Thyroid ultrasound is the best prevalence indicator for assessment of iodine deficiency disorders: a study in rural/tribal schoolchildren from Gujarat (Western India)

OBJECTIVES: (i) To assess the severity of iodine deficiency disorders (IDD), (ii) to determine the aetiology of IDD in Gujarat, (iii) to identify the best prevalence indicator of IDD, and (iv) to compare thyroid volume (TV) results with the WHO International reference. METHODS: Five hundred and thirty schoolchildren (6-15 years) were studied from two districts (Baroda and Dang) and data were collected on dietary habits and parameters such as height, weight, thyroid size by palpation and ultrasonography, urinary iodine (UI), and blood thyroid stimulating hormone (TSH). Drinking water was analyzed for iodine content and food articles for goitrogens. RESULTS: In Gujarat children median UI (interquartile range)=56 (30-96)microg/l, mean TSH=1.71 +/- 2.10mU/l, goiter by palpatio n = 30%, and median TV = 27.8 (23-35)ml. Females had lower median UI (48 (27-82) microg/l) and higher mean TSH levels (2.0 +/- 2.5mU/l) than males. Applying the WHO ultrasonography reference to Gujarat children resulted in an enlarged TV-for-body surface area in almost 100% of subjects. Ninety-nine percent of females and 95% of males had enlarged TV-for-age. Three to eight times larger TV were seen in all subjects as compared with European children. Dang children were severely malnourished. Flavonoids like vitexin, glucosyl vitexin and apigenin were detected in pearl millet. Apigenin was never identified in pearl millet. Dang district water was lacking in iodine content. CONCLUSIONS: IDD is a severe public health problem in Gujarat. Baroda district is a new pocket of IDD. High amounts of dietary flavonoids in Baroda and Dang districts, and lack of iodine in Dang water, account for IDD. TV measurement by ultrasound is the best prevalence indicator of IDD.     

When does the brain inform the eyes whether and where to move? An EEG study in humans

The current study addressed when in the course of stimulus processing, and in what brain areas, activity occurs that supports the interpretation of cues that signal the appropriateness of different and competing behaviors. Twelve subjects completed interleaved no-go-, pro-, and antitrials, whereas 64-channel electroencephalography was recorded. Principle component and distributed source analyses were used to evaluate the spatial distribution and time course of cortical activity supporting cue evaluation and response selection. By 158 ms poststimulus, visual cortex activity was lower for no-go trials than it was for both pro- and antitrials, consistent with an early sensory filter on the no-go cue. Prefrontal cortex (PFC) activity at 158 ms was highest during antitrials, consistent with this brain region's putative involvement in executive control. At 204 ms poststimulus, however, PFC activity was the same for pro- and antitrials, consistent with an ostensible role in response selection. PFC activity at 204 ms also was robustly inversely correlated (r = -0.75) with visual cortex activity on antitrials, perhaps indicating top-down modulation of early sensory processing that would decrease the probability of an error response. These data highlight how a distributed neural architecture supports the evaluation of stimuli and response choices.     

Rapid diagnosis and tumor margin assessment during pancreatic cancer surgery with the MasSpec Pen technology

Intraoperative delineation of tumor margins is critical for effective pancreatic cancer surgery. Yet, intraoperative frozen section analysis of tumor margins is a time-consuming and often challenging procedure that can yield confounding results due to histologic heterogeneity and tissue-processing artifacts. We have previously described the development of the MasSpec Pen technology as a handheld mass spectrometry–based device for nondestructive tissue analysis. Here, we evaluated the usefulness of the MasSpec Pen for intraoperative diagnosis of pancreatic ductal adenocarcinoma based on alterations in the metabolite and lipid profiles in in vivo and ex vivo tissues. We used the MasSpec Pen to analyze 157 banked human tissues, including pancreatic ductal adenocarcinoma, pancreatic, and bile duct tissues. Classification models generated from the molecular data yielded an overall agreement with pathology of 91.5%, sensitivity of 95.5%, and specificity of 89.7% for discriminating normal pancreas from cancer. We built a second classifier to distinguish bile duct from pancreatic cancer, achieving an overall accuracy of 95%, sensitivity of 92%, and specificity of 100%. We then translated the MasSpec Pen to the operative room and predicted on in vivo and ex vivo data acquired during 18 pancreatic surgeries, achieving 93.8% overall agreement with final postoperative pathology reports. Notably, when integrating banked tissue data with intraoperative data, an improved agreement of 100% was achieved. The result obtained demonstrate that the MasSpec Pen provides high predictive performance for tissue diagnosis and compatibility for intraoperative use, suggesting that the technology may be useful to guide surgical decision-making during pancreatic cancer surgeries.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, with a 5-y survival rate of 9% for all stages (1). Among patients with resectable tumors, surgical resection with microscopically negative margins is required for prolonged disease-free survival (2). Thus, differentiating normal tissue from tumor is the cornerstone of effective pancreatic oncologic surgery (3, 4). In practice, delineation of pancreatic resection margins is difficult and variable. Tumor margin status is commonly assessed intraoperatively by microscopic histopathological evaluation of frozen sections prepared from excised pancreatic neck and common bile duct margins prior to completion of the operation (5, 6). However, artifacts on tissue histology from frozen section preparation complicates histopathologic evaluation, further accentuated by the complex pathology of PDAC, with high desmoplastic stromal content and chronic pancreatitis (CP) at the pancreatic resection margins as well as inflammation induced by surgical manipulation of bile duct tissue–mimicking tumor (7, 8). Moreover, the reported accuracy of frozen section analysis is variable center-to-center and depends on the methodology, skillset, and subspecialty of the pathologist on call (9–12).Several optical and molecular technologies are being developed with the expectation of improving pancreatic cancer detection during surgery (SI Appendix, Text) (13–15). In particular, mass spectrometry (MS) technologies are powerful for investigating molecular differences between normal and cancerous tissues with high sensitivity, chemical specificity, and speed and have also been explored for surgical use and margin evaluation (16). Desorption electrospray ionization (DESI) MS, for example, has been used to investigate molecular differences between normal and cancerous tissues ex vivo cancerous and normal tissue sections (17–19). In particular, Zare and coworkers applied DESI-MS imaging to analyze the metabolic and lipid profiles of adjacent histologic tissue sections of margin regions collected from pancreatic surgery (20). Other techniques (i.e., rapid evaporative ionization MS and laser-based MS devices) have been developed for in vivo cancer detection (21–24). However, these techniques have not yet been demonstrated for pancreatic cancer tissue detection.We developed the MasSpec Pen system as a biocompatible handheld device coupled to a mass spectrometer for rapid (∼15 s) and nondestructive tissue analysis (25). Upon contact with a tissue and activation by a foot pedal, a discrete water droplet is formed and contained at the MasSpec Pen tip reservoir, allowing metabolites and lipids to be gently extracted into the water droplet, which is then transported to the mass spectrometer for analysis. To date, we have applied the MasSpec Pen in conjunction with least absolute shrinkage and selector operator (Lasso) penalized logistic regression to classify several tumor types ex vivo, achieving 96% overall accuracy in cross-validation (CV) (25–27). More recently, we translated the MasSpec Pen technology to an operating room (OR) to evaluate technical feasibility in open human surgeries and as a laparoscopic device in a robotic surgical procedure (28, 29).Here, we describe the application and first use of the MasSpec Pen for the acquisition and statistical prediction of molecular data acquired from pancreatic and biliary tissues, including in vivo data of surgical margins collected in an OR from patients undergoing pancreatic surgery. Collectively, our results indicate that the MasSpec Pen technology may be useful to enhance surgical margin evaluation in pancreatic cancer procedures by providing near–real-time diagnostic feedback to surgeons and physicians.     

Exploring the potential of a conditional cash transfer intervention to reduce HIV risk among young women in Iringa,Tanzania

Cash transfer programs seek to alter structural determinants of HIV risk such as poverty and gender inequality. We sought to explore the feasibility and potential effectiveness of a cash transfer intervention for young women as part of combination HIV prevention in Iringa, Tanzania. Qualitative, in-depth interviews were conducted with 116 stakeholders and residents from the region, including key informants, service delivery users, and members of key populations. Most respondents felt a cash transfer program would assist young women in Iringa to have more control over sexual decision-making and reduce poverty-driven transactional sex. Respondents were divided on who should receive funds: young women themselves, their parents/guardians, or community leaders. Cash amounts and suggested target groups varied, and several respondents suggested providing microcredit or small business capital instead of cash. Potential concerns included jealousy, dependency, and corruption. However, most respondents felt that some intervention was needed to address underlying poverty driving some sexual risk behavior. A cash transfer program could fill this role, ultimately reducing HIV, sexually transmitted infections, and unintended pregnancies. As increased attention is given to economic and structural interventions for HIV prevention, local input and knowledge should be considered in a program design.     

Location of the BCR/ABL Fusion Genes on Both Chromosomes 9 in Ph Negative Young CML Patients: An Indian Experience

The BCR/ABL gene rearrangement is cytogenetically visualized in most chronic myeloid leukemia (CML) cases. About 5–10 % of CML patients lack its cytogenetic evidence, however, shows BCR/ABL fusion by molecular methods. We describe two CML patients with Philadelphia (Ph) negative (−ve) and BCR/ABL positive by fluorescence in situ hybridization (FISH). Both the cases were in chronic phase at diagnosis. Conventional cytogenetics and different FISH assays were adopted using BCR/ABL probes. Home-brew FISH assay using bacterial artificial clone (BAC) for BAC-CTA/bk 299D3 for chromosomal region 22q13.31-q13.32 was performed in case 1. Both the patients were Ph-ve. In first case, dual color dual fusion (DCDF)-FISH studies revealed 1 Red (R) 2 Green (G) 1 Fusion (F) signal pattern in 80 % of cells indicating BCR/ABL fusion signals on chromosomes 9 instead of Ph and 2G2F signal pattern in 20 % of cells indicating two BCR/ABL fusions on both chromosomes 9q34 on presentation. In second case, FISH studies revealed the 1R1G1F signal pattern indicating BCR/ABL fusion signals on chromosomes 9 instead of Ph in 100 % of cells at presentation. During follow-up, both the patients exhibited 2G2F signal pattern indicating two BCR/ABL fusions on both chromosomes 9q34, which indicated a clonal evolution in 100 % cells. Both the patients did not achieve therapeutic response. Relocation of BCR/ABL fusion sequence on sites other than 22q11 represents a rare type of variant Ph, the present study highlights the hot spots involved in CML pathogenesis and signifies their implications in Ph−ve BCR/ABL positive CML. This study demonstrated the genetic heterogeneity of this subgroup of CML and strongly emphasized the role of metaphase FISH, especially in Ph−ve CML cases, as it detects variations of the classical t(9;22).     

Immune cell quantitation in normal breast tissue lobules with and without lobulitis

While the immune microenvironment has been investigated in breast cancers, little is known about its role in non-malignant breast tissues. Here we quantify and localize cellular immune components in normal breast tissue lobules, with and without visible immune infiltrates (lobulitis). Up to ten representative lobules each in eleven normal breast tissue samples were assessed for B cells (CD20), cytotoxic T cells (CD8), helper T cells (CD4), dendritic cells (CD11c), leukocytes (CD45), and monocytes/macrophages (CD68). Using digital image analysis, immune cell densities were measured and compared between lobules with/without lobulitis. 109 lobules in 11 normal breast tissue samples were evaluated; 31 with lobulitis and 78 without. Immune cells showed consistent patterns in all normal samples, predominantly localized to lobules rather than stroma. Regardless of lobulitis status, most lobules demonstrated CD8+, CD11c+, CD45+, and CD68+ cells, with lower densities of CD4+ and CD20+ cells. Both CD11c+ and CD8+ cells were consistently and intimately associated with the basal aspect of lobule epithelium. Significantly higher densities of CD4+, CD8+, CD20+, and CD45+ cells were observed in lobules with lobulitis. In contrast, densities of monocytes/macrophages and dendritic cells did not vary with lobulitis. In normal breast tissue, myeloid and lymphoid cells are present and localized to lobules, with cytotoxic T and dendritic cells directly integrated with epithelium. Lobules with lobulitis have significantly more adaptive immune (B and T) cells, but no increase in dendritic cells or monocytes/macrophages. These findings indicate an active and dynamic mucosal immune system in normal breast tissue.     

Pediatric Delirium: Evaluation,Management, and Special Considerations

Delirium describes a syndrome of acute brain dysfunction with severe consequences on patient outcomes, medical cost, morbidity, and mortality. It represents a final common pathway of numerous pathophysiologic disturbances disrupting cerebral homeostasis. The diagnosis is predicated on recognition of the clinical features of the syndrome through ongoing clinical assessment. Early identification can be aided by routine screening, particularly in high-risk populations. Evaluation and management are continuous and simultaneous processes involving a multidisciplinary care team including child psychiatry consultation. Prevention, early identification and management are critical in alleviating symptoms, improving outcomes, and reducing distress for patients, families, and care teams. This review highlights our current understanding regarding pediatric delirium, its mechanisms, clinical manifestations, detection and management.