Small bowel diverticulosis: imaging appearances, complications, and pitfalls.

Diverticula of the small bowel can be categorised as true, with Meckel's being the only example, or false. False small bowel diverticula (SBD) are acquired through herniation of the internal layers of the bowel wall through the muscularis propria. Peri-ampullary duodenal diverticula are a well-recognised example; however, the importance of more distal SBD in the jejunum and ileum is underappreciated, and they are under-reported on cross-sectional imaging. SBD are a known cause of anaemia, malabsorption, and diarrhoea, and there are myriad complications of SBD and Meckel's diverticula, which range in severity from inflammation and perforation to haemorrhage, tumour formation, and obstruction. Before the advent of computed tomography (CT), SBD were readily diagnosed on fluoroscopic oral contrast studies; however, radiologists are less comfortable with their cross-sectional imaging appearances. This imaging review combines our experience of multiple proven cases, with illustrative diagrams and radiological images of SBD to provide distinct imaging characteristics, allowing for confident diagnosis of SBD and their numerous complications. We discuss the importance of SBD as a cause of benign, non-surgical pneumoperitoneum. We additionally provide important pitfalls to be aware of such as SBD masquerading as other abnormalities.

Biomarkers in Bladder Cancer Surveillance.

Aim: This is a narrative review with an aim to summarise and describe urinary biomarkers in the surveillance of non-muscle-invasive bladder cancer (NMIBC). It provides a summary of FDA-approved protein biomarkers along with emerging ones which utilise genetic, epigenetic and exosomal markers. We discuss the current limitations of the available assays. Background: Current guidelines advice a combination of cystoscopy, imaging,and urine cytology in diagnosis and surveillance. Although cytology has a high specificity, it is limited by low sensitivity particularly in low grade tumours. There are six FDA-approved urinary assays for diagnosis and surveillance of bladder cancer. They have shown to improve sensitivity and specificity to be used alongside cytology and cystoscopy but have a lower specificity in comparison to cytology and false positives often occur in benign conditions. Recent developments in laboratory techniques has allowed for use of markers which are RNA-, DNA-based as well as extracellular vesicles in the past decade. Methods: Using the PubMed/Medline search engines as well as Google Scholar, we performed an online search using the terms "bladder cancer," "non-muscle invasive bladder cancer," and "urine biomarkers" with filter for articles in English published up to May 2021. Systematic reviews and original data of clinical trials or observational studies which contributed to the development of the biomarkers were collated. Results: Biomarkers identified were divided into FDA-approved molecular biomarkers, protein biomarkers and gene-related biomarker with a table summarising the findings of each marker with the most relevant studies. The studies conducted were mainly retrospective. Due to the early stages of development, only a few prospective studies have been done for more recently developed biomarkers and limited meta-analyses are available.Therefore a detailed evaluation of these markers are still required to decide on their clinical use. Conclusion: Advancements of analytical methods in BC has driven the research towards non-invasive liquid-based biomarkers in adjunct to urine cytology. Further large prospective studies are required to determine its feasibility in a clinical setting as they are not effective when used in isolation as they have their limitation. With the ongoing pandemic, other than reduction in costs and increased accuracy, the need for biomarkers to cope with delay in cystoscopies in diagnosis and surveillance is crucial. Thus clinical trials with direct comparison is required to improve patient care.

Think before you prescribe: how dentistry contributes to antibiotic resistance.

Antibiotic resistance presents a daunting challenge to health professionals worldwide and has the potential to create major problems for modern health care, resulting in more medical expenditure, extended hospital stays and increased morbidity and mortality. Advanced genome sequencing technologies present a complex picture of resistance, extending our understanding beyond the pharmacotherapeutic interface between pathogens and antibiotics. This review discusses the global scope and scale of antibiotic resistance and contextualizes it for the dental practitioner, emphasizing the role we must play in limiting the progression of resistance through antibiotic stewardship and disease prevention.

Numerical analysis of an enhanced cooling rate cryopreservation process in a biological tissue.

Cryopreservation is the method of preservation of biological tissues for future references without causing significant damages to their physical and functional properties. This can be done by exposing them to very low cryogenic temperature that involves a greater heat removal rate. A two dimensional numerical model is developed to study the temperature distribution, cooling rate attained and movement of the freezing front during the cryopreservation process. The Pennes Bio-heat model is used for current study. The Finite Volume Method is employed for discretization of the governing differential equations while the Tri-Diagonal Matrix Algorithm is used to solve the discretized algebraic equations to find temperature distribution inside the domain. The Enthalpy-Porosity method is used to track the solid-liquid interfaces during the freezing process. The current model is first validated with the result of the existing literature. In the present work, freezing of tissue is done from one and two sides in two separate cases and the resulting temperature distribution inside the tissue and cooling rate in the two cases are compared. It is found that the freezing rate of tissue is enhanced about two times when it is freezed from two sides as compared to freezing from single side. Further, it is observed that a lower value of blood perfusion rate causes a lower value of the final temperature of the tissue after freezing. Thus, it can be concluded that the tissue with high blood perfusion rate is to be freezed in a lower cooling medium temperature. In the present condition, metabolic heat generation plays no significant role in the temperature distribution inside the healthy tissue.

Variants of katG, inhA and nat genes are not associated with mutations in efflux pump genes (mmpL3 and mmpL7) in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis from India.

To understand the impact of efflux pump genes such as mmpL3 and mmpL7 on isoniazid (INH) resistance and to correlate with presence or absence of mutations in essential genes of INH resistance (katG, inhA, and nat) in clinical isolates of Mycobacterium tuberculosis (M. tuberculosis). One hundred (75 resistant and 25 sensitive) clinical isolates of M. tuberculosis from India were selected for the study. The presence of mutations in specific regions of katG, inhA, and nat, efflux pump genes (mmpL3 and mmpL7) associated with INH resistance were analyzed using multiplex allele-specific polymerase chain reaction (MAS-PCR) and DNA sequencing methods, respectively. Substitution mutation AGC-ACC at codon 315 of the katG gene was detected in 65% of resistant isolates. Mutation (C-T at nucleotide position 15) in the inhA promoter region was seen in 22% of resistant isolates. Silent mutation (GGA to GGG) at codon 207 in the nat gene was found in three resistant isolates. No mutations were found in either of the efflux genes (mmpL3 and mmpL7) in any of the isolates. Of the 75 resistant isolates analyzed, 74% had mutation in katG and inhA genes. Thus, this report suggests that the role of mmpL3, mmpL7 and nat genes in INH resistance should not be overestimated in comparison to the primary contribution by katG and inhA in clinical isolates of M. tuberculosis. Further, this concise report is the first of its kind to our knowledge, to show the influence of efflux genes on INH resistance in relation to katG and inhA in clinical isolates of M. tuberculosis.

Activation of tumor suppressor LKB1 by honokiol abrogates cancer stem-like phenotype in breast cancer via inhibition of oncogenic Stat3.

Tumor suppressor and upstream master kinase Liver kinase B1 (LKB1) plays a significant role in suppressing cancer growth and metastatic progression. We show that low-LKB1 expression significantly correlates with poor survival outcome in breast cancer. In line with this observation, loss-of-LKB1 rendered breast cancer cells highly migratory and invasive, attaining cancer stem cell-like phenotype. Accordingly, LKB1-null breast cancer cells exhibited an increased ability to form mammospheres and elevated expression of pluripotency-factors (Oct4, Nanog and Sox2), properties also observed in spontaneous tumors in Lkb1-/- mice. Conversely, LKB1-overexpression in LKB1-null cells abrogated invasion, migration and mammosphere-formation. Honokiol (HNK), a bioactive molecule from Magnolia grandiflora increased LKB1 expression, inhibited individual cell-motility and abrogated the stem-like phenotype of breast cancer cells by reducing the formation of mammosphere, expression of pluripotency-factors and aldehyde dehydrogenase activity. LKB1, and its substrate, AMP-dependent protein kinase (AMPK) are important for HNK-mediated inhibition of pluripotency factors since LKB1-silencing and AMPK-inhibition abrogated, while LKB1-overexpression and AMPK-activation potentiated HNK's effects. Mechanistic studies showed that HNK inhibited Stat3-phosphorylation/activation in an LKB1-dependent manner, preventing its recruitment to canonical binding-sites in the promoters of Nanog, Oct4 and Sox2. Thus, inhibition of the coactivation-function of Stat3 resulted in suppression of expression of pluripotency factors. Further, we showed that HNK inhibited breast tumorigenesis in mice in an LKB1-dependent manner. Molecular analyses of HNK-treated xenografts corroborated our in vitro mechanistic findings. Collectively, these results present the first in vitro and in vivo evidence to support crosstalk between LKB1, Stat3 and pluripotency factors in breast cancer and effective anticancer modulation of this axis with HNK treatment.

Metagenomic Insights into Transferable Antibiotic Resistance in Oral Bacteria.

Antibiotic resistance is considered one of the greatest threats to global public health. Resistance is often conferred by the presence of antibiotic resistance genes (ARGs), which are readily found in the oral microbiome. In-depth genetic analyses of the oral microbiome through metagenomic techniques reveal a broad distribution of ARGs (including novel ARGs) in individuals not recently exposed to antibiotics, including humans in isolated indigenous populations. This has resulted in a paradigm shift from focusing on the carriage of antibiotic resistance in pathogenic bacteria to a broader concept of an oral resistome, which includes all resistance genes in the microbiome. Metagenomics is beginning to demonstrate the role of the oral resistome and horizontal gene transfer within and between commensals in the absence of selective pressure, such as an antibiotic. At the chairside, metagenomic data reinforce our need to adhere to current antibiotic guidelines to minimize the spread of resistance, as such data reveal the extent of ARGs without exposure to antimicrobials and the ecologic changes created in the oral microbiome by even a single dose of antibiotics. The aim of this review is to discuss the role of metagenomics in the investigation of the oral resistome, including the transmission of antibiotic resistance in the oral microbiome. Future perspectives, including clinical implications of the findings from metagenomic investigations of oral ARGs, are also considered.

HOXA5 determines cell fate transition and impedes tumor initiation and progression in breast cancer through regulation of E-cadherin and CD24.

Loss of HOXA5 expression occurs frequently in breast cancer and correlates with higher pathological grade and poorer disease outcome. However, how HOX proteins drive differentiation in mammalian cells is poorly understood. In this paper, we investigated cellular and molecular consequences of loss of HOXA5 in breast cancer, and the role played by retinoic acid in HOXA5 function. Analysis of global gene expression data from HOXA5-depleted MCF10A breast epithelial cells, followed by validation, pointed to a role for HOXA5 in maintaining several molecular traits typical of the epithelial lineage such as cell-cell adhesion, tight junctions and markers of differentiation. Depleting HOXA5 in immortalized MCF10A or transformed MCF10A-Kras cells reduced their CD24+/CD44lo population, enhanced self-renewal capacity and reduced expression of E-cadherin (CDH1) and CD24. In the case of MCF10A-Kras, HOXA5 loss increased branching and protrusive morphology in Matrigel, all features suggestive of epithelial to basal transition. Further, orthotopically implanted xenografts of MCF10A-Kras-scr grew as well-differentiated pseudo-luminal carcinomas, while MCF10A-Kras-shHOXA5 cells formed aggressive, poorly differentiated carcinomas. Conversely, ectopic expression of HOXA5 in aggressive SUM149 or SUM159 breast cancer cells reversed the cellular and molecular alterations observed in the HOXA5-depleted cells. Retinoic acid is a known upstream regulator of HOXA5 expression. HOXA5 depletion in MCF10A cells engineered to express doxycycline-induced shHOXA5 slowed transition of cells from a less differentiated CD24-/CD44+ to the more differentiated CD24+/CD44+ state. This transition was promoted by retinal treatment, which upregulated endogenous HOXA5 expression and caused re-expression of occludin and claudin-7 (CLDN7). Expression of CDH1 and CD24 was transcriptionally upregulated by direct binding of HOXA5 to their promoter sequences as demonstrated by luciferase and ChIP analyses. Thus, loss of HOXA5 in mammary cells leads to loss of epithelial traits, an increase in stemness and cell plasticity, and the acquisition of more aggressive phenotypes.

Dynamic nuclear polarization of biocompatible (13)C-enriched carbonates for in vivo pH imaging.

A hyperpolarization technique using carbonate precursors of biocompatible molecules was found to yield high concentrations of hyperpolarized (13)C bicarbonate in solution. This approach enabled large signal gains for low-toxicity hyperpolarized (13)C pH imaging in a phantom and in vivo in a murine model of prostate cancer.

Mitigation of environmental impacts due to ghat road formation in Palamalai Hills, South India, by optimizing cut and fill volumes using GPS and GIS techniques.

Formation of new roads generally brings about adverse impact on the environment, and in the case of hill roads, the impact is diverse and effective measures are required to mitigate it. The common problems in hill road formation are tree cutting, destruction of canopies, change in land use pattern, soil erosion, slope instability, induced landslides, invasion of foreign species, and so on. Removal of trees and vegetations causes rapid soil erosion, landslides, and invasion of foreign species posing danger to the survival of weak native species. Dumping of surplus earth materials on the valley side poses a significant threat to the environment as it would cause induced landslides. Using the cut earth for filling in road formation and dumping, the surplus cut earth in safe locations will reduce environmental degradation considerably. Conventionally, hill road alignments are finalized using traditional survey methods using ghat tracer, compass, and leveling surveys which require enormous complicated field and office works. Any revision to reduce the quantum of earthwork is difficult in this method due to its complex nature. In the present study at Palamalai Hills, South India, an alignment for a length of 7.95 km was prepared by traditional methods using ghat tracer and total station instruments for survey works. The earthwork quantities were ascertained from the longitudinal profile of the alignment. A GPS survey was also conducted along the alignment to examine its utility in alignment modification. To modify the stretches, where the earthwork cutting and filling are above normal and unbalanced and result in surplus earth, repeated GPS surveys were conducted along different paths to optimize the earthwork. The earthwork quantities of the original alignment were analyzed, and its correlation with environmental effect and the usefulness of the GPS survey in this task are presented in this paper.

Areca nut chewing in an expatriate population in Sydney: report of two cases.

Areca nut (betel nut) consumption occurs in a variety of forms, either on its own or with the addition of a number of products. This habit is prevalent in the Indian Subcontinent and South-East Asia. Recent immigration statistics indicate that 30% of new arrivals in Australia are from these geographical regions and are known to perpetuate this custom long after migration. The objective of this paper is to highlight the variety of oral presentations that may occur as a result of areca nut consumption in these particular demographic subgroups. Dental practitioners must be familiar with the wide spectrum of oral lesions that may present in this setting. More significantly, they must be aware that some of these lesions possess the potential for malignant transformation and hence require more specific management. Best practice mandates that dental practitioners in a multicultural society must: (1) be capable of recognizing the expatriate populations in which this custom is widely practised; (2) incorporate this particular line of questioning into the routine risk factor analysis that is undertaken for every patient from these particular sub-populations; and (3) institute appropriate referral and follow-up of these lesions if required.

Removal of chromium using Rhizobium leguminosarum.

The chromium (Cr(III) and Cr(VI)) removal capability of Rhizobium leguminosarum was checked by estimating the amount of chromium in the medium before and after inoculation. To determine the efficiency of R. leguminosarum in removal of chromium, the influence of physical and chemical parameters such as temperature, pH and different concentrations (0.1-1.0 mM) of trivalent (Cr(III)) and hexavalent (Cr(VI)) chromium were studied. The chromium removal in aqueous solution by different size of active and inactivated biomass and immobilized cells of R. leguminosarum in a packed-bed column was also carried out. Results showed that in a medium containing up to 0.5 mM concentration of both Cr(III) and Cr(VI), R. leguminosarum showed optimal growth. The maximum chromium removal was at pH 7.0 and 35°C. Active biomass removed 84.4 ± 3.6% of Cr(III) and 77.3 ± 4.3% of Cr(VI) in 24 h of incubation time. However, inactivated biomass removed maximum chromium after 36 h of incubation. Immobilized bacterial cells in a packed-bed column removed 86.4 ± 1.7% of Cr(III) and 83.8 ± 2.2% of Cr(VI) in 16 and 20 h of incubation time, respectively.

Flexible sigmoidoscopy does not significantly increase polyp and cancer detection yield when used to supplement CT colonography.

BACKGROUND AND AIMS: Flexible sigmoidoscopy (FS) increases polyp and carcinoma detection in addition to double contrast barium enema (DCBE). However, CT colonography (CTC) is now the preferred technique. Our aim was to explore whether FS increases polyp and carcinoma detection rates when used in addition to CTC. METHODS: Patients who underwent FS and CTC between 2007 and 2009 were included and data were collected from patient records. Yields of polyp, adenoma and carcinoma detection were calculated for FS and CTC. RESULTS: In a cohort of 294 patients, CTC detected 36 patients with carcinomas while FS detected 28. One rectal cancer not seen on CTC was diagnosed by FS. Polyps were seen by CTC in 66 and FS in 45 patients. In 5 patients FS found polyps that were not detected by CTC; 3 of which were small adenomas. FS detected extra adenomas or carcinomas in 1.36% (4/294). Adding FS to CTC neither increased the cancer nor the polyp detection yield significantly. CONCLUSIONS: This first study investigating the use of FS in addition to CTC detected little additional pathology. The routine use of FS as a supplement to CTC for adenoma and carcinoma detection is of questionable utility.

Malignant tumours of the jaws.

Almost all variants of malignant primary and secondary tumours of bone have been described as occurring within the jaws. Odontogenic carcinomas and sarcomas are peculiar to the jawbones and are distinctly uncommon. Non-odontogenic tumours in comparison arise with more frequency, yet the maxilla and mandible remain unusual sites for most primary and secondary non-odontogenic tumours of bone. The most commonly occurring primary bone tumours affecting the jaws include osteosarcoma, Burkitt's lymphoma and multiple myeloma, while secondary or metastatic tumours to the jaws are rare in contrast to the remainder of the skeleton.

HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs.

Most cases of breast cancer (BrCa) mortality are due to vascular metastasis. BrCa cells must intravasate through endothelial cells (ECs) to enter a blood vessel in the primary tumor and then adhere to ECs and extravasate at the metastatic site. In this study we demonstrate that inhibition of hypoxia-inducible factor (HIF) activity in BrCa cells by RNA interference or digoxin treatment inhibits primary tumor growth and also inhibits the metastasis of BrCa cells to the lungs by blocking the expression of angiopoietin-like 4 (ANGPTL4) and L1 cell adhesion molecule (L1CAM). ANGPTL4 is a secreted factor that inhibits EC-EC interaction, whereas L1CAM increases the adherence of BrCa cells to ECs. Interference with HIF, ANGPTL4 or L1CAM expression inhibits vascular metastasis of BrCa cells to the lungs.

The adult cystic fibrosis patient with abdominal pain: what the radiologist needs to know.

As the life expectancy of cystic fibrosis (CF) patients continues to increase, abdominal manifestations of CF are increasingly being encountered by clinicians and radiologists. Imaging plays an important role in the evaluation of adult CF patients with abdominal pain as a cause is often not discernable clinically. Accurate diagnosis is crucial in these patients as some causes may be managed conservatively, whilst others may require surgical intervention. In this review, we describe clinical presentation, imaging findings, and management of adult CF patients presenting with abdominal pain.