developed rapidly over the past 18 years, due to their excellent mechanical and tribological properties. High-entropy alloys (HEAs) are defined as alloys containing five or more principal elements in equal or close to equal atomic percentage. Owing to the high configurational entropy compared to conventional alloys, HEAs are usually composed of a simple solid solution phase, such as the BCC and FCC phases, instead of complex, brittle intermetallic phases. Several researchers have investigated the mechanical, oxidation, corrosion and wear properties of high-entropy oxides, carbides, borides, and silicates using various coating and testing techniques. More recently, the friction and wear characteristics of high-entropy coatings (HECs) have gained interest within various industrial sectors, mainly due to their favourable mechanical and tribological properties at high temperatures. In this review article, the authors identified the research studies and developments in high-entropy coatings (HECs) fabricated on various substrate materials using different synthesis methods. In addition, the current understanding of the HECs characteristics is critically reviewed, including the fabrication routes of targets/feedstock, synthesis methods utilized in various research studies, microstructural and tribological behaviour from room temperature to high temperatures.     

The Effect of Customized and Silicon Insoles on Mid- and Hindfoot in Adult Flexible Pes Planovalgus

BackgroundFlexible flat foot or pes planovalgus is a common foot deformity, and silicone and customized insole are commonly used as a non-operative treatment modality of flexible planovalgus. However, there are inadequate data and limited evidence available regarding the immediate effects of their use in midfoot and hindfoot of adults. The aim of this study is to quantify and compare the radiological parameters immediately on weightbearing with silicon and customized insoles and without them to assess the effect on midfoot and hindfoot of the flexible planovalgus in adults.MethodsA total number of 11 (8 females and 3 males) subjects with flexible pes planovalgus deformity without any other foot deformity were included in the study. Each patient was assessed three times in a random sequence without and with use of either silicon insoles or customized insole. The radiographic parameters without insole, with silicon insole, and with customized insole conditions were calculated using online available computer software Kinovea.ResultsOne-way ANOVA analysis was performed between groups (without insole, with silicone insole and with customized insole). The hindfoot parameters depicted that calcaneal inclination angle (CIA) was significant increased (P = 0.000) and talar declination angle (TDA) was significantly decreased (P = 0.003) only with the use of customized insole compared to without insole. The midfoot parameters depicted that the first metatarsal angle (FMA) and talonavicular coverage angle (TCA) were significantly lower with customized insole (P = 0.00) as compared to other two groups and significantly lower with silicone insole (P = 0.00) as compared to without insole group.ConclusionThe results imply that the compressibility of the insole material affects the forefoot and hindfoot biomechanics differently. This study concludes that silicone insole affects only the midfoot which bears 45% of bodyweight and customized insole affects both midfoot and more importantly the hindfoot which bears 55% of bodyweight.     

Development,optimization and characterization of glycyrrhetinic acid–chitosan nanoparticles of atorvastatin for liver targeting

Glycyrrhetinic acid-modified chitosan (mGA-suc-CTS) is used as liver-targeted carrier for drug delivery. In this study, nanoparticles were prepared by ionic gelation process, and glycyrrhetinic acid act as the targeting ligand. The structure of the product was confirmed by IR and NMR techniques. The main aim of this study was to deliver atorvastatin directly to the liver by using same conjugate and reduce the associated side-effects, i.e. hepatotoxicity at high dose. Characterization of the developed formulation was performed by differential scanning calorimetry, particle size measurements and cellular uptake studies. Release profile, pharmacokinetics studies and organ distribution studies showed that developed formulation shows a relative higher liver uptake. The optimized formulation showed increased plasma concentration than the CTS nanoparticles as well as plain drug and the accumulation in the liver was nearly 2.59 times more than that of obtained with the CTS nanoparticles. Pharmaceutical and pharmacological indicators suggested that the proposed strategy can be successfully utilized for liver targeting of therapeutics.     

Utility of prolonged bedside amplitude-integrated encephalogram in encephalopathic infants

We hypothesized that prolonged bedside limited-channel amplitude-integrated electroencephalogram (aEEG) monitoring following a standard 1-hour conventional electroencephalogram (cEEG) would increase the detection of subclinical seizures and allow continuous evaluation of the background EEG in neonatal encephalopathy. This may identify complementary roles for these EEG technologies in neonatal units where continuous cEEG monitoring may not be readily available. We prospectively recruited 25 term neonates with a diagnosis of neonatal seizures or encephalopathy. All infants underwent a standard 1-hour cEEG followed by 12 to 24 hours of aEEG monitoring. Data from the aEEG (plus the raw signal) were analyzed by an epileptologist and compared with information obtained from the clinical report of the cEEG. aEEG and cEEG data were available for 24 infants. Results from magnetic resonance imaging (MRI) performed at 7 to 10 days of life were available in 23/24 infants. Background classification on cEEG and aEEG was similar in 83% of patients. Five of 24 infants had normal background on cEEG. Prolonged aEEG detected evolution of background from initially normal to moderately abnormal in an additional four infants. It also detected more subclinical seizures than the 1-hour cEEG in 8/14 infants. Normal background on aEEG and cEEG was associated with normal MRI results, and severe background abnormality (5/24) on both aEEG and cEEG was associated with abnormal MRI results. Data obtained from prolonged aEEG (plus raw EEG) provide similar background activity, enhance seizure detection, and complement standard cEEG in predicting short-term outcomes, based on MRI, in term neonates with seizures or encephalopathy. Limited-channel aEEG technology may provide a pragmatic alternative for longitudinal monitoring of newborn infants with encephalopathy in neonatal units where prolonged video EEG monitoring is not feasible.