Genotype correlates with clinical course and outcome of children with tight junction protein 2 (TJP2) deficiency-related cholestasis.

BACKGROUND AND AIMS: The study aimed to describe the clinical course and outcomes, and analyze the genotype-phenotype correlation in patients with tight junction protein 2 (TJP2) deficiency. APPROACH AND RESULTS: Data from all children with chronic cholestasis and either homozygous or compound heterozygous mutations in TJP2 were extracted and analyzed. The patients were categorized into 3 genotypes: TJP2-A (missense mutations on both alleles), TJP2-B (missense mutation on one allele and a predicted protein-truncating mutation [PPTM] on the other), and TJP2-C (PPTMs on both alleles). A total of 278 cases of genetic intrahepatic cholestasis were studied, with TJP2 deficiency accounting for 44 cases (15.8%). Of these, 29 were homozygous and 15 were compound heterozygous variants of TJP2 . TJP2-A genotype was identified in 21 (47.7%), TJP2-B in 7 cases (15.9%), and TJP2-C in 16 cases (36.4%), respectively. Patients with the TJP2-C genotype were more likely to experience early infantile cholestasis (87.5% vs. 53.5%, p =0.033), less likely to clear jaundice (12.5% vs. 52.2%, p =0.037), more likely to develop ascites, and had higher serum bile acids. Patients with the TJP2-C genotype were more likely to die or require liver transplantation (native liver survival: 12.5% vs. 78.6%, p <0.001), with a median age at death/liver transplantation of 2.5 years. Cox regression analysis revealed that TJP2-C mutations ( p =0.003) and failure to resolve jaundice ( p =0.049) were independent predictors of poor outcomes. CONCLUSIONS: Patients with the TJP2-C genotype carrying PPTMs in both alleles had a rapidly progressive course, leading to early decompensation and death if they did not receive timely liver transplantation.

Surgical and Survival Outcomes of Operable Gastric Cancer-Experience from a Tertiary Care Center in South India.

Gastric cancer is one of the leading cancers in Southern India. Data regarding the gastric cancers among the Indian population is sparse. Most patients in our country have locally advanced gastric cancers due to delayed presentation. In this article, we present our data regarding the presentation patterns, epidemiological demographics, surgical outcomes, and survival patterns from a tertiary care center in South India. This is a retrospective analysis of gastric cancer patients who underwent gastrectomy in our institution between January 2015 and November 2021 (n = 102). The data regarding patient characteristics, histopathology, and perioperative outcomes were analysed from medical records. The adjuvant treatment received and survival details were collected from the follow-up records and by telephonic interviews. A total of 128 patients were assessable, 102 patients underwent gastrectomy in a period of 6 years. The median age of presentation was 60 years and males were more commonly affected (70.6%). Most common presentation was pain abdomen followed by gastric outlet obstruction. Adenocarcinoma NOS (93%) was the most common histological type. Most of the Patients had antropyloric growths (79.4%) and subtotal gastrectomy with D2 lymphadenectomy was the most common surgery performed. Majority of the tumors were T4 tumors (55.9%) and nodal metastases were detected in 74% of the specimens. Predominant morbidity was wound infection (6.1%) followed by anastomotic leak (5.9%) with a combined overall morbidity of 16.7% and 30-day mortality of 2.9%. Seventy five (80.5%) patients were able to complete all planned 6 cycles of adjuvant chemotherapy. The median time of survival calculated by Kaplan-Meier method was 23 months with 2-year and 3-year overall survival rates of 31% and 22%, respectively. Lymphovascular invasion (LVSI) and lymph nodal burden were the risk factors associated with recurrences and deaths. The patient characteristics, histological factors, and perioperative outcomes revealed most of our patients presented in locally advanced stages with poor risk histological types and increased nodal burden contributing to the lower survival in our population. Inferior survival outcomes suggest the need to explore perioperative and neoadjuvant chemotherapy options in our population.

Clinical relevance of double-arm blood pressure measurement and prevalence of clinically important inter-arm blood pressure differences in Indian Primary Care.

Hypertension guidelines recommend measuring blood pressure (BP) in both arms at least once. However, this is seldom done due to uncertainties regarding measurement procedure and the implications of finding a clinically important inter-arm BP difference (IAD). This study aimed to provide insight into the prevalence of clinically important IADs in a large Indian primary care cohort. A number of 134678 (37% female) unselected Indian primary care participants, mean age 45.2 (SD 11.9) years, had BP measured in both arms using a standardized, triplicate, automated simultaneous measurement method (Microlife WatchBP Office Afib). On average, there were clinically minor differences in right and left arm BP values: systolic BP 134.4 vs. 134.2 mmHg (p<0.01) and diastolic BP 82.7 vs. 82.6 mmHg (p<0.01), respectively. Prevalence of significant mean systolic IAD between 10 and 15 mmHg was 7813 (5.8%). Systolic IAD ≥ 15 mmHg 2980 (2.2%) and diastolic IAD ≥ 10 mmHg 7151 (5.3%). In total, there were 7595 (5.6%) and 8548 (6.3%) participants with BP above the 140/90 mmHg threshold in only the left or right arm, respectively. Prevalence of participants with elevated BP on one arm only was highest in patients with a systolic IAD ≥ 15 mmHg; 19.1% and 13.7%, for left and right arm, respectively. This study shows that a substantial prevalence of IAD exist in Indian primary care patients. BP is above the diagnostic threshold for hypertension in one arm only for 6% of participants. These findings emphasise the importance of undertaking bilateral BP measurement in routine clinical practice. This article is protected by copyright. All rights reserved.

Clinical relevance of double-arm blood pressure measurement and prevalence of clinically important inter-arm blood pressure differences in Indian primary care.

Hypertension guidelines recommend measuring blood pressure (BP) in both arms at least once. However, this is seldom done due to uncertainties regarding measurement procedure and the implications of finding a clinically important inter-arm BP difference (IAD). This study aimed to provide insight into the prevalence of clinically important IADs in a large Indian primary care cohort. A number of 134 678 (37% female) unselected Indian primary care participants, mean age 45.2 (SD 11.9) years, had BP measured in both arms using a standardized, triplicate, automated simultaneous measurement method (Microlife WatchBP Office Afib). On average, there were clinically minor differences in right and left arm BP values: systolic BP 134.4 vs 134.2 mmHg (p < .01) and diastolic BP 82.7 vs 82.6 mmHg (p < .01), respectively. Prevalence of significant mean systolic IAD between 10 and 15 mmHg was 7,813 (5.8%). Systolic IAD ≥ 15 mmHg 2,980 (2.2%) and diastolic IAD ≥ 10 mmHg 7,151 (5.3%). In total, there were 7,595 (5.6%) and 8,548 (6.3%) participants with BP above the 140/90 mmHg threshold in only the left or right arm, respectively. Prevalence of participants with elevated BP on one arm only was highest in patients with a systolic IAD ≥ 15 mmHg; 19.1% and 13.7%, for left and right arm, respectively. This study shows that a substantial prevalence of IAD exists in Indian primary care patients. BP is above the diagnostic threshold for hypertension in one arm only for 6% of participants. These findings emphasize the importance of undertaking bilateral BP measurement in routine clinical practice.

Blood pressure and heart rate related to sex in untreated subjects: the India ABPM study.

Women are underrepresented in groups of patients seeking hypertension care in India. The present paper reports trends in office and ambulatory blood pressure measurement (OBPM, ABPM) and 24-h heart rate (HR) with sex in 14,977 subjects untreated for hypertension (aged 47.3 ± 13.9 years, males 69.4%) visiting primary care physicians. Results showed that, for systolic blood pressure (SBP), females had lower daytime ABPM (131 ± 16 vs. 133 ± 14 mm Hg, P < .001) but higher nighttime ABPM (122 ± 18 vs. 121 ± 16 mm Hg, P < .001) than males. Females had higher HR than men at daytime (80 ± 11 vs 79 ± 11.5 bpm) and nighttime (71 ± 11 vs 69 ± 11), respectively (all P < .001). Dipping percentages for SBP (7.4 ± 7.3 vs 9.3 ± 7.4%), DBP (10.1 ± 8.6 vs. 12.3 ± 8.9%), and HR (10.7 ± 7.9 vs. 12.8 ± 9.2%) were lower (P < .001) for females than for males, respectively. Females more often had isolated nighttime hypertension as compared to males (14.9%, n = 684% vs 10.6%, n = 1105; P < .001). BP patterns and HR showed clear differences in sex, particularly at nighttime. As females were more often affected by non-dipping and elevated nighttime SBP and HR than males, they should receive ABPM, at least, as frequently as men to document higher risk necessitating treatment.

Oncological Outcomes After Radical Esophagectomy from a Tertiary Cancer Center.

Although esophageal cancers have poor survival outcomes, evidence suggests that preoperative chemoradiation followed by surgery have improved survival outcomes. Minimally invasive surgery has equivalent oncological outcomes with less complication compared with open surgery, but there is insufficient data available in South Indian population. Our aim was to analyze the perioperative outcome and survival between minimally invasive and open transhiatal esophagectomy group. Data from patients operated for esophageal cancer in our department from the year 2015 to 2018 were collected retrospectively using medical records. Among 55 carcinoma esophagus patients, squamous histology (67%) and lower third location (57%) being predominant. Twenty-six patients underwent video-assisted thoracoscopic surgery (VATS)-assisted esophagectomy and 18 patients underwent open transhiatal esophagectomy. Eleven patients were inoperable. Sixteen patients in VATS arm and three patients in transhiatal arm received preoperative chemoradiation. VATS arm has lesser intraoperative blood loss, early pulmonary recovery with early intercostal drain removal, and lesser hospital stay but longer mean operating time of 171 min versus 140 min (P < 0.01). It has higher mean nodal harvest of 15 versus 7 nodes (P 0.01) and higher overall median survival of 36 months (95% CI, 29.3 to 42.7) as against 23 months (95% CI, 17.8 to 29.2) for transhiatal arm (P < 0.01). VATS-assisted esophagectomy is less morbid procedure with early postoperative recovery, better oncological outcomes, and improved survival compared with transhiatal arm which is equivalent to apex centers in India.

Therapeutic Enteral Formulas in Children.

PURPOSE: A variety of enteral formulas for various diseases have become available in India in the last few years. Awareness among pediatricians about the availability and indications for these therapeutic formulas is low. METHODS: A literature search was conducted in PUBMED and relevant data collected from all English language publications available. Data on the commercial preparations was sourced from the individual companies, the Diet 4 life initiative as well as FSSAI (Food safety and standards authority of India). CONCLUSIONS: Therapeutic enteral formulas, which are indicated in various disease states belong to four categories - lactose modified, hydrolyzed, MCT based and metabolic disease specific formulas. Lactose modified formulas which are used in temporary or permanent lactose intolerance and Galactosemia are either casein or soy protein based. Hydrolyzed formulas could be partially hydrolyzed, extensively hydrolyzed or amino acid based. Only extensively hydrolyzed formula should be recommended in milk protein allergy. Amino acid (elemental) formulas are mainly indicated in patients with diffuse intestinal mucosal disease. MCT formulas are used in chronic liver disease with cholestasis, and have 30 to 80% MCT. Formulas for inborn errors of metabolism are free of specific carbohydrate, amino acid or fatty acid. Proprietary formulas presently available in India with their specifications have been listed.

Outbreaks of Salmonella illness associated with frozen raw breaded chicken products in Canada, 2015-2019.

Frozen raw breaded chicken products (FRBCP) have been identified as a risk factor for Salmonella infection in Canada. In 2017, Canada implemented whole genome sequencing (WGS) for clinical and non-clinical Salmonella isolates, which increased understanding of the relatedness of Salmonella isolates, resulting in an increased number of Salmonella outbreak investigations. A total of 18 outbreaks and 584 laboratory-confirmed cases have been associated with FRBCP or chicken since 2017. The introduction of WGS provided the evidence needed to support a new requirement to control the risk of Salmonella in FRBCP produced for retail sale.

Insights on the Jahn-Teller distortion, hydrogen bonding and local-environment correlations in a promised multiferroic hybrid perovskite.

Perovskite-type formates have recently emerged as potential candidates for multiferroics. Previous ab initio calculations have concluded that copper guanidinium formate (CuGF) is a promising multiferroic. Although ab initio design and characterisation of inorganic multiferroics is at a mature stage, this situation is not true for multiferroic metal-organic frameworks. Regardless of these limitations, such predictions have also been extended to other materials. Here, we present with deeper insights into the structural aspects based on single crystal neutron diffraction studies, questioning such predictions in CuGF. The comparative investigation of the polar CuGF and its centrosymmetric cousin, MnGF, uncovers the differences in the N-H⋯O bonds. Such differences are associated with the Jahn-Teller distortion, which balances its influence on the local-environment of the three sets of ND2 in the guanidinium cation. Hydrogen bonds which were not dealt with in the previous ab initio studies have been carefully treated in this experimental study. Hence, providing a crucial understanding based on which an encouraging platform may be rendered for improving the ab initio calculations for hybrid perovskites catering various applications.

The Effect of Surface Treatments on the Shear Bond Strength of Acrylic Resin Denture Base With Different Repair Acrylic Resin: An In Vitro Study.

BACKGROUND: Fracture of the denture base is a common problem associated with dental prostheses. Fractured denture base surfaces treated with chemical agents and mechanical features have the potential for improved bond strength. AIM: The aim of this study was to evaluate the effect of surface treatment on the shear bond strength of heat-cured denture base with different repair acrylic resins. MATERIALS AND METHODS: A total of 100 circular specimens (2-cm diameter × 3.3-mm thickness) were fabricated from heat-cured denture resins (DPI) according to the manufacturer's instructions. The heat-cured denture base acrylic resin specimens were divided into two groups: In group 1, auto-polymerizing acrylic resin (DPI) was used as a repair resin, and in group 2, light-cured acrylic resin (VLC) was used as the repair resin. Further, the heat-cured denture base acrylic resin specimens were subdivided into five subgroups. The shear bond strength (in megapascal) was measured in a universal testing machine at a crosshead speed of 1 mm/min. The results were subjected for statistical analysis. RESULT: Comparison of mean and standard deviation of shear bond strength between DPI and VLC group using one-way analysis of variance showed that the mean shear bond strength of DPI group is higher than that of VLC group. CONCLUSION: From the study, heat-cured denture base specimens repaired with auto-polymerizing repair resin showed higher mean shear bond strength than the visible light cure resin material.

Disorder in the hydrogen-atoms uninvolved in hydrogen bonds in a metal-organic framework.

Organic and hybrid materials are emerging classes of materials with interesting properties inclusive of ferroelectric and magnetic ordering. They also offer the possibility of proton disorder that is of fundamental importance and useful for applications. In materials that exhibit proton disorder, such disordered-protons usually participate in the hydrogen bonds. Unlike the cations that host the disordered-sites, it is discovered in metal guanidinium formates (C(NH2)3M2+(HCOO)3) that the proton disorder is in the anionic framework. This study based on single-crystal neutron diffraction uncovers the presence of disorder in the formato-hydrogens of metal guanidinium formates regardless of their symmetry. The target materials exhibit various types of potential energy surfaces. Here the proton disorder for the first time is identified in the hydrogen atoms that neither participate in the hydrogen bonds nor in physisorption. A future challenge is to understand the influence of this phenomenon on the physicochemical properties of various classes of materials.

Enhancement of the guest orderliness in a low-symmetric perovskite-type metal-organic framework influenced by Jahn-Teller distortion.

Copper guanidinium formate (CuGF) is an ABX3-type metal-organic framework bearing a polar space group, housing a guest-host connectivity between the guanidinium and formate ions. With the maiden data-set based on single-crystal neutron diffraction, we report the discovery of the guest orderliness which surprisingly accommodates an enhancement for low-symmetric CuGF, while the scenario is contrasting for the high-symmetric Mn cousin. We provide an in-depth evaluation of the inter-guanidinium scheme and thus propose the mechanism behind this unusual effect.

Correction: Neutron diffraction studies on the thermal expansion and anomalous mechanics in the perovskite-type [C(ND2)3]Me2+(DCOO)3 [Me = Cu, Mn, Co].

Correction for 'Neutron diffraction studies on the thermal expansion and anomalous mechanics in the perovskite-type [C(ND2)3]Me2+(DCOO)3 [Me = Cu, Mn, Co]' by M. Viswanathan et al., Phys. Chem. Chem. Phys., 2018, DOI: 10.1039/c8cp01245h.

Neutron diffraction studies on the thermal expansion and anomalous mechanics in the perovskite-type [C(ND2)3]Me2+(DCOO)3 [Me = Cu, Mn, Co].

The thermomechanical characteristics of [C(ND2)3]Me2+(DCOO)3 [Me = Cu, Co, Mn] have been evaluated by single-crystal and powder neutron diffraction. [C(ND2)3]Cu2+(DCOO)3, presenting with the polar space group Pna21, exhibits lattice expansion along the a and c axes, while the b-axis shows a crossover from negative to positive thermal expansion. The relative change in lattice parameters is independent in all directions, resulting in anisotropic thermal characteristics. The thermomechanical response is a collective effect of hingeing and deformation, with the former as the dominant factor. In this study, every individual hinge and strut are evaluated, unlike the conventional averaging of the mechanical units. The Mn cousin displays a higher magnitude of octahedral tilting than the Co-twin. Such an effect has direct consequences on higher expansivity for manganese guanidinium formate along all directions. Hingeing is the dominant factor in both Mn and Co-twins, with their relative values much closer than reported earlier.

Molecular and Statistical Analysis of Campylobacter spp. and Antimicrobial-Resistant Campylobacter Carriage in Wildlife and Livestock from Ontario Farms.

The objectives of this study were to (i) compare the carriage of Campylobacter and antimicrobial-resistant Campylobacter among livestock and mammalian wildlife on Ontario farms, and (ii) investigate the potential sharing of Campylobacter subtypes between livestock and wildlife. Using data collected from a cross-sectional study of 25 farms in 2010, we assessed associations, using mixed logistic regression models, between Campylobacter and antimicrobial-resistant Campylobacter carriage and the following explanatory variables: animal species (beef, dairy, swine, raccoon, other), farm type (swine, beef, dairy), type of sample (livestock or wildlife) and Campylobacter species (jejuni, coli, other). Models included a random effect to account for clustering by farm where samples were collected. Samples were subtyped using a Campylobacter-specific 40 gene comparative fingerprinting assay. A total of 92 livestock and 107 wildlife faecal samples were collected, and 72% and 27% tested positive for Campylobacter, respectively. Pooled faecal samples from livestock were significantly more likely to test positive for Campylobacter than wildlife samples. Relative to dairy cattle, pig samples were at significantly increased odds of testing positive for Campylobacter. The odds of isolating Campylobacter jejuni from beef cattle samples were significantly greater compared to dairy cattle and raccoon samples. Fifty unique subtypes of Campylobacter were identified, and only one subtype was found in both wildlife and livestock samples. Livestock Campylobacter isolates were significantly more likely to exhibit antimicrobial resistance (AMR) compared to wildlife Campylobacter isolates. Campylobacter jejuni was more likely to exhibit AMR when compared to C. coli. However, C. jejuni isolates were only resistant to tetracycline, and C.  coli isolates exhibited multidrug resistance patterns. Based on differences in prevalence of Campylobacter spp. and resistant Campylobacter between livestock and wildlife samples, and the lack of similarity in molecular subtypes and AMR patterns, we concluded that the sharing of Campylobacter species between livestock and mammalian wildlife was uncommon.

Cluster Analysis of Campylobacter jejuni Genotypes Isolated from Small and Medium-Sized Mammalian Wildlife and Bovine Livestock from Ontario Farms.

Using data collected from a cross-sectional study of 25 farms (eight beef, eight swine and nine dairy) in 2010, we assessed clustering of molecular subtypes of C. jejuni based on a Campylobacter-specific 40 gene comparative genomic fingerprinting assay (CGF40) subtypes, using unweighted pair-group method with arithmetic mean (UPGMA) analysis, and multiple correspondence analysis. Exact logistic regression was used to determine which genes differentiate wildlife and livestock subtypes in our study population. A total of 33 bovine livestock (17 beef and 16 dairy), 26 wildlife (20 raccoon (Procyon lotor), five skunk (Mephitis mephitis) and one mouse (Peromyscus spp.) C. jejuni isolates were subtyped using CGF40. Dendrogram analysis, based on UPGMA, showed distinct branches separating bovine livestock and mammalian wildlife isolates. Furthermore, two-dimensional multiple correspondence analysis was highly concordant with dendrogram analysis showing clear differentiation between livestock and wildlife CGF40 subtypes. Based on multilevel logistic regression models with a random intercept for farm of origin, we found that isolates in general, and raccoons more specifically, were significantly more likely to be part of the wildlife branch. Exact logistic regression conducted gene by gene revealed 15 genes that were predictive of whether an isolate was of wildlife or bovine livestock isolate origin. Both multiple correspondence analysis and exact logistic regression revealed that in most cases, the presence of a particular gene (13 of 15) was associated with an isolate being of livestock rather than wildlife origin. In conclusion, the evidence gained from dendrogram analysis, multiple correspondence analysis and exact logistic regression indicates that mammalian wildlife carry CGF40 subtypes of C. jejuni distinct from those carried by bovine livestock. Future studies focused on source attribution of C. jejuni in human infections will help determine whether wildlife transmit Campylobacter jejuni directly to humans.

Overview of best practices in conducting comparative-effectiveness reviews.

Comparative-effectiveness research (CER) reviews translate mountains of evidence into manageable and meaningful messages to inform clinical practice. CER reviews also have the potential to shorten the pipeline between research and practice. Reaching these goals through CER reviews requires adherence to CER principles and procedures, as well as the use of appropriate quantitative methods, qualitative methods, and clinical judgment. Comprehensiveness, objectivity, transparency, scientific rigor, relevance, and responsiveness are the principles that underpin best practices in conducting a CER review.

Influence of lattice distortion on the Curie temperature and spin-phonon coupling in LaMn0.5Co0.5O3.

Two distinct ferromagnetic phases of LaMn(0.5)Co(0.5)O(3) having monoclinic structure with distinct physical properties have been studied. The ferromagnetic ordering temperature T(c) is found to be different for both the phases. The origin of such contrasting characteristics is assigned to the changes in the distance(s) and angle(s) between Mn-O-Co resulting from distortions observed from neutron diffraction studies. Investigations on the temperature dependent Raman spectroscopy provide evidence for such structural characteristics, which affects the exchange interaction. The difference in B-site ordering which is evident from the neutron diffraction is also responsible for the difference in T(c). Raman scattering suggests the presence of spin-phonon coupling for both the phases around the T(c). Electrical transport properties of both the phases have been investigated based on the lattice distortion.

Methylation of E-cadherin and hMLH1 genes in Indian sporadic breast carcinomas.

Hypermethylation of promoter regions leading to inactivation of tumor suppressor genes is a common event in the progression of several tumor types. We have employed a novel restriction digestion based multiplex PCR assay to analyse the methylation status of promoter regions of tumor suppressor genes (p16, hMLH1, MGMT and E-cadherin) in sporadic breast carcinomas of Indian women. The present results indicated the absence of hypermethylation in promoter region of p16 and MGMT genes. However, 6 of the 19 (31.6%) sporadic breast carcinomas showed hypermethylation in the promoters of two of the genes analysed; three in hMLH1 and another three in E-cad. Since our earlier studies have shown lack of genetic alterations such as missense mutations and deletions in the tumor associated genes-p16, ras and p14ARF in sporadic breast tumors, the epigenetic alterations of the two genes reported in the present study could be of interest and might be among the events in the genesis/progression of sporadic breast carcinomas.