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Late-onset hypogonadism (LOH) is generally treated with testosterone replacement therapy. Intramuscular injection of testosterone enanthate is used for LOH in Japan but requires regular painful injections administered every 2-3 weeks at a clinic. Testosterone 2% (AndroForte 2

The power that develops when communities define their urban planning agendas is now becoming more and more evident, and community-led development may offer long-lasting upgrades to metropolitan areas. A city's social and physical environment can either enable or hinder its residents' well-being and ability to become independent whereas there are still wide gaps between understanding the inclusive urban environment and a healthy environment. There remains an overwhelming reality of alienation of the users from their environment. The term inclusive cities are widely used to refer to the inclusion of marginalized communities – slum dwellers, migrants, minority groups, women or young people – in urban processes. This paper aimed at defining an inclusive and healthy urban environment in the global south, its benefits, and its characteristics to redefine the community. An empirical article review was conducted to establish the concepts. Findings from the reviews show different indicators of urban environment exclusion and drivers of inclusivity concepts. It is therefore concluded that for urban sustainability, each community should be given priority for an inclusive healthy urban environment. Stakeholders of the global south should therefore provide policies and implement programs for total inclusiveness.

To clarify the efficacy of low-intensity extracorporeal shockwave therapy for patients with erectile dysfunction, compare the efficacy between two types of lithotripters (ED1000 [focused type] and Renova [linear type]), and detect factors indicative of therapeutic gain with the treatment.This retrospective study included 76 patients (52.8 ± 11.7 years) treated by ED1000 (12 times over 9 weeks) and 484 patients (52.5 ± 11.6 years) treated by Renova (4 times over 4 weeks). Age, sexual symptoms scores, and blood examinations were assessed. Efficacy was judged by improvement of the scores and patient satisfaction and compared between patients at 1 month after treatment with the lithotripters. Independent factors influencing efficacy by Renova were also assessed.Sexual symptom scores were improved significantly by both lithotripters, although the changes in the scores did not differ significantly between them. Efficacy rate as judged by patient satisfaction was 65.8% with the ED1000 and 71.1% with Renova, also without significant difference. Among several factors including age, sexual symptoms scores, endocrinological factors, metabolic factors, and the rate of phosphodiesterase type 5 inhibitor use, only age was found to be an independent factor influencing the efficacy of Renova.We clearly showed the high efficacy of both lithotripters. Although the efficacy rate did not differ between them, we speculated that the fewer treatment sessions needed with the Renova versus the ED1000 would be a great advantage for patients. We also suggest that Renova should be recommended for patients younger than 70 years of age.

Introduction Desmoplastic malignant pleural mesothelioma (DMPM) is a sarcoma type mesothelioma, comprising about 5% of malignant pleural mesotheliomas. Although effusion cytology is commonly used as the primary diagnostic approach for mesothelioma, this may not be useful for DMPM due to its desmoplastic nature and bland cellular atypia. We hereby report a case of DMPM diagnosed through autopsy along with its cytological features that have not been described previously. Case presentation A male in his 60s with a history of occupational asbestos exposure was referred to our hospital with right chest pain. Chest computed tomography scan showed right pleural effusion. Thirteen months later, the patient died of respiratory failure. In autopsy, the scrape-imprint smear and the pleural effusions cytology were performed. The scrape-imprint smear samples exhibited spindle cells with mild nuclear atypia and grooves with fibrous stroma. In the pleural effusion cytology, spindle cells having mild nuclear atypia and grooves with loose epithelial connections were observed. Histological examination of the right pleura showed spindle cells proliferating with dense collagen fibers, as seen in cytological samples, thus rendering the diagnosis of DMPM. Diagnosis was confirmed by fluorescence in situ hybridization. Conclusion Cytological procedures, such as pleural effusion cytology and scrape-imprinting method, may be useful as an ancillary tool in the diagnosis of rare tumors such as DMPM.

Aims: This work aimed to evaluate the antimicrobial potential of the stem bark extracts of P. biglobosa on selected bacteria species, Escherichia coli, and Staphylococcus aureus. Place and Duration of Study: Microbiology laboratory, Department of Biological Sciences, Bingham University-Karu, Nasarawa State, Nigeria. Methodology: Plant extracts were made by boiling, soaking and methanol extraction, and the antimicrobial assay was performed using the disc and agar-well diffusion methods. Results: The results indicated all the extract exhibited antimicrobial properties. The highest potential activity was observed with the macerated extract with zones of inhibition at 12.5 mm and 6.5 mm against S. aureus and E. coli, respectively in the agar-well diffusion method while no active zone of inhibition was recorded in the disk diffusion method. It was noted that the macerated extract showed the highest MIC of 100 mg/ml with a zone of inhibition at 15.0 mm against S. aureus. Conclusion: The results obtained showed that the macerated extract of the plant possess the highest antimicrobial effect against S. aureus, and E. coli. Although observed potency of this extract in vitro, may not be translated to the same activity in vivo. However, the results confirmed the efficacy of the plant as a natural antimicrobial and can be further investigated for possible antimicrobial drug discovery.

Background: Male involvement in family planning (FP) is most often associated with better health outcomes for the family. This study assessed male involvement in FP at Fadan Kamantan, a rural community in Zango Kataf Local Government Area of Kaduna State, North Western Nigeria. Methods: This was a community-based descriptive cross-sectional study conducted among 166 married men selected using multi-staged sampling technique. A set of structured, interviewer-administered questionnaires were used to obtain information from the respondents. Data was analyzed with IBM SPSS version 23.0 and STATA/SE 12. The level of statistical significance was set at p

Kawasaki disease (KD) is a systemic vasculitis syndrome that mostly affects children under 4 years old. Among the reported KD cases, only 1% were over 10 years old. We herein report 2 cases of adult-onset KD (AKD) in 19- and 17-year-old boys diagnosed with a persistent fever and cervical lymphadenitis. Both patients showed cardiac complications, such as coronary artery dilation and myocarditis. Repeated intravenous immunoglobulin therapy was effective in the 19-year-old, while plasma exchange therapy was needed for the 17-year-old, with no sequelae noted at discharge. KD should be considered as a differential diagnosis for persistent fever in adults.

Malaria is a life-threatening disease transmitted through the bite of an infected female Anopheles mosquito. Human behaviour contributes significantly to malaria transmission. The study aimed to investigate malaria infection in relation to the knowledge, attitudes, and perception of participants in Shongom LGA. Gombe State. Consent was sought from the participants, 377 people were enrolled, blood samples were collected, and a thick blood smear was performed to check the presence of malaria parasites. Information of the participants i.e., gender, age, employment and marital status, knowledge, attitudes, and perception of malaria was obtained through the administration of questionnaires, SPSS version 26.0 was used for the data analysis. Of the 377 participants tested for malaria, 144(38.2%) were positive. Assessment of knowledge of participants with regards to malaria revealed, that 112(29.7%) opined that malaria is transmitted through a mosquito bite, fever 66(17.5%) is the major sign/symptom of malaria, 50(13.3%) used LLIN for malaria protection p>0.05 which is statistically insignificant. Investigation of the attitudes of the participants in relation to malaria showed that 123(32.6%) infected with malaria stayed outdoors at night, the major reason for staying outdoors at night was to get fresh air 45(36.6%) p0.05 which is statistically insignificant. With regards to the perception of malaria, 71(18.8%) said malaria is common during the rainy season, and 77(20.0%) opted that males are more susceptible to malaria, and mostly affects adults as revealed by 66(15.9%), however, 90(23.9%) said malaria is curable and 98(26.0%) said malaria is a common illness in the communities p>0.05 which is statistically insignificant. 134(35.5%) said that malaria can cause death p0.05 which is statistically insignificant. Concern authorities should strategies and prioritize behavioural change to reduce malaria transmission.

Background Adenoid cystic carcinoma of the trachea (ACCT) is a rare cancer; ACCT with thyroid invasion is particularly rare. We first suspected anaplastic thyroid carcinoma (ATC) but diagnosed ACC after performing fine needle aspiration cytology (FNAC). A tracheal origin was confirmed after operation. Case description We report the case of a 77-year-old female presenting to our hospital with acute inspiratory dyspnea requiring emergency tracheotomy. Physical examination revealed a right anterior neck swelling with a hard and unmovable mass. Computed tomography (CT) and ultrasonography (US) showed tumor extension to the right thyroid lobe, and between the first and third tracheal rings, which caused severe stenosis of the lumen. Next, we performed FNAC. Clinical findings were highly suspicious for ACCT with thyroid invasion. Thirty-five days after the first visit to our department, the patient underwent total laryngectomy, cervical esophagectomy, and thyroidectomy with bilateral selective neck dissections at another hospital. The tumor was located in the right posterior wall of the trachea, with extension into the right thyroid gland. Pathological examination showed an infiltrative carcinomatous proliferation with tubular and cribriform patterns. The tumor was classified as pT4N1. A definite diagnosis was made after histopathological analyis of the surgical specimen confirmed ACCT. The tumor was found to be positive for FABP7, a putative prognostic marker of ACC, and metastasized to the lungs 3 years after the surgery. Conclusions ACCT with thyroid invasion is an extremely rare malignant neoplasm. FNAC was useful for differentiating ACCT from other diagnoses and enabled appropriate surgical treatment.

Increased central venous pressure in congestive heart failure is responsible for renal dysfunction, which is mediated by renal venous congestion. Pericyte detachment from capillaries after renal congestion might trigger renal fibrogenesis via pericyte-myofibroblast transition (PMT). Platelet-derived growth factor receptors (PDGFRs), which are PMT indicators, were upregulated in our recently established renal congestion model. This study was designed to determine whether inhibition of the PDGFR pathway could suppress tubulointerstitial injury after renal congestion.The inferior vena cava between the renal veins was ligated in male Sprague-Dawley rats, inducing congestion only in the left kidney. Imatinib mesylate or vehicle were injected intraperitoneally daily from 1 day before the operation. Three days after the surgery, the effect of imatinib was assessed by physiological, morphological and molecular methods. The inhibition of PDGFRs against transforming growth factor-β1 (TGFB1)-induced fibrosis was also tested in human pericyte cell culture.Increased kidney weight and renal fibrosis were observed in the congested kidneys. Upstream inferior vena cava (IVC) pressure immediately increased to around 20 mmHg after IVC ligation in both the imatinib and saline groups. Although vasa recta dilatation and pericyte detachment under renal congestion were maintained, imatinib ameliorated the increased kidney weight and suppressed renal fibrosis around the vasa recta. TGFB1-induced elevation of fibrosis markers in human pericytes was suppressed by PDGFR inhibitors at the transcriptional level.The activation of the PDGFR pathway after renal congestion was responsible for renal congestion-induced fibrosis. This mechanism could be a candidate therapeutic target for renoprotection against renal congestion-induced tubulointerstitial injury.

Previous studies have reported the relationship between housing environment and health, although due to cost and effort, it was difficult to conduct housing condition surveys on a large scale. The CASBEE Housing Health Checklist (the Checklist) made it possible to easily evaluate the housing condition from the resident's perspective. This study examined the relationship between housing coldness/warmth evaluation using the Checklist and psychological distress in a large-scale general Japanese population.A cross-sectional study.We analysed data from 29,380 people aged ≥20 years who lived in Miyagi Prefecture, Japan. As an assessment of housing coldness/warmth, we used the Checklist. We classified participants' total scores on the Checklist related to coldness/warmth into quartiles. The Kessler 6 scale was used as an indicator of psychological distress. Multivariable logistic regression models were used to estimate the adjusted odds ratio (OR) and 95% confidence intervals (CIs). Adjusted OR and P-values for linear trends were calculated using the quartiles of the Checklists' score.Among participants in Q1 (i.e., poorer subjective house condition), the percentage of people with psychological distress was high. Compared to the highest quartile, Q1 showed poorer evaluation of housing coldness/warmth, and higher OR for psychological distress. The OR (95% CI) of psychological distress for Q3, Q2, and Q1 compared with Q4 were 1.93 (1.74-2.14), 2.82 (2.55-3.12), and 5.78 (5.25-6.35), respectively.Housing coldness/warmth evaluation was significantly related to psychological distress. This finding suggests that maintaining a comfortable thermal environment at home could be important for residents' mental health.

BackgroundChronic kidney disease (CKD) impacts prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). While estimated glomerular filtration rate (eGFR) calculated from serum creatinine [eGFR (creatinine)] is affected by body muscle mass which reflects frailty, eGFR calculated from serum cystatin C [eGFR (cystatin C)] is independent of body composition, resulting in better renal function assessment.MethodsThis study included 390 consecutive patients with symptomatic severe aortic stenosis (AS) who underwent TAVI, and measured cystatin C-based eGFR at discharge. Patients were divided into two groups, with or without CKD estimated with eGFR (cystatin C). The primary endpoint of this study was the 3-year all-cause mortality after TAVI.ResultsThe median patient age was 84 years, and 32.8% patients were men. Multivariate Cox regression analysis indicated that eGFR (cystatin C), diabetes mellitus, and liver disease were independently associated with 3-year all-cause mortality. In the receiver-operating characteristic (ROC) curve, the predictive value of eGFR (cystatin C) was significantly higher than that of eGFR (creatinine). Furthermore, Kaplan–Meier estimates revealed that 3-year all-cause mortality was higher in the CKD (cystatin C) group than that in the non-CKD (cystatin C) group with log-rank p = 0.009. In contrast, there was no significant difference between the CKD (creatinine) and non-CKD (creatinine) groups with log-rank p = 0.94.ConclusionseGFR (cystatin C) was associated with 3-year all-cause mortality in patients who underwent TAVI, and it was superior to eGFR (creatinine) as a prognostic biomarker.

Background We investigated the effect of the number of laser shots applied on the myopic variables to elucidate the mechanism of myopia development in laser-treated retinopathy of prematurity (ROP) eyes. Methods A total of 33 eyes of 17 infants with ROP who underwent laser treatment were included in the analysis. Cycloplegic retinoscopic refraction testing was carried out and the spherical equivalent (SE) was calculated. Relationships between SE and various variables (including the number of laser shots applied) were examined. In addition, an age-matched control group without ROP was prepared and ocular structural parameters were compared. Results Although there was no statistical difference in axial length (AL) between two groups (p = 0.88), SE was significantly more myopic in the ROP group (p Conclusions In laser-treated ROP eyes, AL, CR, and CLP were related to the degree of myopia. Moreover, the number of shots applied also affected the myopic status in laser-treated ROP eyes. Among AL, CR, and CLP, only CLP was correlated with the laser shots applied.

Pancreatic cancer remains a disease with unmet clinical needs and inadequate diagnostic, prognostic, and predictive biomarkers. In-depth characterization of the disease proteome is limited. This study thus aims to define and describe protein networks underlying pancreatic cancer and identify protein centric subtypes with clinical relevance. Mass spectrometry–based proteomics was used to identify and quantify the proteome in tumor tissue, tumor-adjacent tissue, and patient-derived xenografts (PDX)-derived cell lines from patients with pancreatic cancer, and tissues from patients with chronic pancreatitis. We identified, quantified, and characterized 11,634 proteins from 72 pancreatic tissue samples. Network focused analysis of the proteomics data led to identification of a tumor epithelium–specific module and an extracellular matrix (ECM)-associated module that discriminated pancreatic tumor tissue from both tumor adjacent tissue and pancreatitis tissue. On the basis of the ECM module, we defined an ECM-high and an ECM-low subgroup, where the ECM-high subgroup was associated with poor prognosis (median survival months: 15.3 vs. 22.9 months; log-rank test, P = 0.02). The ECM-high tumors were characterized by elevated epithelial–mesenchymal transition and glycolytic activities, and low oxidative phosphorylation, E2F, and DNA repair pathway activities. This study offers novel insights into the protein network underlying pancreatic cancer opening up for proteome precision medicine development.Significance:Pancreatic cancer lacks reliable biomarkers for prognostication and treatment of patients. We analyzed the proteome of pancreatic tumors, nonmalignant tissues of the pancreas and PDX-derived cell lines, and identified proteins that discriminate between patients with good and poor survival. The proteomics data also unraveled potential novel drug targets.

Supplementary figures

Univariate cox regression analysis (left) including clinical, pathological, and molecular variables. Multivariate cox regression analysis (right) including the variables with significant or trending association with patient survival in the univariate analysis.

Histological composition of the samples along with assigned transcriptomics and proteomics classifications for PDAC

Proteins members of modules M1-M5

Top 25% most variable proteins used in WGCNA

Differential expression analysis of M2 and M4 proteins between PDAC and tumor adjacent tissue samples (Wilcoxon-rank sum test)

Supplementary method describing HiRIEF-nanoLC-MS_MS based proteomics technology

Patients and samples overview

Proteins (and the assigned module) identified in our dataset overlapping with the proteins with significantly higher abundance in PDAC tumor tissue compared to adjacent tissue/normal ducts in the study of Cao et al.2021

Enriched pathways in Module M1-M5

Table shows the pathway deregulated in OUH and TCGA cohort.

Despite advances in diagnostics, less than 5% of patients with periampullary tumors experience an overall survival of five years or more. Periampullary tumors are neoplasms that arise in the vicinity of the ampulla of Vater, an enlargement of liver and pancreas ducts where they join and enter the small intestine. In this study, we analyzed copy number aberrations using Affymetrix SNP 6.0 arrays in 60 periampullary adenocarcinomas from Oslo University Hospital to identify genome-wide copy number aberrations, putative driver genes, deregulated pathways, and potential prognostic markers. Results were validated in a separate cohort derived from The Cancer Genome Atlas Consortium (n = 127). In contrast to many other solid tumors, periampullary adenocarcinomas exhibited more frequent genomic deletions than gains. Genes in the frequently codeleted region 17p13 and 18q21/22 were associated with cell cycle, apoptosis, and p53 and Wnt signaling. By integrating genomics and transcriptomics data from the same patients, we identified CCNE1 and ERBB2 as candidate driver genes. Morphologic subtypes of periampullary adenocarcinomas (i.e., pancreatobiliary or intestinal) harbor many common genomic aberrations. However, gain of 13q and 3q, and deletions of 5q were found specific to the intestinal subtype. Our study also implicated the use of the PAM50 classifier in identifying a subgroup of patients with a high proliferation rate, which had impaired survival. Furthermore, gain of 18p11 (18p11.21-23, 18p11.31-32) and 19q13 (19q13.2, 19q13.31-32) and subsequent overexpression of the genes in these loci were associated with impaired survival. Our work identifies potential prognostic markers for periampullary tumors, the genetic characterization of which has lagged. Cancer Res; 76(17); 5092–102. ©2016 AACR.

Supplementary Data from DNMT3B Expression Might Contribute to CpG Island Methylator Phenotype in Colorectal Cancer

The table shows the genes, chromosomal location and frequency of deletion and amplification of genes in OUH (PAs (n=54), cell lines (n=3) and IPMN (n=3) and TCGA data sets (n=127).

Purpose: DNA methyltransferase-3B (DNMT3B) plays an important role in de novo CpG island methylation. Dnmt3b can induce colon tumor in mice with methylation in specific CpG islands. We hypothesized that cellular DNMT3B level might influence the occurrence of widespread CpG island methylation (i.e., the CpG island methylator phenotype, CIMP) in colon cancer.Experimental Design: Utilizing 765 colorectal cancers in two cohort studies, we detected DNMT3B expression in 116 (15%) tumors by immunohistochemistry. We assessed microsatellite instability, quantified DNA methylation in repetitive long interspersed nucleotide element-1 (LINE-1) by Pyrosequencing, eight CIMP-specific promoters [CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1], and eight other CpG islands (CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14, and WRN) by real-time PCR (MethyLight).Results: Tumoral DNMT3B overexpression was significantly associated with CIMP-high [≥6/8 methylated CIMP-specific promoters; odds ratio (OR), 3.34; 95% confidence interval, 2.11-5.29; P < 0.0001]. The relations between DNMT3B and methylation in 16 individual CpG islands varied substantially (OR, 0.80-2.96), suggesting variable locus-to-locus specificities of DNMT3B activity. DNMT3B expression was not significantly related with LINE-1 hypomethylation. In multivariate logistic regression, the significant relation between DNMT3B and CIMP-high persisted (OR, 2.39; 95% confidence interval, 1.11-5.14; P = 0.026) after adjusting for clinical and other molecular features, including p53, β-catenin, LINE-1, microsatellite instability, KRAS, PIK3CA, and BRAF. DNMT3B expression was unrelated with patient outcome, survival, or prognosis.Conclusions: Tumoral DNMT3B overexpression is associated with CIMP-high in colorectal cancer. Our data support a possible role of DNMT3B in nonrandom de novo CpG island methylation leading to colorectal cancer.

This file contains the legends of supplementary figures and tables.

1a) Amplification and deletion of cytobands in OUH cohort. 1b) Amplification and deletion of cytobands in TCGA cohort. The rows represent the cytobands while the columns represent the samples. The color bars on y-axis represent the chromosomes. The red color in the heatmap represents the amplification, green color represent the deletion while black represent the normal state.

The minor allele frequency is in blue and purple is the total copy number.

Table shows the correlation score (r) between allele frequency and gene expression in OUH and TCGA cohort

The minor allele frequency is in blue and purple is the total copy number.

Purpose: Cyclin D1 and cyclin-dependent kinases (CDK) are commonly activated in colorectal cancer. The activity of cyclin D1 can be blocked by CDK inhibitors, including p27 (CDKN1B) and p21 (CDKN1A, which is induced by p53). However, prognostic significance of tumoral cyclin D1 remains uncertain, and no previous study has considered potential confounding effect of p53, p21, p27, and related molecular events [microsatellite instability (MSI), CpG island methylator phenotype, and LINE-1 hypomethylation].Experimental Design: Among 602 colon cancer patients (stage I-IV) in two prospective cohort studies, cyclin D1 overexpression was detected in 330 (55%) tumors by immunohistochemistry. Cox proportional hazard models computed hazard ratios (HR) of colon cancer–specific and overall mortalities, adjusted for patient characteristics and tumoral molecular features, including p53, p21, p27, cyclooxygenase-2, fatty acid synthase, LINE-1 methylation, CpG island methylator phenotype, MSI, BMI, KRAS, and BRAF.Results: Cyclin D1 overexpression was associated with a low cancer-specific mortality in Kaplan-Meier analysis (P = 0.006), and in both univariate Cox regression [unadjusted HR, 0.64; 95% confidence interval (CI), 0.47-0.88; P = 0.0063] and multivariate analyses (adjusted HR, 0.57; 95% CI, 0.39-0.84; P = 0.0048). Similar findings were observed for an overall mortality (adjusted HR, 0.74; 95% CI, 0.57-0.98; P = 0.036). Notably, the effect of cyclin D1 on survival might differ by MSI status (Pinteraction = 0.008). Compared with tumors that were both cyclin D1–negative and MSI-low/microsatellite stable, the presence of either cyclin D1 or MSI-high or both seemed to confer better clinical outcome (adjusted HR point estimates, 0.10-0.65).Conclusions: Cyclin D1 overexpression is associated with longer survival in colon cancer.

The x-axis represents the genomic position and is divided into 22 facets for 22 chromosomes. The y-axis represents the frequency of chromosomal gain and losses for five subtypes based on site of origin. The number of samples in each subtypes are PDAC: 28, bile duct: 4, ampulla P: 6, ampulla I: 7, duodenum: 9.

Supplementary Data from A Cohort Study of Cyclin D1 Expression and Prognosis in 602 Colon Cancer Cases

4A) Scatter plot shows the correlation between GII and ploidy of the tumors in OUH cohort. 4B) Scatter plot shows the correlation between GII and ploidy of the tumors in TCGA cohort. The x-axis represent the genome instability index while the y-axis represent the ploidy of the tumors

The COVID’19 pandemic, recent spike of Omicron variant and the upsurge in air pollution in metropolitan cities like Delhi has highlighted the importance of oxygen cylinders andother equipment’s. The various units in the health system such as: General wards, Emergency transport, Delivery rooms, Operatingtheaters, Intensive care units (ICU) also require a regular supply of oxygen. Thus, timely and powerful planning for reliable oxygensupply and delivery is needed to protect and save lives of people who are in need. Due to the unavailability of a proper channel of acquiring Oxygen during the pandemic, forced people to search for the supply of oxygen through phone calls and various social media platforms. But only few people got reliable suppliers and many could not get their demand satisfied at the right time. Evenhospitals faced the same situation. To combat such problems,in this project we propose a unique system for Oxygen Supply Management to people and hospitals which can meet the crisisin an effective way. In order to overcome the shortage of oxygen in the coming times, this proposed system will be launched as a digital platform to fast-pace the supply chain to both people and hospitals. Index Terms: Covid-19, pandemic, Omicron

BackgroundDNA replisome is a molecular complex that plays indispensable roles in normal DNA replication. IMAGE-I syndrome is a DNA replisome-associated genetic disease caused by biallelic mutations in the gene encoding DNA polymerase epsilon catalytic subunit 1 (POLE). However, the underlying molecular mechanisms remain largely unresolved.MethodsThe clinical manifestations in two patients with IMAGE-I syndrome were characterised. Whole-exome sequencing was performed and altered mRNA splicing and protein levels of POLE were determined. Subcellular localisation, cell cycle analysis and DNA replication stress were assessed using fibroblasts and peripheral blood from the patients and transfected cell lines to determine the functional significance ofPOLEmutations.ResultsBoth patients presented with growth retardation, adrenal insufficiency, immunodeficiency and complicated diffuse large B-cell lymphoma. We identified three novelPOLEmutations: namely, a deep intronic mutation, c.1226+234G>A, common in both patients, and missense (c.2593T>G) and in-frame deletion (c.711_713del) mutations in each patient. The unique deep intronic mutation produced aberrantly spliced mRNAs. All mutants showed significantly reduced, but not null, protein levels. Notably, the mutants showed severely diminished nuclear localisation, which was rescued by proteasome inhibitor treatment. Functional analysis revealed impairment of cell cycle progression and increase in the expression of phospho-H2A histone family member X in both patients.ConclusionThese findings provide new insights regarding the mechanism via whichPOLEmutants are highly susceptible to proteasome-dependent degradation in the nucleus, resulting in impaired DNA replication and cell cycle progression, a characteristic of DNA replisome-associated diseases.

BACKGROUND Alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) are enzymes associated with diabetes mellitus (DM) prevalence. However, limited information is available regarding the association of liver enzymes and DM consistently present in obese and non-obese individuals. We examined whether the combination of ALT and GGT enzymes is associated with the prevalence of DM regardless of obesity in a general Japanese population. METHODS We conducted a cross-sectional study of 62,786 participants aged ≥20 years who lived in Miyagi and Iwate, Japan. We divided all the participants into eight groups according to the ALT level (low

A 51-year-old woman was admitted because of hypercalcemia. Neck ultrasonography and computed tomography revealed the presence of parathyroid cysts on both sides. After primary hyperparathyroidism was diagnosed by technetium-99m-methoxyisobutylisonitrile scintigraphy, the patient was successfully treated with total parathyroidectomy and autotransplantation. She also had a non-functioning pancreatic neuroendocrine tumor, prolactinoma, and adrenal tumors with subclinical Cushing's syndrome. Given these clinical features and her family history, multiple endocrine neoplasia type 1 (MEN1) was suspected, and germline DNA sequencing revealed a missense mutation (c.1013TC, [corrected] p.Leu338Pro) in exon 7 of MEN1. This case demonstrates the phenotypic and genetic diversity of MEN1.

The utilization of composite flour from wheat and crayfish in the production of cookies was investigated. The wheat and crayfish flour were blended at the ratios of 100:0, 97.5:2.5, 95:5, 92.5:7.5, and 90:10, respectively. The cookies were evaluated for their proximate, minerals, physical and Sensory properties; The results of the proximate analysis showed an increase in the protein content (7.88-38.94%), moisture (4.61-6.27%), fiber (1.95-3.65%) and fat (0.98-3.11%) as the level of crayfish flour increased while there was a decrease in the carbohydrate content (77.94-40.45%) as the level of crayfish flour increased. The ash content ranged from 5.77 to 7.89%. The mineral compositions showed an increased trend in calcium, potassium, and sodium contents of the cookies as the crayfish supplementation increased but decreased phosphorus content as the level of crayfish supplementation increased. Iron ranged from 4.70-to 5.20. The calcium, potassium, iron, sodium and phosphorus ranged from 5.35-6.60 mg/100g, 650-930 mg/100g, 4.75-5.20 mg/100g, 670-870 mg/100g and 1577-23420 mg/100g respectively. The cookies' weight, diameter, and thickness decreased as the level of crayfish supplementation increased. There was a significant (p

This research work highlight the production and nutritional quality of Nigeria base -Masa from broken rice enriched with African yam bean and cricket blends was investigated. Blends of different proportions of broken rice, African yam bean and cricket were prepared at 100 %, 80/0/20 %, 80/20/0 % and 80/10/10 % respectively. The proximate, vitamins and minerals, antinutrients contents and sensory evaluation of the Masa products were determined. The data obtained showed that moisture, protein, fat, ash carbohydrates and energy contents ranged from 38.46-44.48 %, 5.60-15.32 %, 0.71-9.71 %, 0.51-3.17 %, 0.61-0.79 %, 26.71-54.13 % and 245.25-270.77 kcal/100g respectively. The range values for vitamins and minerals are β-carotene (0.34-12.33 µg/100g), vitamin C (0.52-10.61 mg/100g), potassium (24.93-37.87 mg/100g), calcium (142.03-284.11 mg/100g), phosphorus (64.89-127.71 mg/100g), and iron (22.06-50.67 mg/100g). The antinutrients ranged from 0.095-1.860 mg/100g for alkaloids, 0.535-2.600 mg/100g for tannins, 0.040-1.550 mg/100g for phytates and 0.015-0.285 mg/100g for oxalates. The colour, aroma, taste, texture and general acceptability of the sensory attributes results ranged from 6.13-7.73, 6.60-7.07, 6.27-7.33, 5.93-6.73 and 6.67-7.73 respectively, however masa produced from sample 250 (100:0:0 % broken rice:African yam bean: cricket ) and 252 (80:20:0 Broken rice: African yam bean:cricket) substitution were generally accepted more than other Masa samples.

SUMMARY: This article applies the initiation model, developed by Jens Peter Schjødtas a tool to identify themes of initiation in Old Norse myths, to the prose introductionof the eddic poem Grímnismál. After having introduced Schjødt’s initiation model, thearticle contextualises the prose introduction within the themes of the myth found in thepoem; then, it applies the initiation model to the prose text’s figures of Geirrøðr andAgnarr; and, lastly, it focusses on the cunning role of Frigg in the prose. This leads tothe suggestion that the myth that frames Grímnismál may be a story aboutcontextualizing war and warrior ways in a society of peace, with initiation as an idealtool of 'civilizing' the ruling powers. RESUME: Denne artikel anvender initiationsmodellen, udviklet af Jens Peter Schjødtsom et værktøj til at identificere initiationstematikker i norrøne myter, påprosaintroduktionen af eddadigtet Grímnismál. Efter at have introduceret Schjødtsinitiationsmodel, kontekstualiserer artiklen prosaintroduktionen inden for de mytisketemaer, der findes i digtet, dernæst anvender den initiationsmodellen på prosatekstensfigurer Geirrøðr og Agnarr og slutteligt fokuserer den på Friggs listige rolle i teksten.Dette leder til forslaget, at myten, der omrammer Grímnismál, kan være en fortællingom at kontekstualisere krig og krigeres adfærd i et samfund bygget på fred medinitiation som et ideelt værktøj til at ‘civilisere’ de herskende magter.