Osteopathic Manipulative Treatment During Post-operative Recovery: A Scoping Review.

Surgery is a common and often necessary treatment option for a wide range of medical conditions, with an estimated 40 to 50 million surgeries performed in the US alone each year. While the various types of surgeries performed may be effective in treating or managing different conditions, the post-operative period can be challenging for patients. Osteopathic manipulative treatment (OMT) is a hands-on approach to medical care that seeks to restore balance and harmony to the body from the lens of an interconnected mind, body, and spirit. Given the potential for adverse events in patients following surgical treatments, OMT may be a viable adjunct post-operatively to enhance patient care and recovery. The purpose of this scoping review is to evaluate the state of current research examining the effectiveness of OMT in improving outcomes in post-operative patients. Three hundred articles were collected; 53 duplicates were removed. Eleven independent reviewers evaluated all 247 articles. Thirty articles were identified, including nine in general surgery, six in cardiothoracic surgery, five in orthopedic surgery, four in spinal surgery, three in neurosurgery, and three others (otolaryngology, oral/maxillofacial, and gynecologic surgery). Post-operative patients were treated with various OMT techniques with myofascial release and muscle energy being some of the most common treatments utilized in all surgical fields. Many studies demonstrated the benefits of OMT usage including significant pain relief, improved and earlier bowel function, and decreased lengths of hospital stay. This study demonstrates how OMT can be effective in reducing post-operative pain, reducing the incidence of post-operative ileus, and shortening the length of stay. Further research into the utilization of OMT in post-operative patients should be considered a potential adjunct to surgical intervention, especially in vulnerable patient populations.

Osteopathic Manipulative Treatment in Dysmenorrhea: A Systematic Review.

The majority of women experience dysmenorrhea during their lifetime. The current standard-of-care treatment consists of nonsteroidal anti-inflammatory drugs, oral contraceptive pills, or intrauterine devices. Osteopathic manipulative treatment (OMT) is a beneficial tool for improving non-musculoskeletal (non-MSK) conditions such as migraines, gastroesophageal reflux disease (GERD), and anxiety. OMT should be utilized to improve other non-MSK conditions, such as dysmenorrhea. The current review aims to evaluate the effects of OMT in women with dysmenorrhea. An extensive search was conducted in Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, Biomedical Reference Collection: Comprehensive, and Nursing & Allied Health Collection: Comprehensive from inception to June 2022. Studies evaluating the use of OMT in patients with dysmenorrhea were included, while editorial/opinion articles were excluded. Three independent reviewers evaluated the studies. Ten studies evaluating the use of OMT in patients with dysmenorrhea were included. Overall, OMT was shown to provide relief of symptoms, including back and menstrual pain; however, there was no guideline on which OMT techniques are the most successful. Numerous positive effects were found, including a reduction in the duration of pain, reduction of pain intensity, and reduction of analgesic use. However, the low number of studies supports the need for further investigations. Dysmenorrhea patients could benefit from a prospective randomized controlled trial targeting spinal facilitation and viscerosomatic reflexes to decrease pain duration, pain intensity, and analgesic use. Non-MSK-focused OMT has a large body of mostly anecdotal evidence for relief of conditions such as migraine, GERD, and anxiety. It has helped when traditional standards of care have failed. Non-MSK-focused OMT research represents a relatively untouched field of research that can have a profound and positive global impact, particularly in areas with poor income/healthcare access.

Non-steroidal Anti-inflammatory Drugs and Osteopathic Manipulative Treatment for Pain Management in Patients With Osteoarthritis: A Literature Review.

The pathophysiology of osteoarthritis (OA) involves the destruction of articular cartilage and the overgrowth of bone with lipping and spur formation. Nerve endings in the joint capsule and adjacent tissues play a major role in the pain mechanisms of osteoarthritis. This often requires patients to seek pain control measures beyond over-the-counter drugs, such as local anesthetics. Osteopathic manipulation treatment (OMT) is a conservative, non-pharmacological treatment that can be used to help treat chronic pain associated with OA. Other non-pharmacologic therapies include weight loss, exercise, physical therapy (PT), and assistive devices. However, pharmacologic management may be added synergistically to control flares and maintain baseline activities of daily living. While oral non-steroidal anti-inflammatory drugs (NSAIDs) have been the mainstay of treatment for pain and inflammation associated with OA, they have a non-selective inhibitory action that often results in negative side effects when used chronically. The possibility of minimizing these complications through alternate treatments such as topical NSAIDs provides an opportunity for patients to receive adequate pain relief from OA without suffering unnecessary consequences. This literature review seeks to assess the state of research regarding topical NSAIDs and OMT as alternatives to the current gold-standard treatment of OA. The significant inclusion criteria consisted of articles that described the effects of OMT on OA or the use of topical NSAIDs such as Voltaren on OA. Due to the limited articles found, a qualitative analysis was performed, and the salient conclusions are outlined. Alternative pharmacological and non-pharmacological treatments, such as topical diclofenac gel and OMT, have shown promising results in the treatment of pain in OA. It is seen that a majority of patients achieve pain management using NSAIDs, acetaminophen, or topical analgesics. Both diclofenac sodium and OMT have individually been shown to be effective treatments of OA when compared to the use of oral NSAIDs. A holistic treatment approach that utilizes both topical diclofenac sodium and OMT may provide OA patients with an effective option to reduce their moderate to severe chronic pain with limited side effects. Further, high-quality randomized controlled trials are needed to identify whether synergistic effects occur when combining diclofenac sodium gel and OMT for pain relief in patients with OA.

Tracing geochemical sources and health risk assessment of uranium in groundwater of arid zone of India.

Water quality degradation and metal contamination in groundwater are serious concerns in an arid region with scanty water resources. This study aimed at evaluating the source of uranium (U) and potential health risk assessment in groundwater of the arid region of western Rajasthan and northern Gujarat. The probable source of vanadium (V) and fluorine (F) was also identified. U and trace metal concentration, along with physicochemical characteristics were determined for 265 groundwater samples collected from groundwater of duricrusts and palaeochannels of western Rajasthan and northern Gujarat. The U concentration ranged between 0.6 and 260 µg L-1 with a mean value of 24 µg L-1, and 30% of samples surpassed the World Health Organization's limit for U (30 µg L-1). Speciation results suggested that dissolution of primary U mineral, carnotite [K2(UO2)2(VO4)2·3H2O] governs the enrichment. Water-rock interaction and evaporation are found the major hydrogeochemical processes controlling U mineralization. Groundwater zones having high U concentrations are characterized by Na-Cl hydrogeochemical facies and high total dissolved solids. It is inferred from geochemical modelling and principal component analysis that silicate weathering, bicarbonate complexation, carnotite dissolution, and ion exchange are principal factors controlling major solute ion chemistry. The annual ingestion doses of U for all the age groups are found to be safe and below the permissible limit in all samples. The health risk assessment with trace elements manifested high carcinogenic risks for children.

New developments in existing WHO entities and evolving molecular concepts: The Genitourinary Pathology Society (GUPS) update on renal neoplasia.

The Genitourinary Pathology Society (GUPS) reviewed recent advances in renal neoplasia, particularly post-2016 World Health Organization (WHO) classification, to provide an update on existing entities, including diagnostic criteria, molecular correlates, and updated nomenclature. Key prognostic features for clear cell renal cell carcinoma (RCC) remain WHO/ISUP grade, AJCC/pTNM stage, coagulative necrosis, and rhabdoid and sarcomatoid differentiation. Accrual of subclonal genetic alterations in clear cell RCC including SETD2, PBRM1, BAP1, loss of chromosome 14q and 9p are associated with variable prognosis, patterns of metastasis, and vulnerability to therapies. Recent National Comprehensive Cancer Network (NCCN) guidelines increasingly adopt immunotherapeutic agents in advanced RCC, including RCC with rhabdoid and sarcomatoid changes. Papillary RCC subtyping is no longer recommended, as WHO/ISUP grade and tumor architecture better predict outcome. New papillary RCC variants/patterns include biphasic, solid, Warthin-like, and papillary renal neoplasm with reverse polarity. For tumors with 'borderline' features between oncocytoma and chromophobe RCC, a term "oncocytic renal neoplasm of low malignant potential, not further classified" is proposed. Clear cell papillary RCC may warrant reclassification as a tumor of low malignant potential. Tubulocystic RCC should only be diagnosed when morphologically pure. MiTF family translocation RCCs exhibit varied morphologic patterns and fusion partners. TFEB-amplified RCC occurs in older patients and is associated with more aggressive behavior. Acquired cystic disease (ACD) RCC-like cysts are likely precursors of ACD-RCC. The diagnosis of renal medullary carcinoma requires a negative SMARCB1 (INI-1) expression and sickle cell trait/disease. Mucinous tubular and spindle cell carcinoma (MTSCC) can be distinguished from papillary RCC with overlapping morphology by losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22. MTSCC with adverse histologic features shows frequent CDKN2A/2B (9p) deletions. BRAF mutations unify the metanephric family of tumors. The term "fumarate hydratase deficient RCC" ("FH-deficient RCC") is preferred over "hereditary leiomyomatosis and RCC syndrome-associated RCC". A low threshold for FH, 2SC, and SDHB immunohistochemistry is recommended in difficult to classify RCCs, particularly those with eosinophilic morphology, occurring in younger patients. Current evidence does not support existence of a unique tumor subtype occurring after chemotherapy/radiation in early childhood.

Development and Validation of a Clinical Prognostic Stage Group System for Nonmetastatic Prostate Cancer Using Disease-Specific Mortality Results From the International Staging Collaboration for Cancer of the Prostate.

Importance: In 2016, the American Joint Committee on Cancer (AJCC) established criteria to evaluate prediction models for staging. No localized prostate cancer models were endorsed by the Precision Medicine Core committee, and 8th edition staging was based on expert consensus. Objective: To develop and validate a pretreatment clinical prognostic stage group system for nonmetastatic prostate cancer. Design, Setting, and Participants: This multinational cohort study included 7 centers from the United States, Canada, and Europe, the Shared Equal Access Regional Cancer Hospital (SEARCH) Veterans Affairs Medical Centers collaborative (5 centers), and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (43 centers) (the STAR-CAP cohort). Patients with cT1-4N0-1M0 prostate adenocarcinoma treated from January 1, 1992, to December 31, 2013 (follow-up completed December 31, 2017). The STAR-CAP cohort was randomly divided into training and validation data sets; statisticians were blinded to the validation data until the model was locked. A Surveillance, Epidemiology, and End Results (SEER) cohort was used as a second validation set. Analysis was performed from January 1, 2018, to November 30, 2019. Exposures: Curative intent radical prostatectomy (RP) or radiotherapy with or without androgen deprivation therapy. Main Outcomes and Measures: Prostate cancer-specific mortality (PCSM). Based on a competing-risk regression model, a points-based Score staging system was developed. Model discrimination (C index), calibration, and overall performance were assessed in the validation cohorts. Results: Of 19 684 patients included in the analysis (median age, 64.0 [interquartile range (IQR), 59.0-70.0] years), 12 421 were treated with RP and 7263 with radiotherapy. Median follow-up was 71.8 (IQR, 34.3-124.3) months; 4078 (20.7%) were followed up for at least 10 years. Age, T category, N category, Gleason grade, pretreatment serum prostate-specific antigen level, and the percentage of positive core biopsy results among biopsies performed were included as variables. In the validation set, predicted 10-year PCSM for the 9 Score groups ranged from 0.3% to 40.0%. The 10-year C index (0.796; 95% CI, 0.760-0.828) exceeded that of the AJCC 8th edition (0.757; 95% CI, 0.719-0.792), which was improved across age, race, and treatment modality and within the SEER validation cohort. The Score system performed similarly to individualized random survival forest and interaction models and outperformed National Comprehensive Cancer Network (NCCN) and Cancer of the Prostate Risk Assessment (CAPRA) risk grouping 3- and 4-tier classification systems (10-year C index for NCCN 3-tier, 0.729; for NCCN 4-tier, 0.746; for Score, 0.794) as well as CAPRA (10-year C index for CAPRA, 0.760; for Score, 0.782). Conclusions and Relevance: Using a large, diverse international cohort treated with standard curative treatment options, a proposed AJCC-compliant clinical prognostic stage group system for prostate cancer has been developed. This system may allow consistency of reporting and interpretation of results and clinical trial design.

Radiological and pollution risk assessments of terrestrial radionuclides and heavy metals in a mineralized zone of the siwalik region (India).

The present study reveals the distribution of terrestrial radionuclides (226Ra, 232Th and 40K) and heavy metals (Cr, Ni, Cu, Zn, Pb, Co) from soil samples of Una, Hamirpur and Kangra districts of Himachal Pradesh (India). The 226Ra, 232Th, 40K activity concentration in the studied region has been varied from 8 to 3593 Bq kg-1; 21-370 Bq kg-116; 62-7130 Bq kg-1 respectively. High disequilibrium factor (238U/226Ra) depicts that uranium constantly migrates from clay oxidizing zone and getting precipitated with enrichment towards south. An attempt has been made to correlate the distribution of these radionuclides and heavy metals with geology and rock type formation of Siwalik region. The concentration of Pb, Zn and Co was found higher than Indian average background value. Multiple radiological and pollution indices have been estimated for proper risk analysis in the studied region. The annual effective dose in studied region is lower than the recommended limit of 1.0 mSv a-1. The obtained geo-accumulation index and enrichment factor indicated that the sites located in the Hamirpur and Kangra regions were moderately contaminated with Pb and Co. The Nemerow pollution index and contamination security index suggested that almost 45% sites were slightly to moderately polluted. The non-carcinogenic and carcinogenic risks for both children and adults were within acceptable limits.

Performance of clinicopathologic models in men with high risk localized prostate cancer: impact of a 22-gene genomic classifier.

BACKGROUND: Prostate cancer exhibits biological and clinical heterogeneity even within established clinico-pathologic risk groups. The Decipher genomic classifier (GC) is a validated method to further risk-stratify disease in patients with prostate cancer, but its performance solely within National Comprehensive Cancer Network (NCCN) high-risk disease has not been undertaken to date. METHODS: A multi-institutional retrospective study of 405 men with high-risk prostate cancer who underwent primary treatment with radical prostatectomy (RP) or radiation therapy (RT) with androgen-deprivation therapy (ADT) at 11 centers from 1995 to 2005 was performed. Cox proportional hazards models were used to determine the hazard ratios (HR) for the development of metastatic disease based on clinico-pathologic variables, risk groups, and GC score. The area under the receiver operating characteristic curve (AUC) was determined for regression models without and with the GC score. RESULTS: Over a median follow-up of 82 months, 104 patients (26%) developed metastatic disease. On univariable analysis, increasing GC score was significantly associated with metastatic disease ([HR]: 1.34 per 0.1 unit increase, 95% confidence interval [CI]: 1.19-1.50, p < 0.001), while age, serum PSA, biopsy GG, and clinical T-stage were not (all p > 0.05). On multivariable analysis, GC score (HR: 1.33 per 0.1 unit increase, 95% CI: 1.19-1.48, p < 0.001) and GC high-risk (vs low-risk, HR: 2.95, 95% CI: 1.79-4.87, p < 0.001) were significantly associated with metastasis. The addition of GC score to regression models based on NCCN risk group improved model AUC from 0.46 to 0.67, and CAPRA from 0.59 to 0.71. CONCLUSIONS: Among men with high-risk prostate cancer, conventional clinico-pathologic data had poor discrimination to risk stratify development of metastatic disease. GC score was a significant and independent predictor of metastasis and may help identify men best suited for treatment intensification/de-escalation.

INGESTION AND INHALATION DOSES DUE TO INTAKE OF RADON IN DRINKING WATER SAMPLES OF AMRITSAR PROVINCE, PUNJAB, INDIA.

In the present investigation, the ingestion and inhalation dosage for the particular body organs in light of the intake of radon through ground water utilised by the occupants have been assessed in the different villages of the Upper Bari Doab region of Amritsar province, India using an electrostatic collection type radon monitor (RAD7) analyzer with RAD-H2O accessory. The mean radon activity level in water was seen to be 8.34 ± 2.99 Bql-1. The newborn children have higher radiation dosage than the other age groups because of their high dosage transformation factors. However, the radiation dosage received by all different age groups significantly less than the UNSCEAR and WHO suggested a level of 100 µSv y-1. The annual effective dosage for the diverse body organs because of the intake of radon was moreover ascertained and found the maximum dosage for lungs than other organs. The radiation dosage received by bronchial epithelium by the means of inhalation was likewise high when contrasted with that by stomach walls through ingestion.

Age-dependent ingestion and inhalation doses due to intake of uranium and radon in water samples of Shiwalik Himalayas of Jammu and Kashmir, India.

The research work involved the ingestion and inhalation doses due to the intake of radon and uranium through water samples used by the inhabitants, measured in the villages of the Shiwalik Himalayas of Jammu and Kashmir, India. The uranium concentration in collected water samples was assessed by LED fluorimetric technique. All values of doses were found to be below the proposed limit of 100 µSv year-1 for all age categories except for infants due to the high-dose conversion factor. The annual effective doses for the various body organs due to the intake of radon was also calculated and found the maximum dose for lungs than other organs. The concentration of radon in water samples was assessed by Smart Rn Duo portable monitor and compared with RAD7. Statistical analysis was carried out and the Shapiro and Wilk (Biometrika, 52(3/4), 591-611, 1965) test has been also used for the distribution of the data. The physicochemical parameters were also measured in the collected water samples.

Toxicological risk assessment of protracted ingestion of uranium in groundwater.

Groundwater samples have been collected from far-reaching locations in Solan and Shimla districts of Himachal Pradesh, India, and studied for uranium concentration using LED fluorimetry. In this region, uranium in groundwater varies from 0.12 to 19.43 µg L-1. Radiological and chemical toxicity is accounted for different uranium isotopes. The average mortality risk for uranium isotopes 234U, 235U, and 238U are 2.6 × 10-12, 3.5 × 10-10, and 5.9 × 10-8, respectively. Similarly, the mean morbidity risk for 234U, 235U and 238U are 4.1 × 10-12, 5.6 × 10-10 and 9.5 × 10-8, respectively. An attempt has also been made to calculate doses for different age-groups. Highest doses, ranging from 0.30 to 48.23 µSv year-1, are imparted to infants of 7-12 months of age which makes them the most vulnerable group of population. Using Hair Compartmental Model for uranium and mean daily uranium intake of 3.406 µg for 60-year exposure period, organ-specific doses due to uranium radioisotopes, retention in prime organs/tissues and excretion rates via urine, feces and hair pathway are estimated. In this manuscript, the transfer coefficients for kidney, liver, skeleton, GI tract, soft tissues, urinary bladder, and blood are analyzed. Hair compartment model and ICRP's biokinetic model are compared in terms of uranium load in different organs after 60 years of protracted ingestion. The study on biokinetic behavior of uranium is the first of its kind in the area which is dedicated to environmental and social cause.

Risk estimation and multivariate statistical analysis of the heavy metal content of drinking water samples.

Drinking water samples of Jaipur and Ajmer districts of Rajasthan, India, were collected and analyzed for the measurement of concentration of heavy metals. The purpose of this study was to determine the sources of the heavy metals in the drinking water. Inductively coupled plasma mass spectrometry was used for the determination of the heavy metal concentrations, and for the statistical analysis of the data, principal component analysis and cluster analysis were performed. It was observed from the results that with respect to WHO guidelines, the water samples of some locations exceeded the contamination levels for lead (Pb), selenium (Se), and mercury (Hg), and with reference to the EPA guidelines, the samples were determined unsuitable for drinking because of high concentrations of Pb and Hg. Using multivariate statistical analysis, we determined that copper, manganese, arsenic, Se, and Hg were of anthropogenic origin, while Pb, copper, and cadmium were of geogenic origin. The present study reports the dominance of the anthropogenic contributions over geogenics in the studied area. The sources of the anthropogenic contaminants need to be investigated in a future study.

Development and Validation of a Novel Integrated Clinical-Genomic Risk Group Classification for Localized Prostate Cancer.

Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses. Competing risks analysis was used to estimate the risk of distant metastasis. Time-dependent c-indices were constructed to compare clinicopathologic risk models with the clinical-genomic risk groups. Results With a median follow-up of 8 years for patients in the training cohort, 10-year distant metastasis rates for National Comprehensive Cancer Network (NCCN) low, favorable-intermediate, unfavorable-intermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the three-tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%, 29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively, which were consistent in the validation cohort (0%, 25.9%, and 55.2%, respectively). C-indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61 to 0.93) were improved over NCCN (0.73; 95% CI, 0.60 to 0.86) and Cancer of the Prostate Risk Assessment (0.74; 95% CI, 0.65 to 0.84), and 30% of patients using NCCN low/intermediate/high would be reclassified by the new three-tier system and 67% of patients would be reclassified from NCCN six-tier (very-low- to very-high-risk) by the new six-tier system. Conclusion A commercially available genomic classifier in combination with standard clinicopathologic variables can generate a simple-to-use clinical-genomic risk grouping that more accurately identifies patients at low, intermediate, and high risk for metastasis and can be easily incorporated into current guidelines to better risk-stratify patients.

Exposure assessment of natural uranium from drinking water.

The uranium concentration in the drinking water of the residents of the Jaipur and Ajmer districts of Rajasthan has been measured for exposure assessment. The daily intake of uranium from the drinking water for the residents of the study area is found to vary from 0.4 to 123.9 µg per day. For the average uranium ingestion rate of 35.2 µg per day for a long term exposure period of 60 years, estimations have been made for the retention of uranium in different body organs and its excretion with time using ICRP's biokinetic model of uranium. Radioactive and chemical toxicity of uranium has been reported and discussed in detail in the present manuscript.

Standardizing the definition of adverse pathology for lower risk men undergoing radical prostatectomy.

PURPOSE: Numerous definitions of adverse pathology at radical prostatectomy (RP) have been proposed and implemented for both research and clinical care, and there is tremendous variation in the specific criteria used to define adverse pathology in these settings. Given the current landscape in which magnetic resonance imaging criteria and biomarker cutoffs are validated for disparate adverse pathology definitions, we sought to identify which of these is most closely tied to biochemical recurrence (BCR) after RP. MATERIALS AND METHODS: A total of 2,837 patients who underwent RP at a single institution for localized prostate cancer (PCa) were included. We evaluated the following existing definitions of adverse pathology at RP: (1) Gleason score ≥7, (2) primary Gleason pattern ≥4, (3) Gleason score ≥7 or pathologic stage T3-4, (4) pathologic stage T3-4, (5) primary Gleason pattern ≥4 or pathologic stage T3-4. The primary outcome measure was BCR. Multiple statistical techniques were used to assess BCR prediction. RESULTS: Of the 5 definitions assessed, 1 (primary Gleason pattern ≥4 or pathologic stage T3-4, 540 patients [19% of cohort]) consistently outperformed the other definitions across all statistical measures. Additionally, a total of only 13 (6.6%) and 34 (10.3%) men with very-low-risk and low-risk cancer per National Comprehensive Cancer Network guideline, respectively, met this definition of adverse pathology at the time of RP. CONCLUSIONS: Varying definitions of adverse pathology differ in their prognostic performance. The criteria defined by either primary Gleason pattern ≥4 or pT3-4 disease appears to most accurately predict BCR in this subset of patients with lower risk PCa at the time of diagnosis. Additionally, men with very-low-risk or low-risk PCa per National Comprehensive Cancer Network guidelines are relatively unlikely to have adverse pathology at the time of surgical resection. These data may help inform the use of imaging and molecular markers as well as the intensity of surveillance in men with newly diagnosed PCa.

Targeted mutagenesis of zebrafish antithrombin III triggers disseminated intravascular coagulation and thrombosis, revealing insight into function.

Pathologic blood clotting is a leading cause of morbidity and mortality in the developed world, underlying deep vein thrombosis, myocardial infarction, and stroke. Genetic predisposition to thrombosis is still poorly understood, and we hypothesize that there are many additional risk alleles and modifying factors remaining to be discovered. Mammalian models have contributed to our understanding of thrombosis, but are low throughput and costly. We have turned to the zebrafish, a tool for high-throughput genetic analysis. Using zinc finger nucleases, we show that disruption of the zebrafish antithrombin III (at3) locus results in spontaneous venous thrombosis in larvae. Although homozygous mutants survive into early adulthood, they eventually succumb to massive intracardiac thrombosis. Characterization of null fish revealed disseminated intravascular coagulation in larvae secondary to unopposed thrombin activity and fibrinogen consumption, which could be rescued by both human and zebrafish at3 complementary DNAs. Mutation of the human AT3-reactive center loop abolished the ability to rescue, but the heparin-binding site was dispensable. These results demonstrate overall conservation of AT3 function in zebrafish, but reveal developmental variances in the ability to tolerate excessive clot formation. The accessibility of early zebrafish development will provide unique methods for dissection of the underlying mechanisms of thrombosis.

Analysis of uranium concentration in drinking water samples using ICPMS.

Uranium concentration in drinking water samples collected from some areas of Northern Rajasthan has been measured using inductively coupled plasma mass spectrometry. The water samples were taken from hand pumps. The uranium concentration in water samples varies from 2.54-133.0 µg L with a mean value of 38.48 µg L. The uranium concentration in most of the drinking water samples exceeds the safe limit (30 µg L) recommended by the World Health Organization. The annual effective dose associated with drinking water due to uranium concentration is estimated from its annual intake using dosimetric information based on ICRP 72. The resulting value of the annual effective dose from drinking water sources is in the range of 2.11-110.45 µSv. The annual effective dose in one of the samples was found to be greater than WHO-recommended level of 100 µSv y.

Uranium, radium and radon exhalation studies in geological samples belonging to some areas of punjab, using track etching technique.

With a view to prospect the uranium, radium and radon concentration and related health risk assessments in areas of Muktsar and Ferozepur districts in Punjab, the fission track registration technique has been used for the analysis of water and soil samples. Uranium content in water ranged from 5.47 to 10.19 microg/l(-1) and 6.28 to 11.74 microg/l(-1) for Muktsar and Ferozepur respectively. Uranium content in soil samples of Muktsar and Ferozepur ranged from 1.14 to 1.90 mg/kg(-1) and 1.26 to 2.44 mg/kg(-1) respectively. Radium concentration in these soil samples has been found to vary from 3.97 to 15.94 bq/kg(-1) and 7.24 to 24.14 bq/kg(-1) for Muktsar and Ferozepur respectively. The radon exhalation values were calculated in terms of area (E(A)) and mass (E(M)). The values of E(M) ranged from 4.9 to 20.6 (mbqkg(-1) hr(-1)) for Muktsar and 9.4 to 31.3 (mbqkg(-1)hr(-1)) for Ferozepur and values of E(A) ranged from 173 to 728 (mbqm(-2)hr(-1)) for Muktsar and 330 to 1102 (mbqm(-2)hr(-1)) for Ferozepur district. These values in general are low and not significant from health hazard point of view. The values of uranium concentration in water samples of these areas are lower than those reported for soil and water samples of Himachal Pradesh. These values are also lower than those reported by Singh et al. for the rocks belonging to uranium and copper mines of Bihar.