Real-time genomic investigation underlying the public health response to a Shiga toxin-producing Escherichia coli O26:H11 outbreak in a nursery.

Shiga toxin-producing Escherichia coli (STEC) is a significant cause of gastrointestinal infection and the haemolytic-uremic syndrome (HUS). STEC outbreaks are commonly associated with food but animal contact is increasingly being implicated in its transmission. We report an outbreak of STEC affecting young infants at a nursery in a rural community (three HUS cases, one definite case, one probable case, three possible cases and five carriers, based on the combination of clinical, epidemiological and laboratory data) identified using culture-based and molecular techniques. The investigation identified repeated animal contact (animal farming and petting) as a likely source of STEC introduction followed by horizontal transmission. Whole genome sequencing (WGS) was used for real-time investigation of the incident and revealed a unique strain of STEC O26:H11 carrying stx2a and intimin. Following a public health intervention, no additional cases have occurred. This is the first STEC outbreak reported from Israel. WGS proved as a useful tool for rapid laboratory characterization and typing of the outbreak strain and informed the public health response at an early stage of this unusual outbreak.

Outcome of single-stage transanal endorectal pull through for short segment Hirschsprung's disease in neonates and infants.

Hirschsprung's disease (HD) is developmental disorder of the enteric nervous system. Diagnosis can be confirmed by rectal biopsy. The surgical management of HD includes so many procedures. The purpose of this study was to evaluate the out come of single-stage transanal endorectal pull-through operation for short segment HD in neonates and infants. This prospective study was carried out in the Department of Pediatric Surgery, Dhaka Shishu (Children) Hospital, Dhaka, Bangladesh during the period from January 2004 to December 2009. The study included neonates & infants (age 1 day to 1 year) of both sex, who were clinically suspected and biopsy proven HD with barium enema suggesting rectosigmoid HD. We excluded patients with short segment HD who had associated anomalies, and with hugely dilated proximal colon, operated cases with less than 6 months' follow up. During study period, single-stage transanal endorectal pull through (TEP) operation done in 68 neonates and infants patients (8 excluded) of short segment HD. The mean operative time, postoperative hospital stay, followed up time were 120 minutes, 7.94 days and 12 months respectively. Transeverse colostomy was needed in 4 patients because of anastomotic leakage and they were complicated with anastomotic stenosis, however managed by progressive dilatation. Overall parents' satisfaction was achieved. Single-stage primary transnanl endorectal pull-through for short segment HD is feasible in neonates and infants. It preserves all the advantages of minimally invasive surgery. TEP is a better option in terms of comfort, operative success, postoperative morbidity, cosmetic appearance and parents' satisfaction.

Association between Serum Total Cholesterol and Blood Pressure in Combined Oral Contraceptive Pill Users.

Oral contraceptives pills (OCPs) are one of the most commonly used methods of birth control by women worldwide. Presently, worldwide about 100 million women are current users of combined hormonal contraceptives (COC) most frequently used in the western world. The most frequently used agents are a combination of drugs containing both an estrogen and a progesteron. This combination is considered to be highly efficacious, generally considered 99.9% and a use effectiveness of 97.0% to 98.0%. This study was done to find out the association of serum total cholesterol and blood pressure in combined oral contraceptive pill users. This cross sectional study was carried out in the Department of Physiology, Mymensingh Medical College, Bangladesh between the periods from July 2021 to June 2022. A total number of 120 reproductive aged women, age ranged from 15-55 years were included in this study. They were divided into two group, sixty (60) combined oral contraceptive pill users were taken as study group (Group II) and sixty (60) age matched oral pill non users subjects were taken as control group (Group I). Data were expressed as mean±SD and statistical significance of difference among the group was calculated by unpaired students' 't' test and pearson's correlation coefficient test. Pearson 'r' value of systolic blood pressure and diastolic blood pressure are 0.582 and 0.416 respectively indicates positive correlation with serum total cholesterol. Correlation is statistically highly significant (p<0.001). Blood pressure and serum total cholesterol were positively connected in study group in comparison to control group respectively. So from this study, it can be concluded that there is a significant association between serum total cholesterol and blood pressure with oral contraceptives.

Analysis of two layered peristaltic-ciliary transport of Jeffrey fluid and in vitro preimplantation embryo development.

The analysis of peristaltic-ciliary transport in the human female fallopian tube, specifically in relation to the growing embryo, is a matter of considerable physiological importance. This paper proposes a biomechanical model that incorporates a finite permeable tube consisting of two layers, where the Jeffrey fluid model characterizes the viscoelastic properties of the growing embryo and continuously secreting fluid. Jeffrey fluid entering with some negative pressure gradient forms the core fluid layer while continuously secreting Jeffrey fluid forms the peripheral fluid layer. The resulting partial differential equations are solved for closed-form solutions after employing the assumption of long wavelength. The analysis delineated that increasing the constant secretion velocity, Darcy number, and Reynolds number leads to a decrease in the appropriate residue time of the core fluid layer and a reduction in the size of the secreting fluid bolus in the peripheral fluid layer. Eventually, the boluses completely disappear when the constant secretion velocity exceeds 3.0 Progesterone ([Formula: see text]) and estradiol ([Formula: see text]) directly regulate the transportation of the growing embryo, while luteinizing hormone (LH) and follicle-stimulating hormone (FSH), prolactin, anti-mullerian hormone (AMH), and thyroid-stimulating hormone (TSH) have an indirect effects. Based on the number and size of blastomeres, the percentage of fragmentation, and the presence of multinucleated blastomeres two groups were formed in an in vitro experiment. Out of 50 patients, 26 (76.5%) were pregnant in a group of the good quality embryos, and only 8 (23.5%) were in a group of the bad quality embryos. The transport of growing embryo in the human fallopian tube and preimplantation development of human embryos in in vitro are constraint by baseline hormones FSH, LH, prolactin, [Formula: see text], AMH, and TSH.

Progression to adrenocortical tumorigenesis in mice and humans through insulin-like growth factor 2 and ß-catenin.

Dysregulation of the WNT and insulin-like growth factor 2 (IGF2) signaling pathways has been implicated in sporadic and syndromic forms of adrenocortical carcinoma (ACC). Abnormal ß-catenin staining and CTNNB1 mutations are reported to be common in both adrenocortical adenoma and ACC, whereas elevated IGF2 expression is associated primarily with ACC. To better understand the contribution of these pathways in the tumorigenesis of ACC, we examined clinicopathological and molecular data and used mouse models. Evaluation of adrenal tumors from 118 adult patients demonstrated an increase in CTNNB1 mutations and abnormal ß-catenin accumulation in both adrenocortical adenoma and ACC. In ACC, these features were adversely associated with survival. Mice with stabilized ß-catenin exhibited a temporal progression of increased adrenocortical hyperplasia, with subsequent microscopic and macroscopic adenoma formation. Elevated Igf2 expression alone did not cause hyperplasia. With the combination of stabilized ß-catenin and elevated Igf2 expression, adrenal glands were larger, displayed earlier onset of hyperplasia, and developed more frequent macroscopic adenomas (as well as one carcinoma). Our results are consistent with a model in which dysregulation of one pathway may result in adrenal hyperplasia, but accumulation of a second or multiple alterations is necessary for tumorigenesis.

Multiple-Criteria Decision-Making (MCDM) techniques to study the behavior of dendrimers using topological indices.

Topological indices provide a mathematical language for capturing molecular structure, symmetry, and predicting properties. Dendrimers are microscopic bilaterally symmetrical molecules with a well-defined homogeneous nanoparticles structure, often consisting of a symmetric center, inner shell, and outer shell. In this work, first we compute some degree-based topological indices of Porphyrin (DnPn),Poly (Propyl) Ether Imine(PETIM), Zinc porphyrin (DPZn), and Polyamidoamine (PAMAM) dendrimers. Then, we use multi-criteria decision making (MCDM) techniques to establish the weighted evaluation of dendrimer classes based on certain topological indices. For weighted analysis we correlate the properties of benzene derivatives with topological invariants. Finally, based on the multi-criteria decision making techniques namely TOPSIS, SAW and MOORA method, we have ranked the dendrimer structures based on their properties.

Preclinical targeting of the type I insulin-like growth factor receptor in adrenocortical carcinoma.

CONTEXT: Drug therapy for adrenocortical carcinoma (ACC), a rare and lethal malignancy, is largely empirical and ineffective. New treatments directed at molecular targets critical to the pathophysiology of ACC may prove more efficacious. OBJECTIVE: The objective of the study was to profile human adrenal tumors and ACC cell lines to assess activated IGF signaling and determine the efficacy of two IGF receptor (IGF-1R) antagonists alone and in combination with mitotane. EXPERIMENTAL DESIGN: ACC cell lines that display or lack activated IGF signaling are used to assess the effects of two IGF-1R antagonists in cultured cells and ACC xenograft tumors. RESULTS: Transcriptional profiling data derived from DNA microarray analysis of human adrenal tumors implicate IGF2 as the single highest up-regulated transcript in the vast majority of carcinomas. We show that the majority of ACC cell lines tested display constitutive IGF ligand production and activation of downstream effector pathways. Both IGF-1R antagonists cause significant dose-dependent growth inhibition in ACC cell lines. Furthermore, we observe that mitotane, the first-line adrenolytic drug used in patients with ACC, results in enhanced growth inhibition when used in combination with the IGF-1R antagonists. We next examined the activity of IGF-1R antagonists against ACC xenografts in athymic nude mice. IGF inhibition markedly reduced tumor growth greater than that observed with mitotane treatment, and combination therapy with mitotane significantly enhanced tumor growth suppression. CONCLUSION: These findings establish a critical role of IGF signaling in ACC pathophysiology and provide rationale for use of targeted IGF-1R antagonists to treat adrenocortical carcinoma in future clinical trials.

Assessment of neuropharmacological activities of Pandanus foetidus (Pandanaceae) in mice.

The methanol extract of the leaves of Pandanus foetidus Roxb. (Pandanaceae) was assessed for neuropharmacological activities in mice using a number of experimental models. The extract dose-dependently inhibited acetic acid-induced writhing in mice when given at the doses of 250 and 500 mg/kg body weight. At the same dose levels, it significantly prolonged the pentobarbitone-induced sleeping time in mice, and showed mild to moderate central nervous system depressant activity when assessed by the hole cross and the open field tests in mice model. On the basis of these findings, it can be assumed that the extract exerts its depressant effect on the central nervous system in mice by interfering with the cortical function.

Molecular characterization and phylogeny of Shiga toxin-producing Escherichia coli isolates obtained from two Dutch regions using whole genome sequencing.

Shiga toxin-producing Escherichia coli (STEC) is one of the major causes of human gastrointestinal disease and has been implicated in sporadic cases and outbreaks of diarrhoea, haemorrhagic colitis and haemolytic uremic syndrome worldwide. In this study, we determined the molecular characteristics and phylogenetic relationship of STEC isolates, and their genetic diversity was compared to that of other E. coli populations. Whole genome sequencing was performed on 132 clinical STEC isolates obtained from the faeces of 129 Dutch patients with gastrointestinal complaints. STEC isolates of this study belonged to 44 different sequence types (STs), 42 serogenotypes and 14 stx subtype combinations. Antibiotic resistance genes were more frequently present in stx1-positive isolates compared to stx2 and stx1 + stx2-positive isolates. The iha, mchB, mchC, mchF, subA, ireA, senB, saa and sigA genes were significantly more frequently present in eae-negative than in eae-positive STEC isolates. Presence of virulence genes encoding type III secretion proteins and adhesins was associated with isolates obtained from patients with bloody diarrhoea. Core genome phylogenetic analysis showed that isolates clustered according to their ST or serogenotypes irrespective of stx subtypes. Isolates obtained from patients with bloody diarrhoea were from diverse phylogenetic backgrounds. Some STEC isolates shared common ancestors with non-STEC isolates. Whole genome sequencing is a powerful tool for clinical microbiology, allowing high-resolution molecular typing, population structure analysis and detailed molecular characterization of strains. STEC isolates of a substantial genetic diversity and of distinct phylogenetic groups were observed in this study.

The mosaic genome structure and phylogeny of Shiga toxin-producing Escherichia coli O104:H4 is driven by short-term adaptation.

Shiga toxin-producing Escherichia coli (STEC) O104:H4 emerged as an important pathogen when it caused a large outbreak in Germany in 2011. Little is known about the evolutionary history and genomic diversity of the bacterium. The current communication describes a comprehensive analysis of STEC O104:H4 genomes from the 2011 outbreak and other non-outbreak-related isolates. Outbreak-related isolates formed a tight cluster that shared a monophyletic relation with two non-outbreak clusters, suggesting that all three clusters originated from a common ancestor. Eight single nucleotide polymorphisms, seven of which were non-synonymous, distinguished outbreak from non-outbreak isolates. Lineage-specific markers indicated that recent partitions were driven by selective pressures associated with niche adaptation. Based on the results, an evolutionary model for STEC O104:H4 is proposed. Our analysis provides the evolutionary context at population level and describes the emergence of clones with novel properties, which is necessary for developing comprehensive approaches to early warning and control.

Patterns of stranding and mortality in common seals (Phoca vitulina) and grey seals (Halichoerus grypus) in The Netherlands between 1979 and 2008.

Pathological examination of stranded marine mammals provides information on the causes of mortality in their populations. Patterns of stranding and causes of death of dead-stranded seals on the Dutch coast were analyzed over a 30-year period (1979-2008). Stranding data (n=1,286) and post-mortem data (n=379) from common seals (Phoca vitulina) and grey seals (Halichoerus grypus) found dead, or that died before admission to rehabilitation, were obtained from the Seal Rehabilitation and Research Centre database. Data for the years 1988 and 2002, when mass mortality occurred due to phocine distemper virus epidemics, were excluded. Common seal stranding increased from one to nearly 100 per year over this period. This coincides with the increase in the number of common seals in Dutch waters over recent decades. Grey seal stranding increased gradually from one to about 40 per year over the period, reflecting recolonization of Dutch waters by this species. For both species, the trend in stranding of dead seals was found to be in line with that of seals observed in Dutch waters during aerial surveys and did not provide any indications of a relative change in the stranding rate of dead seals. The total monthly stranding rates peaked at more than 120 in June and July for common seals and at nearly 60 in January for grey seals. This coincides with the pupping periods of the two species. Besides phocine distemper, the most common causes of death in investigated common seals (n=286) were by-catch (confirmed and inferred) (19%), pup starvation (7%), intestinal volvulus (7%) and parasitic bronchopneumonia (6%). The most common causes of death in investigated grey seals (n=93) were by-catch (confirmed and inferred) (15%), pup starvation (11%) and trauma (5%). The relative occurrence of by-catch significantly decreased over time for grey seals, but not for common seals. Common seals were affected by infectious disease significantly more often than grey seals, mainly because of a higher occurrence of parasitic pneumonia. Phocine distemper caused mass mortalities among common seals, but not among grey seals. These findings in dead-stranded seals differ in part from those reported elsewhere in live-stranded seals, for which pup starvation and parasitic bronchopneumonia were the main causes of stranding. A substantial proportion of seals in Dutch waters die from causes related to human activity. Continued monitoring of stranding patterns and causes of death is warranted for early detection of changes and the possibility of taking timely management actions.

In search of adrenocortical stem and progenitor cells.

Scientists have long hypothesized the existence of tissue-specific (somatic) stem cells and have searched for their location in different organs. The theory that adrenocortical organ homeostasis is maintained by undifferentiated stem or progenitor cells can be traced back nearly a century. Similar to other organ systems, it is widely believed that these rare cells of the adrenal cortex remain relatively undifferentiated and quiescent until needed to replenish the organ, at which time they undergo proliferation and terminal differentiation. Historical studies examining cell cycle activation by label retention assays and regenerative potential by organ transplantation experiments suggested that the adrenocortical progenitors reside in the outer periphery of the adrenal gland. Over the past decade, the Hammer laboratory, building on this hypothesis and these observations, has endeavored to understand the mechanisms of adrenocortical development and organ maintenance. In this review, we summarize the current knowledge of adrenal organogenesis. We present evidence for the existence and location of adrenocortical stem/progenitor cells and their potential contribution to adrenocortical carcinomas. Data described herein come primarily from studies conducted in the Hammer laboratory with incorporation of important related studies from other investigators. Together, the work provides a framework for the emerging somatic stem cell field as it relates to the adrenal gland.