Transcutaneous fluorescence spectroscopy: development and characterization of a compact, portable, and fiber-optic sensor.

Significance: The integrity of the intestinal barrier is gaining recognition as a significant contributor to various pathophysiological conditions, including inflammatory bowel disease, celiac disease, environmental enteric dysfunction (EED), and malnutrition. EED, for example, manifests as complex structural and functional changes in the small intestine leading to increased intestinal permeability, inflammation, and reduced absorption of nutrients. Despite the importance of gut function, current techniques to assess intestinal permeability (such as endoscopic biopsies or dual sugar assays) are either highly invasive, unreliable, and/or difficult to perform in certain patient populations (e.g., infants). Aim: We present a portable, optical sensor based on transcutaneous fluorescence spectroscopy to assess gut function (in particular, intestinal permeability) in a fast and noninvasive manner. Approach: Participants receive an oral dose of a fluorescent contrast agent, and a wearable fiber-optic probe detects the permeation of the contrast agent from the gut into the blood stream by measuring the fluorescence intensity noninvasively at the fingertip. We characterized the performance of our compact optical sensor by comparing it against an existing benchtop spectroscopic system. In addition, we report results from a human study in healthy volunteers investigating the impact of skin tone and contrast agent dose on transcutaneous fluorescence signals. Results: The first study with eight healthy participants showed good correlation between our compact sensor and the existing benchtop spectroscopic system [correlation coefficient (r)>0.919, p<0.001]. Further experiments in 14 healthy participants revealed an approximately linear relationship between the ingested contrast agent dose and the collected signal intensity. Finally, a parallel study on the impact of different skin tones showed no significant differences in signal levels between participants with different skin tones (p>0.05). Conclusions: In this paper, we demonstrate the potential of our compact transcutaneous fluorescence sensor for noninvasive monitoring of intestinal health.

Sinonasal and Infratemporal Schwannoma: Rare Case Report with Literature Review.

Schwann cells are responsible for the production of the myelin sheath around the axons of the peripheral nervous system. Benign neoplasms which originate from Schwann cells are hence termed Schwannomas or Neurilemmomas. They present as slow-growing, solitary, encapsulated, benign masses usually in association with nerve trunks. Schwannomas are relatively rare tumors with 25-45% occurring in the head and neck region. These case reports aim to describe the presentations, work-up, and treatment of two patients with head and neck schwannoma in atypical locations. Both patients had a history of gradually increasing swelling, the first originating from the sino-nasal region and the second from the temporal/ infratemporal region. Complete surgical excision of the tumor was done in both cases with no reported recurrence at 18 months follow-up. The final diagnosis was made based on histopathology and immunohistochemistry findings. Schwannomas often present a diagnostic dilemma and should be considered a possibility in all head and neck tumors. Recurrence is rare.

A global analysis on the differential regulation of RNA binding proteins (RBPs) by TNF-α as potential modulators of metabolic syndromes.

Metabolic syndrome (MetS) is associated with a group of conditions, which enhances the risk of diabetes, heart diseases and stroke in the affected individuals. Earlier reports from our lab have shown that Tumor necrosis factor-α (TNF-α) significantly modulates the expression of 56 genes at the alternative splicing level which are involved in various signaling and metabolic pathways (MetS genes) connected to MetS. These MetS genes were predicted to interact with various RNA-binding proteins (RBPs) when exposed to TNF-α, resulting changes in their alternative splicing patterns. Here we are presenting data of an RNA-Seq analysis, which identified 1218 unique, and significantly regulated genes by TNF-α, 15% of which are RBPs . Among the 1218 genes, 204 genes have been identified as MetS genes by the ingenuity pathway analysis, and 10% of the MetS genes are found as RBPs. Our results also show that TNF-α changes the phosphorylation status of certain RBPs such as SR proteins, crucial players in alternative splicing, possibly via changing the activation status of certain upstream signaling molecules which also act as upstream kinases for these proteins. Taken together, these findings suggest that TNF-α influences the regulation of the RBPs at the various levels for their expression, which may lead to the alteration of the splicing pattern of the MetS genes. MetS genes acting as RBPs and are modulated by TNF-α, predict the existence of highly interconnected mechanisms which require further analysis to understand their dual roles on the onset of these diseases.

Sporadic pediatric colorectal carcinoma without known genetic predisposition - Defying the dictum: Learning lesson with review of the literature.

Pediatric colorectal carcinomas are extremely rare with an incidence of nearly 1.3 per million. Diagnosis is usually delayed following a lack of suspicion at this age. Increasing incidence as well as awareness provides an insight into the disease entity. Two cases of childhood colorectal carcinoma, one in an 11 and another in a 19-year-old boy are presented. However, they have been reparted to carry a forarable outcome. Both the cases showed mucin and signet ring cells which indicates an aggressive behavior. The presentation highlights the clinical characteristics and genetic implications in most of the patients. However, both our cases did not show any predisposing or genetic predisposition. These cases are presented to make aware the readers as to how the common dictum can be reversed and adolescents can also be affected by cancer, a disease of the elderly. Early diagnosis can provide a better management and prognosis.

Global analysis of RNA-protein interactions in TNF-α induced alternative splicing in metabolic disorders.

In this report, using the database of RNA-binding protein specificities (RBPDB) and our previously published RNA-seq data, we analyzed the interactions between RNA and RNA-binding proteins to decipher the role of alternative splicing in metabolic disorders induced by TNF-α. We identified 13 395 unique RNA-RBP interactions, including 385 unique RNA motifs and 35 RBPs, some of which (including MBNL-1 and 3, ZFP36, ZRANB2, and SNRPA) are transcriptionally regulated by TNF-α. In addition to some previously reported RBPs, such as RBMX and HuR/ELAVL1, we found a few novel RBPs, such as ZRANB2 and SNRPA, to be involved in the regulation of metabolic syndrome-associated genes that contain an enrichment of tetrameric RNA sequences (AUUU). Taken together, this study paves the way for novel RNA-protein interaction-based therapeutics for treating metabolic syndromes.

Protocol for a cluster randomised trial in Madhya Pradesh, India: community health promotion and medical provision and impact on neonates (CHAMPION2); and support to rural India's public education system and impact on numeracy and literacy scores (STRIPES2).

BACKGROUND: Rural areas of India exhibit high neonatal mortality, and low literacy and numeracy. We assess the effect of a complex package of health interventions on neonatal survival and the effect of out-of-school-hours teaching on children's literacy and numeracy in rural Madhya Pradesh. METHODS/DESIGN: This is a cluster-randomised controlled trial with villages (clusters) receiving either a health (CHAMPION2) or education (STRIPES2) intervention. Building on the design of the earlier CHAMPION/STRIPES trial, villages receiving the health intervention are controls for the education intervention and vice versa. The clusters are 196 villages in Satna district, Madhya Pradesh, India: each is at least 5 km from a Community Health Centre, has a population below 2500, and has at least 15 children eligible for the education intervention. The participants in CHAMPION2 are resident married women younger than 50 years of age who had not undergone a family planning operation, provided they are enumerated pre-randomisation or marry a man enumerated pre-randomisation. The participants in STRIPES2 are resident children born 16 June 2010 to 15 June 2013, not in school before the 2018-2019 school year and intending to enrol in first grade in 2018-2019 or 2019-2020. DISCUSSION: In CHAMPION2, the NICE Foundation will deliver a 3.5-year programme comprising Accredited Social Health Activists or village health workers and midwives promoting health knowledge and providing antenatal, postnatal, and neonatal healthcare; community mobilisation; referrals to appropriate government health facilities; and a health education campaign. In STRIPES2, the Pratham Education Foundation will deliver a programme of village-based, before/after school support focusing on literacy and numeracy. As controls, the CHAMPION2 control villages will receive the usual health services (plus the STRIPES2 intervention). STRIPES2 control villages will receive the usual education services (plus the CHAMPION2 intervention). The primary outcome in CHAMPION2 is neonatal mortality. Secondary outcomes include antenatal, delivery, immediate neonatal and postnatal care practices, maternal mortality, stillbirths, early neonatal deaths, perinatal deaths, health knowledge, hospital admissions, maternal blood transfusions, and cost effectiveness. The primary outcome in STRIPES2 is a composite literacy and numeracy test score. Secondary outcomes include separate literacy and numeracy scores, reported school enrolment and attendance, parents' engagement with children's learning, and cost effectiveness. Independent research and implementation teams will conduct the trial. Trial Steering and Data Monitoring Committees, with independent members, will supervise the trial. TRIAL REGISTRATION: Clinical Trial Registry of India: CTRI/2019/05/019296. Registered on 23 May 2019. http://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=31198&EncHid=&modid=&compid=%27,%2731198det%27.

Molecular mechanisms of tobacco induced oral and oropharyngeal cancer: Results of a tissue microarray and immunohistochemistry-based study from a tertiary cancer center in India.

BACKGROUND: It is well established that chronic exposure to tobacco induces head and neck cancers but the exact etiopathogenesis is not known. Though studies have shown expression of TIMP1, EPS8 and AXL in cancers, their role in tobacco-induced cancers is not known. We aimed this study to evaluate the role of these molecules in oral and oropharyngeal squamous cell cancers (SCC). MATERIALS AND METHODS: In this single institutional study, 31 patients of oral and oropharyngeal SCC with history of chewing tobacco were included. Smokers were excluded from the study. After informed consent biopsies were taken from affected and contralateral normal mucosa. Paraffin blocks were made and tissue microarray (TMA) were constructed using these blocks. Immunohistochemistry (IHC) for TIMP1, EPS8, AXL kinase was carried out on these tissue microarrays. The intensity of staining was scored from 0 to 3+, related to expression of each of the three molecules. RESULTS: The expression of TIMP1, EPS8 and AXL kinase was significantly more in the cancerous mucosa versus non-cancerous mucosa (P = 0.000 in all three) in oral and oropharyngeal SCC exposed to chewing tobacco. CONCLUSION: Immunohistochemical expression of these molecular markers in oral and oropharyngeal SCC correlated with their molecular based studies. Significant IHC expression of TIMP1, EPS8 and AXL establishes their role in the pathogenesis of oral and oropharyngeal squamous cell carcinomas. Novel targeted therapies may be researched that can detect and target these molecules at an earlier stage of pathogenesis of these tumors.

A Rare Case of Mucoepidermoid Carcinoma of Parotid with Mandibular Metastasis.

Mucoepidermoid carcinoma is the most common malignant tumor of salivary gland. Majority of the salivary gland tumors arise in parotid gland with maximum being of benign nature. Although Mucoepidermoid carcinoma accounts for less than 10% of all tumors of the salivary gland, it constitutes approximately 30% of all malignant tumors of the salivary gland. It is characterized by a mixed pattern of the two main cell types: epidermoid and mucus-producing cells. Metastasis from salivary gland malignancy is infrequent and predominantly found in bone, lung, liver and lymph nodes. We are presenting a rare case of metastasis of mucoepidermoid carcinoma of parotid gland to the contralateral mandible.

Finding small molecules with pan-serotype activity to target Dengue non-structural protein 1.

Dengue virus (DENV) is a mosquito-borne flavivirus which causes Dengue fever and severe Dengue. It exists as four antigenically different serotypes that are further classified into genotypes with varying degrees of pathogenicity. The non-structural protein 1 (NS1) of DENV has an important role in viral replication and its pathogenesis. NS1 is also considered as an important diagnostic marker for Dengue pathogenesis. To the best of our knowledge, there are no attempts to explore small molecule drugs to target the NS1 of all the serotypes. Here, we have taken the DENV 2 NS1 crystal structure as a reference to model the NS1 structure of the other three serotypes. Once the active site of the NS1 is identified, virtual screening of plant flavonoids is carried out against the NS1 of all the four serotypes. The top 200 molecules in the library with high binding affinities are further analysed to find the common ones having comparable affinities to all the four serotypes. The predicted common flavonoids are subjected to ADMET profiling to further select the most potential molecules that can be used to target NS1 of all the four serotypes.

Thermal picks for anchoring on icy moons.

Europa, Enceladus, and other icy moons are exciting science targets, but our capabilities to adequately explore these planetary bodies needs to be developed. Gripping the surface ice may aid the stability and mobility of surface landers and mobile explorers that are sent to the surface of an icy moon. This paper presents an approach to anchoring into the surface of an icy moon using a heated pick. The proposed thermodynamic approach contrasts with the traditional mechanical approach to inserting terrestrial ice anchors. This thermodynamic approach maintains the ice structure to provide a reliable hold. The low temperatures and lack of a significant atmosphere on most of the icy moons cause surface conditions to stay below the triple point of water, the primary constituent of the surface ice for both Europa and Enceladus. Under these conditions the surface water ice will sublimate when sufficiently heated. The thermal pick concept presented in this paper is used to study the nature of the sublimation that results from forced insertion of an object into ice, which could then be used as an anchor for stability and mobility. While the surfaces of the icy moons are composed primarily of water ice at cryogenic and vacuum conditions, the nature of a sublimation process can be more readily examined with frozen CO2, which sublimates under atmospheric conditions. This paper explores the physical phenomena and thermodynamic design considerations of a heated device that uses a sublimation based insertion into frozen CO2 under atmospheric conditions. This approach was found to allow for proper insertion of thermal picks with energetic efficiencies of up to 90%.

Human epidermal growth factor receptor 2 neu expression in head and neck squamous cell cancers and its clinicopathological correlation: Results from an Indian cancer center.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)/neuprotooncogene (neu) is a proven molecular prognostic marker in breast, ovarian, gastric, and ovarian cancers. In head-and-neck cancers, varied expression is documented and therefore its prognostic role is debatable. AIM OF THE STUDY: To find the rate of overexpression of HER2/neu in head-and-neck cancers and to understand its prognostic role by evaluating its association with nodal stage and overall stage of the patient. METHODOLOGY: A total of 70 surgically resected cases of head-and-neck cancers were evaluated for expression of HER2/neu by immunohistochemistry. Scoring was done according to the American Society of Clinical Oncologists/College of American Pathologistsguidelines for Her2/neu testing in breast cancer. RESULTS: Of the 70 cases studied, 57 were of oral cavity and 13 were laryngeal squamous cell cancers and 14 (20%) were Her2/neu positive. On correlating the expression of HER2/neu in T1/T2 (41 cases) versus T3/T4 (27 cases), the P value was found to be 0.8273 which was statistically insignificant. Furthermore, no statistically significant difference in expression of HER2/neu was found in between node negative and node positive cases (49 vs. 19 cases, respectively), with P = 0.512. CONCLUSION: In the current settings, HER2/neu is not found to be a prognostic marker in head-and-neck cancers. Standard immunohistochemistry staining protocols need to be established like in breast cancers to aid uniform reporting and further evaluate the role of this important protooncogene in head-and-neck cancers.

Lipofibromatous hamartoma of the digital branches of the median nerve presenting as carpal tunnel syndrome: A rare case report with review of the literature.

Lipofibromatous hamartoma (LFH) is a rare, benign fibrofatty tumor composed of a proliferation of mature adipocytes within peripheral nerves, which form a palpable neurogenic mass. It affects the median nerve in 66-80% of cases, causing pain and sensory and motor deficits in the affected nerve distribution. Patients typically present with gradually enlarging nontender lesions in the distribution of the affected nerve. The lesion is also seen to be associated with macrodactyly. The pathophysiology of LFH is unknown. Treatment of LFH is based on symptoms of the condition. Histopathology is characteristic. We present a case of young male diagnosed as lipofibromatous hamartoma of the median nerve involving the right index finger. The case is presented due to its rarity.

Clinicoradiological Images of a Rare Type of Lumbar Hernia.

A surgeon will rarely see a case of lumbar hernia in his lifetime. They are usually divided into superior and inferior types, but in cases of huge hernias where anatomical delineation is not possible, they are called as diffuse. Further classification into primary and secondary types (on the basis of etiology) and congenital and acquired types is done. Evisceration in a lumbar hernia can be present due to secondary causes but never spontaneously. This is therefore probably the first reported case of a primary eviscerated diffuse lumbar hernia.

Axillary apocrine adenocarcinoma in a young male suspected initially on fine-needle aspiration cytology.

Primary apocrine sweat gland adenocarcinomas are a rare entity, with only a few case reports so far. Many of these carcinomas are slow-growing with a high recurrence rate. A distinct cytological diagnosis can be made, and metastatic adenocarcinomas are always considered as a differential diagnosis on cytology. Our case was a 35-year-old male who presented with a discharging axillary sinus and swelling for the past 1 year. A clinical suspicion of tuberculous sinus was raised that however, remained unsupported by laboratory investigations. There was quite a high suspicion of apocrine adenocarcinoma on cytological examination that was confirmed by histopathology and immunohistochemistry. The patient was successfully treated with total excision and a wide margin. We report this case in view of its rarity and its occurrence in a 35-year-old young male, and emphasize that an initial cytological suspicion should be raised for primary apocrine adenocarcinoma in case of an axillary tumor, especially keeping in consideration the poor prognosis of the same and chances of early metastasis.

Tubercular thyroiditis with multinodular goitre with adenomatous hyperplasia: a rare coexistence.

A 32-year-old Indian woman presented with swelling in the anterior part of the neck for the last 3 years. Clinical and radiological examination and fine needle aspiration cytology suggested the diagnosis of multinodular goitre. A subtotal thyroidectomy was performed by the surgeon and the specimen was submitted for the final diagnosis. Histological examination of the specimen revealed multiple caseating tubercular granulomas coexistent with multinodular goitre and adenomatous hyperplasia. The sections demonstrated acid-fast tubercle bacteria, confirming the diagnosis of tubercular thyroiditis. This case emphasises that tubercular thyroiditis should always be considered in patients with thyroid swelling or nodule, in countries where the prevalence of tuberculosis is high.