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Using a Sendai Virus based vector delivering Yamanaka Factors, we generated induced Pluripotent Stem Cells (iPSCs) from peripheral blood mononuclear cells of a patient affected by Ataxia Telangiectasia (AT), caused by a novel homozygous deletion in ATM, spanning exons 5-7. Three clones were fully characterized for pluripotency and capability to differentiate. These clones preserved the causative mutation of parental cells and genomic stability over time (>100 passages). Furthermore, in AT derived iPSCs we confirmed the impaired DNA damage response after ionizing radiation. All these data underline potential usefulness of our clones as in vitro AT disease model.

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The new Version 2.3 of the GPCP Monthly analysis is described in terms of changes made to improve the homogeneity of the product, especially after 2002. These changes include corrections to cross calibration of satellite data inputs and updates to the gauge analysis. Over ocean, changes starting in 2003 result in an overall precipitation increase of 1.8% after 2009. Updating the gauge analysis to its final, high quality version increases the global land total by 1.8% for the post-2002 period. These changes correct a small, incorrect dip in the estimated global precipitation over the last decade in the earlier Version 2.2. The GPCP analysis is also used to describe global precipitation for 2017. The general La Nina pattern for 2017 is noted and the evolution from the early 2016 El Nino pattern is described. The 2017 global value is one of the highest for the 19792017 period, exceeded only by 2016 and 1998 (both El Nino years) and reinforces the small positive trend. Results for 2017 also reinforce significant trends in precipitation intensity (on a monthly scale) in the tropics. These results for 2017 indicate the value of the GPCP analysis for climate monitoring in addition to research.

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The International Precipitation Working Group (IPWG) is a permanent International Science Working Group (ISWG) of the Coordination Group for Meteorological Satellites (CGMS), co-sponsored by CGMS and the World Meteorological Organization (WMO). The IPWG provides a focal point and forum for the international scientific community to address the issues and challenges of satellite-based quantitative precipitation retrievals, and for the operational agencies to access and make use of precipitation products. Through partnerships and biennial meetings, the group supports the exchange of information on techniques for retrieving and measuring precipitation and for enhancing the impact of space-borne precipitation retrievals in numerical weather and hydrometeorological prediction and climate studies. The group furthers the refinement of current estimation techniques and the development of new methodologies for improved global precipitation measurements, together with the validation of the derived precipitation products with ground-based precipitation measurements. The IPWG identifies critical issues, provides recommendations to the CGMS and supports upcoming precipitation-oriented missions. Training activities on precipitation retrieval from space are also part of the IPWG mandate in cooperation with WMO and other bodies.

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The Earth System Prediction Suite (ESPS) is a collection of flagship U.S. weather and climate models and model components that are being instrumented to conform to interoperability conventions, documented to follow metadata standards, and made available either under open source terms or to credentialed users. The ESPS represents a culmination of efforts to create a common Earth system model architecture, and the advent of increasingly coordinated model development activities in the U.S. ESPS component interfaces are based on the Earth System Modeling Framework (ESMF), community-developed software for building and coupling models, and the National Unified Operational Prediction Capability (NUOPC) Layer, a set of ESMF-based component templates and interoperability conventions. This shared infrastructure simplifies the process of model coupling by guaranteeing that components conform to a set of technical and semantic behaviors. The ESPS encourages distributed, multi-agency development of coupled modeling systems, controlled experimentation and testing, and exploration of novel model configurations, such as those motivated by research involving managed and interactive ensembles. ESPS codes include the Navy Global Environmental Model (NavGEM), HYbrid Coordinate Ocean Model (HYCOM), and Coupled Ocean Atmosphere Mesoscale Prediction System (COAMPS®); the NOAA Environmental Modeling System (NEMS) and the Modular Ocean Model (MOM); the Community Earth System Model (CESM); and the NASA ModelE climate model and GEOS-5 atmospheric general circulation model.

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Thyroid diseases may be related to gastrointestinal motility symptoms. Such symptoms can vary in degree and, sometimes, are the only clue of a thyroid disease or, at least, the first. The mechanism by which the thyroid hormones can influence gastrointestinal motility, even if not still completely elucidated, can be found in a synergism between a direct effect of the thyronins and an indirect effect mediated by cathecolamines on the muscle cell receptors. Neck discomfort and dysphagia are common findings in patients with thyroid diseases. Hyper- and hypothyroidism can impair esophageal motility, modifying pharyngo-esophageal structure and/or muscular function and interacting with the neuro-humoral regulation of the esophageal peristalsis. Oesophageal motility alterations, observed in patients affected by small non-toxic goiter, are less understandable. At the gastro-duodenal level, basic and postprandial electric rhythm alterations have been observed in hyperthyroid patients, often associated with delayed gastric emptying, too. In such patients, the autonomous nervous system dysfunction may even modify the neuro-hormonal mutual regulation (vagal influence decrease) of the gastro-duodenal myoelectric activity. Hypothyroidism may cause a delay of the gastric emptying too, but such pattern may also be related to an associated autoimmune disease or to an independent chronic modification of the gastric mucosa. Diarrhoea and malabsorption are common findings together with hyperthyroidism, whereas constipation is frequently observed in hypothyroidism. The clinically most demanding situation is certainly the secondary chronic intestinal pseudo-obstruction syndrome, which involves the bowel in most cases, but may also show up by means of a mega-small bowel or a mega-duodenum, or even all of the above. In conclusion it may be stated that: 1) thyroid diseases may be related to symptoms due to digestive motility dysfunction. 2) Any segment of the gastrointestinal trait may be involved. 3) The typical clinical manifestations of the thyroid illnesses may be borderline, missing or concealed by other intercurrent illnesses, especially in the elderly patients. 4) Motility-related digestive symptoms may conceal an underlying, easily misdetected, thyroid disease and must be therefore carefully analyzed.

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BACKGROUND: This is a retrospective review of medical and financial records to test the hypothesis that the use of a critical pathway specifically designed for the management of laryngectomy patients will result in improved patient care, decreased length of hospitalization, and optimal allocation of resources. METHODS: Thirty patients undergoing laryngectomy before the implementation of the laryngectomy critical pathway were compared with 30 patients after implementation of the pathway. Clinical outcomes, length of hospitalization, and cost analyses were performed. RESULTS: Adjusting for two outliers, the average length of stay for pathway patients was 7.3 days vs 12 days for prepathway patients. A total estimated cost-savings of $204,000 was ultimately achieved. CONCLUSIONS: Our laryngectomy critical pathway has resulted in improved patient care and optimized allocation of medical resources.

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OBJECTIVE: Recent reports have suggested improvement in the last decade in global outcome measures after subarachnoid hemorrhage (SAH), particularly in patients presenting in good initial neurological status. We used a standardized self-report instrument, the Reintegration to Normal Living (RNL) Index, to assess a patient-based quality of life measure and a self-report of work status. We tested the hypothesis that several patient-based factors were related to these outcomes, including depressive symptoms, physical disability, age, and initial Hunt and Hess grade. Using these data, we report the total management morbidity and mortality at 1 to 5 years after SAH for patients initially presenting in good neurological condition. METHODS: The study population consisted of 246 consecutive patients admitted to our tertiary care center with aneurysmal SAH in good neurological condition (Hunt and Hess Grades I-III). Patients underwent either surgical (92%), endovascular (7%), or medical (1 %) management of aneurysmal SAH. Eighty-three percent of surviving patients completed a written or telephone questionnaire incorporating the Barthel Index, the Zung Self-rating Depression Scale, the RNL Index, and a work status assessment. RESULTS: An aneurysm-related mortality rate of 6% was observed in the patient population. Fifty-five percent of patients reported a complete reintegration into their normal living situation, as measured by the RNL Index. Sixty-seven percent of previously full-time workers returned to a full-time status. Thirty-six percent of patients reported depressive symptoms, and 23% of patients reported physical disability. In a multivariate model, the two factors that contributed most to an impairment of reintegration were depression and physical disability, whereas a failure to return to work was related to older age and a higher-grade initial neurological status. CONCLUSION: In this series of patients undergoing multimodality management of lower-grade SAH, more than one-half of patients subsequently reported a normal reintegration into their social situation, as assessed by the RNL Index. Standardized assessments of cofactors associated with impaired reintegration revealed that depressive symptoms and physical disability played a strong role in overall reintegration. Standardized assessments, such as the RNL Index, offer the potential for improved comparison of different treatment regimens and specific therapeutic targeting of factors, such as depression, which contribute to decreased quality of life.

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OBJECTIVE: The goal was to compare complication rates and recovery times in patients undergoing elective septoplasty or endoscopic sinus surgery using local anesthesia with sedation (LAS) versus general anesthesia (GA). METHODS AND PATIENTS: A retrospective chart review of a consecutive sample of 177 patients undergoing elective septoplasty or endoscopic sinus surgery between July 1, 1994, and June 30, 1996, was carried out at our university-based outpatient surgery unit. Outcome measures included total operative time, surgical time, recovery time, and perioperative complications. RESULTS: Total operative and recovery times were shorter in patients undergoing LAS. The frequency of emesis, epistaxis, and nausea were less in the LAS population than in the GA population. Three patients who underwent GA required unplanned admissions. CONCLUSION: This study suggests that in selected patients undergoing sinonasal surgery, LAS may result in shorter total operative times, shorter recovery times, and less frequent nausea, emesis, and epistaxis than GA.

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Lower eyelid dysfunction in the patient with facial paralysis is frequently the result of several deleterious factors, including the loss of orbicularis tone, involutional changes in the canthal ligaments, the effect of aging on the midfacial soft tissue structures, and malposition of the lower eyelid punctum. This dysfunction is manifested as lagophthalmos, ectropion, and epiphora. Fortunately, there are several surgical methods by which the various abnormalities can be corrected or compensated for. This article addresses the management of the lower eyelid and several of the current methods available to the surgeon for management of the lower eyelid in facial paralysis.

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BACKGROUND: Further advances in endoscope technology have allowed the development of a new generation of tightly packed fiberoptics encased within a rigid ureteroscope. The tips of these semirigid ureteroscopes measure between 5.0F and 11.9F, and their working channels measure between 1.8F and 5.5F, which allows passage of routine endoscopc instruments. Additionally, several manufacturers have recently produced straight-channel fiberoptic semirigid endoscopes with an offset lens which allow usage of rigid lithotripsy devices. New fiber-packing techniques provide numerous pixels within the image bundle. These ureteroscopes have varied distal lens systems, but all have excellent vision in the field of view. METHODS: Over the past 28 months, we have performed transurethral ureteroscopy in 187 patients, having utilized semirigid ureteroscopes in 158 patients for diagnostic procedures (8.7 %), stone manipulation (78.7 %), removal of migrated stents (4.4%), and surgery of stricture, tumor, or foreign bodies (8.2%). In more than 50% of our cases, ureteral dilation was not necessary, and the semirigid ureteroscope was passed to the area of interest without difficulty. RESULTS: We accessed the site of pathology in 96.2% of patients. Overall, complications occurred in 6.9% of patients. However, of these problems, 93.6% were small ureteral perforations (only three of which were caused by the semirigid ureteroscope itself), and all cases but one were managed successfully by a ureteral stent. No postoperative strictures were noted. CONCLUSION: This new generation of semirigid fiberoptic ureteroscopes represents another significant advance in the endourologic management of ureteral disease.

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To determine the relation between high-energy shockwaves (HESW) and the presence of lipid peroxidation produces, juvenile pigs were subjected to shockwave lithotripsy (SWL). After lithotripsy, both treated and control kidneys were analyzed, along with urine samples collected before, during, and after SWL. Thiobarbituric acid-reactive substance (TBARS) and lipid-conjugated diene (CD) concentrations, used as markers for membrane lipid peroxidation, were determined in the kidney and urine samples. Significantly increased mean TBARS concentrations (146%) were associated with homogenates of lithotripsy-treated kidneys, 77.8 +/- 14.4 (SD) mmol/g v the controls, 31.4 +/- 14.9 mmol/g. Lithotripsy induction of lipid peroxidation products in the cortex, the gross damage site, and the respective medulla were also examined. In HESW-treated cortex samples, increased TBARS concentrations were seen--75.0 +/- 21.3 mmol/g--compared with untreated controls-- 45.2+/- 5.6 mmol/g--while increased CD concentrations (168%) were observed in the medulla of HESW-treated samples. No significant differences were observed in TBARS or CD concentrations in urine samples from control or treated kidneys, yet specific lipid hydroperperoxides were detected in the urine of HESW-treated kidneys. We conclude that HESW lithotripsy of swine kidneys is associated with increased lipid peroxidation products that may cause further cellular damage. Lipid peroxidation induced by SWL may be one of several mechanisms that lead to other potential bioeffects. Finally, analysis of specific lipid hydroperoxides in the urine of HESW-treated kidneys may serve as a noninvasive marker of renal injury after clinical SWL.

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Cocaine facilitates neurotransmitter release from the central nervous system, decreases their re-uptake at the synapse junction level and increases their blood level due to receptors blockade. During pregnancy cocaine inhibits uterine adrenergic beta receptors and easily crosses the placenta, the main obstetrical consequences of overstimulation of the noradrenergic system being miscarriage, retroplacental haematoma, ruptured uterus, short and premature labour. Fetal and neonatal consequences resulting from both a decreased uterine blood flow and a direct effect of cocaine on fetal development can be severe. Decreased uterine blood flow lowers oxygen and nutriment transport which in turn can induce intra-uterine growth retardation. The direct effect of cocaine on the fetus is responsible for an increased catecholamine plasma concentration leading to vasoconstriction episodes, increased heart rate and blood pressure, and subsequent oxygen requirement. Several malformations have been reported, sometimes severe (involving central nervous system, heart, digestive tract, urinary tract and bone) that are mainly due to fetal circulation failure. Cocaine can also directly alter brain development because of neuronal mistargeting within the cerebral cortex.

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We compared three independent techniques for measurement of total energy expenditure (TEE) in human subjects: 1) weight-maintaining energy intake (dietTEE), 2) 24-h chamber calorimetry (chamberTEE), and 3) differential elimination rates 2H2O and H(2)18O (isotopeTEE). Twenty-three healthy adult in-patients [19 never obese (NO), 2 obese (OB), and 2 formerly-obese (RO); 9 female, 14 malel] ingested a liquid formula diet (40% of calories as fat, 45% carbohydrate, 15% protein), the volume of which was adjusted until body weight was stable for at least 14 days. Body composition was then determined by hydrodensitometry, isotope dilution, and dual photon beam absorptiometry (DXA). The thermic effect of feeding (TEF) and resting energy expenditure [REE; measured before arising (dietREE) and after arising (chamberREE)] were determined by indirect calorimetry. Non-resting energy expenditure (NREE) was calculated as NREE = TEE - (REE + TEF). Subjects then gained or lost 10% of their body weight and were restudied as described above. All measures of TEE were significantly correlated (dietTEE vs. chamberTEE r2 = 0.75; dietTEE vs. isotopeTEE r2 = 0.88; isotopeTEE vs. chamberTEE r2 = 0.73; P < 0.0001). ChamberTEE (mean +/- SE = 2,107 +/- 64 kcal/day) was approximately 20% lower than either dietTEE (2,536 +/- 94 kcal/day, P < 0.0001) or isotopeTEE (2,564 +/- 83 kcal/day, P < 0.0001). When data were normalized to metabolic mass, weight gain of 10% was associated with significant increases in dietTEE (P < 0.005) and isotopeTEE (P < 0.05) but not chamberTEE; weight loss of 10% was associated with significant reductions in dietTEE (P < 0.005) and isotopeTEE (P < 0.05) but not chamberTEE. We conclude that measures of energy expenditure obtained in a highly controlled environment by caloric titration (dietTEE) or differential excretion rates of 2H2O and H(2)18O (isotopeTEE) are not significantly different and that measurements of TEE obtained in a respiratory chamber (chamberTEE) are significantly lower than dietTEE or isotopeTEE, probably largely due to limitations on physical activity in the chamber.

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Epidemiologic studies consistently report associations between obesity and dietary fat but not total energy intake. We measured ad libitum food intake in a laboratory setting and evaluated its relation to body weight and composition, energy expenditure, and macronutrient utilization in 28 women of Pima-Papago heritage (aged 27 +/- 7 y, 85.3 +/- 19.0 kg, 44 +/- 6% body fat; means +/- SD). All women were studied during the follicular phase of the menstrual cycle. After a 4-d weight-maintenance period, the volunteers selected their food for 5 d from computerized vending machines offering a variety of familiar and preferred foods, ie, a "cafeteria diet". Twenty-four-hour energy expenditure and substrate oxidation were measured in a respiratory chamber on the 4th d o weight maintenance and the 5th d of ad libitum intake. Average ad libitum intake was 13,732 +/- 4238 kJ/d (11 +/- 1% protein, 40 +/- 1% fat, 49 +/- 4% carbohydrate), ie, moderate overeating by 27 +/- 37% above weight maintenance requirements (range: -27% to 124%). Percent body fat correlated with daily energy intake (r = 0.53, P < 0.01), the degree of overeating (r = 0.41, P < 0.05), and the selection of a diet higher in fat and lower in carbohydrate (r = 0.70 and r = -0.63, respectively, P < 0.001). Excess carbohydrate intake caused an increase in carbohydrate oxidation (r = 0.51, P < 0.01), whereas excess fat intake resulted in a decrease in fat oxidation (r = -0.53, P < 0.01) and thus a positive fat balance of 85 +/- 65 g/d. The positive relations among degrees of obesity, dietary fat intake and overeating, and the fact that dietary fat does not induce fat oxidation, support the hypothesis that dietary fat promotes obesity in women.

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A low metabolic rate for a given body size and body composition and a low ratio of fat to carbohydrate oxidation predict body weight gain. Such metabolic traits could also explain, in part, the propensity of previously obese (postobese) individuals to regain weight after dieting. We studied 11 postobese volunteers (4 males, 7 females; aged 43 +/- 13 y, weighing 80.6 +/- 10.2 kg, with 30 +/- 7% body fat; x +/- SD) who lost 57 +/- 38 kg (23-139 kg) over 14 +/- 12 mo (6-48 mo) on various diet programs and had maintained this weight loss for > or = 2 mo (2-72 mo; 21 +/- 27 mo). After > or = 2 d of a weight-maintenance diet on a metabolic ward, 24-h energy expenditure and ratio of fat to carbohydrate oxidation were measured in a respiratory chamber. Compared with a control group (n = 110) with similar physical characteristics (aged 43 +/- 14 y, weighing 79.5 +/- 11.4 kg, with 30 +/- 12% body fat), [sequence: see text] postobese individuals had similar energy expenditures adjusted for fat-free mass, fat mass, age, and sex, but significantly higher respiratory quotients over 24 h (0.883 +/- 0.026 compared with 0.863 +/- 0.024, P < 0.01) and during sleep, 10 h after the last meal (0.894 +/- 0.063 compared with 0.845 +/- 0.055). These results suggest that postobese individuals have low rates of fat oxidation that may explain their propensity to regain weight.(ABSTRACT TRUNCATED AT 250 WORDS)

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OBJECTIVE: To investigate the relationship between obesity and ad libitum food intake (quantity and composition) and to assess the impact of ad libitum food intake on energy expenditure and macronutrient oxidation. DESIGN: Male volunteers were first fed a weight maintaining diet for at least 4 days before selecting their food for the next 5 days from two computerized vending machines offering a variety of familiar, palatable foods. 24-h energy expenditure (24EE) and substrate oxidation were measured in a respiratory chamber on the last day of each weight maintenance and ad libitum intake periods. SETTING: Ten day admission on a metabolic research ward. SUBJECTS: Thirty-four non-diabetic Pima Indian males covering a wide range of body weight and body composition (30 +/- 8 y, 102.1 +/- 30.2 kg, 34 +/- 9% body fat, mean +/- s.d.). RESULTS: Weight maintenance requirements averaged 2913 +/- 342 kcal/d. Energy intake during the ad libitum period increased to 4550 +/- 921 kcal/d (12 +/- 1% protein, 40 +/- 4% fat, 48 +/- 4% carbohydrate) i.e., a spontaneous overeating by 54 +/- 32% above weight maintenance requirement, resulting in a 0.9 +/- 1.0 kg body weight gain. Neither the composition of the selected diet nor the degree of overeating was associated with physical characteristics, such as body weight and body composition. When compared with baseline, spontaneous overeating on day 5 was associated with a 396 +/- 233 kcal/d increase in 24EE, a 607 +/- 503 kcal/d increase in carbohydrate oxidation, a 214 +/- 392 kcal/d decreased in lipid oxidation (P < 0.01), and no change in protein oxidation. Increased carbohydrate oxidation correlated with the excess carbohydrate intake (r = 0.69, P = 0.0001) accounting for 68 +/- 13% (mean +/- s.e.e.) of the excess, whereas excess fat intake was not oxidized. CONCLUSION: In response to spontaneous overfeeding on a mixed 'cafeteria diet', excess carbohydrate intake is oxidized, suggesting a physiological control of carbohydrate stores, whereas excess fat intake is channeled toward fat stores. None of the observed changes were related to indices of obesity.

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Directional coronary atherectomy (DCA) has proven to be an effective treatment for coronary artery disease, both in multiple anatomical locations and in various clinical settings. Little has been published, however, regarding efficacy of DCA for treatment of acute myocardial infarction (MI). This brief report reviews our early experience with DCA in this new role. Twelve patients presenting from April 1993 through February 1994 were identified by review of the DCA Registry at Hamot Medical Center. The group comprised six men and six women mean age 60 years (range 39-81 years). Patients were administered oral aspirin and intravenous nitroglycerin Heparin dose was titrated to maintain ACTs > 300 seconds. DCA was performed using 9.5-, 10-, and 11Fr guiding catheters. Seven Fr EX, 7Fr graft, 7Fr surlyn, and 6Fr EX devices were used. Predilation and/or postdilation with balloon angioplasty was performed when clinically indicated. Postprocedure stenoses were determined using comparable orthogonal angiographic views. Lesions were measured by manual caliper assessment and tissue weights were obtained from all specimens. The procedural success rate was 92% (11/12) and the mean postprocedural diameter stenosis was 15% (range -20% to 52%). The mean tissue weight from atherectomy specimens was 16 mg (range 7.6-35 mg). The mean time from onset of pain to reperfusion was 2.8 hours (range 40 min to 5.5 hours). Clinical success was achieved in 83% (10/12) of patients. Two deaths occurred in patients presenting with cardiogenic shock. Ten patients experienced no ischemic events, heart failure, or arryhthmias following their interventional procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

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