Intra-islet glucagon signalling regulates beta-cell connectivity, first-phase insulin secretion and glucose homoeostasis.

OBJECTIVE: Type 2 diabetes (T2D) is characterised by the loss of first-phase insulin secretion. We studied mice with ß-cell selective loss of the glucagon receptor (Gcgrfl/fl X Ins-1Cre), to investigate the role of intra-islet glucagon receptor (GCGR) signalling on pan-islet [Ca2+]I activity and insulin secretion. METHODS: Metabolic profiling was conducted on Gcgrß-cell-/- and littermate controls. Crossing with GCaMP6f (STOP flox) animals further allowed for ß-cell specific expression of a fluorescent calcium indicator. These islets were functionally imaged in vitro and in vivo. Wild-type mice were transplanted with islets expressing GCaMP6f in ß-cells into the anterior eye chamber and placed on a high fat diet. Part of the cohort received a glucagon analogue (GCG-analogue) for 40 days and the control group were fed to achieve weight matching. Calcium imaging was performed regularly during the development of hyperglycaemia and in response to GCG-analogue treatment. RESULTS: Gcgrß-cell-/- mice exhibited higher glucose levels following intraperitoneal glucose challenge (control 12.7 mmol/L ± 0.6 vs. Gcgrß-cell-/- 15.4 mmol/L ± 0.0 at 15 min, p = 0.002); fasting glycaemia was not different to controls. In vitro, Gcgrß-cell-/- islets showed profound loss of pan-islet [Ca2+]I waves in response to glucose which was only partially rescued in vivo. Diet induced obesity and hyperglycaemia also resulted in a loss of co-ordinated [Ca2+]I waves in transplanted islets. This was reversed with GCG-analogue treatment, independently of weight-loss (n = 8). CONCLUSION: These data provide novel evidence for the role of intra-islet GCGR signalling in sustaining synchronised [Ca2+]I waves and support a possible therapeutic role for glucagonergic agents to restore the insulin secretory capacity lost in T2D.

Long-Term Biochemical Control of a Prospective Cohort of Prostate Cancer Patients Treated With Interstitial Brachytherapy Versus Radical Prostatectomy.

AIMS: To report long-term oncological outcomes of men treated prospectively as part of the American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT) at our institution. MATERIALS AND METHODS: In 2003-2004, patients eligible for SPRIT attended a multidisciplinary educational session, following which they could choose radical prostatectomy, low dose rate brachytherapy (LDR-BT) or randomisation to SPIRIT. Biochemical failure was determined by the accepted definitions of a prostate-specific antigen (PSA) level ≥0.2 ng/ml after radical prostatectomy and the Phoenix definition of PSA ≥2 ng/ml above the nadir after LDR-BT. A sensitivity analysis, using a PSA >0.5 ng/ml to define biochemical failure after LDR-BT and a threshold PSA ≥0.2 ng/ml, was carried out to test the robustness of the results. To account for the competing risk of death, Gray's test was used to test the equality of the cumulative incidence function of biochemical failure between treatment groups. The Kaplan-Meier method was used to estimate overall survival and prostate cancer-specific survival. A P-value ≤0.05 was considered statistically significant. RESULTS: Of 156 patients, 100 received LDR-BT (15 after randomisation) and 56 underwent radical prostatectomy (15 after randomisation). The median follow-up was 12.6 and 14.7 years for LDR-BT and radical prostatectomy, respectively. The median age was 60 years; the median pre-treatment PSA was 5.5 (interquartile range 4.3-7.1). No significant differences in patient characteristics were found between groups. Two patients received adjuvant radiotherapy after radical prostatectomy. The cumulative incidence function of biochemical failure was 0%, 1.1% and 2.4% at 5, 10 and 15 years, respectively, in the LDR-BT arm versus 8.5%, 15.8% and 15.8% in the radical prostatectomy arm (P < 0.001). These results were consistent when varying the definition of biochemical failure defined as PSA ≥0.5 ng/ml (P = 0.01). At 15 years, overall survival was higher in patients treated with radical prostatectomy compared with those treated with LDR-BT; however, no statistical difference was found in prostate cancer-specific survival. CONCLUSION: In low-risk prostate cancer patients, LDR-BT offers excellent long-term oncological outcomes comparable with radical prostatectomy, in addition to the previously reported advantage for LDR-BT in urinary and sexual quality of life domains and patient satisfaction.

Microplastics in different water samples (seawater, freshwater, and wastewater): Methodology approach for characterization using micro-FTIR spectroscopy.

Microplastics of millimeter dimensions have been widely investigated in environmental compartments and today, studies are mainly focused on particles of smaller dimensions (< 500 µm). However, as there are no relevant standards or policies for the preparation and analysis of complex water samples containing such particles, the results may be questionable. Therefore, a methodological approach for 10 µm to 500 µm microplastic analysis was developed using µ-FTIR spectroscopy coupled with the siMPle analytical software. This was undertaken on different water samples (sea, fresh, and wastewater) taking into consideration rinsing water, digestion protocols, collection of microplastics, and sample characteristics. Ultrapure water was the optimal rinsing water and ethanol was also proposed with a mandatory previous filtration. Although water quality could give some guidelines for the selection of digestion protocols, it is not the only decisive factor. The methodology approach by µ-FTIR spectroscopy was finally assessed to be effective and reliable. This improved quantitative and qualitative analytical methodology for microplastic detection can then be used to assess the removal efficiency of conventional and membrane treatment processes in different water treatment plants.

Microplastics in different water samples (seawater, freshwater, and wastewater): Removal efficiency of membrane treatment processes.

The distribution and fate of microplastics in different water sources and their treatment plants (seawater, three municipal wastewaters, a pharmaceutical factory wastewater, and three drinking waters) in France were studied. Currently, research in this field is still under exploration since almost no relevant standards or policies have been introduced for the detection, the removal, or the discharge of microplastics. This study used an improved quantitative and qualitative analytical methodology for microplastic detection by µ-FTIR carried out with siMPle analytical software. By investigation, wastewater was determined to contain the most abundant microplastics in quantity (4,203-42,000 MP·L-1), then followed by surface water/groundwater (153-19,836 MP·L-1) and seawater (around 420 MP·L-1). Polyethylene was the dominant material in almost all water types followed by polypropylene, polystyrene, and polyethylene terephthalate. Almost all treatment technologies could remove microplastics whatever the feed water types and concentration of microplastics, though some treatment processes or transport pipes could cause additional contamination from microplastics. The four WWTPs, three DWTPs, and SWTP in France provided, respectively, 87.8-99.8%, 82.3-99.9%, 69.0-96.0% removal/retention of MPs in quantity, and provided 97.3-100%, 91.9-99.9%, 92.2-98.1% removal/retention of MPs in surface area. Moreover, ultrafiltration was confirmed to be an effective technology for microplastic retention and control of dimensions of microplastics in smaller ranges both in field-scale and lab-scale experiments. The 200 kDa ultrafiltration membrane could retain 70-100% and 80-100% of microplastics in quantity and in surface area, respectively.

Nitrogen and carbon removal from anaerobic digester effluents with low carbon to nitrogen ratios under feammox conditions.

Removal of nitrogen and carbon from anaerobic digester (AD) effluents is challenging for currently available technologies. Herein, effective treatment for real AD effluents was achieved via the feammox process by using a Multistage Feammox Bioreactor (MSFB). The reactor achieved the best performance with AD effluent of a low carbon to nitrogen (C/N) ratio of 2.5. A 6-day retention time reached removal efficiencies for NH4+ and COD at 99 % and 97 %, respectively, with a thorough conversion of NH4+ to N2. Accordingly, the MSFB achieved removal rates for N and C of 14 and 34 mg L-1 d-1, respectively. The C/N ratio of 2.5 is regarded to be the critical point above which the feammox is shifted to conventional iron reduction with organic carbon. Iron-reducing bacteria of the γ- Proteobacteria (Pseudomonas and Acinetobacter), and δ- Proteobacteria (Geobacter) were dominant in the MSFB and were supposed to drive the feammox process.

Physiologically Based Pharmacokinetic Modeling To Guide Management of Drug Interactions between Elexacaftor-Tezacaftor-Ivacaftor and Antibiotics for the Treatment of Nontuberculous Mycobacteria.

Nontuberculous mycobacteria (NTM) are the pathogens of concern in people with cystic fibrosis (pwCF) due to their association with deterioration of lung function. Treatment requires the use of a multidrug combination regimen, creating the potential for drug-drug interactions (DDIs) with cystic fibrosis transmembrane conductance regulator (CFTR)-modulating therapies, including elexacaftor, tezacaftor, and ivacaftor (ETI), which are eliminated mainly through cytochrome P450 (CYP) 3A-mediated metabolism. An assessment of the DDI risk for ETI coadministered with NTM treatments, including rifabutin, clofazimine, and clarithromycin, is needed to provide appropriate guidance on dosing. The CYP3A-mediated DDIs between ETI and the NTM therapies rifabutin, clarithromycin, and clofazimine were evaluated using physiologically based pharmacokinetic (PBPK) modeling by incorporating demographic and physiological "system" data with drug physicochemical and in vitro parameters. Models were verified and then applied to predict untested scenarios to guide continuation of ETI during antibiotic treatment, using ivacaftor as the most sensitive CYP3A4 substrate. The predicted area under the concentration-time curve (AUC) ratios of ivacaftor when coadministered with rifabutin, clofazimine, or clarithromycin were 0.31, 2.98, and 9.64, respectively, suggesting moderate and strong interactions. The simulation predicted adjusted dosing regimens of ETI administered concomitantly with NTM treatments, which required delayed resumption of the standard dose of ETI once the NTM treatments were completed. The dosing transitions were determined based on the characteristics of the perpetrator drugs, including the mechanism of CYP3A modulation and their elimination half-lives. This study suggests increased doses of elexacaftor/tezacaftor/ivacaftor 200/100/450 mg in the morning and 100/50/375 mg in the evening when ETI is coadministered with rifabutin and reduced doses of elexacaftor/tezacaftor 200/100 mg every 48 h (q48h) and ivacaftor 150 mg daily or a dose of elexacaftor/tezacaftor/ivacaftor 200/100/150 mg q72h when coadministered with clofazimine or clarithromycin, respectively. Importantly, the PBPK simulations provide evidence in support of the use of treatments for NTM in pwCF receiving concomitant dose-adjusted ETI therapy.

Air dispersal of meticillin-resistant Staphylococcus aureus in residential care homes for the elderly: implications for transmission during the COVID-19 pandemic.

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) infections are rampant in hospitals and residential care homes for the elderly (RCHEs). AIM: To analyse the prevalence of MRSA colonization among residents and staff, and degree of environmental contamination and air dispersal of MRSA in RCHEs. METHODS: Epidemiological and genetic analysis by whole-genome sequencing (WGS) in 12 RCHEs in Hong Kong. FINDINGS: During the COVID-19 pandemic (from September to October 2021), 48.7% (380/781) of RCHE residents were found to harbour MRSA at any body site, and 8.5% (8/213) of staff were nasal MRSA carriers. Among 239 environmental samples, MRSA was found in 39.0% (16/41) of randomly selected resident rooms and 31.3% (62/198) of common areas. The common areas accessible by residents had significantly higher MRSA contamination rates than those that were not accessible by residents (37.2%, 46/121 vs. 22.1%, 17/177, P=0.028). Of 124 air samples, nine (7.3%) were MRSA-positive from four RCHEs. Air dispersal of MRSA was significantly associated with operating indoor fans in RCHEs (100%, 4/4 vs. 0%, 0/8, P=0.002). WGS of MRSA isolates collected from residents, staff and environmental and air samples showed that ST 1047 (CC1) lineage 1 constituted 43.1% (66/153) of all MRSA isolates. A distinctive predominant genetic lineage of MRSA in each RCHE was observed, suggestive of intra-RCHE transmission rather than clonal acquisition from the catchment hospital. CONCLUSION: MRSA control in RCHEs is no less important than in hospitals. Air dispersal of MRSA may be an important mechanism of dissemination in RCHEs with operating indoor fans.

Miconazole and terbinafine induced reactive oxygen species accumulation and topical toxicity in human keratinocytes.

There are an estimated 1 billion cases of superficial fungal infection globally. Fungal pathogens form biofilms within wounds and delay the wound healing process. Miconazole and terbinafine are commonly used to treat fungal infections. They induce the accumulation of reactive oxygen species (ROS) in fungi, resulting in the death of fungal cells. ROS are highly reactive molecules, such as oxygen (O2), superoxide anion (O2•-), hydrogen peroxide (H2O2) and hydroxyl radicals (•OH). Although ROS generation is useful for killing pathogenic fungi, it is cytotoxic to human keratinocytes. To the best of our knowledge, the effect of miconazole and terbinafine on HaCaT cells has not been studied with respect to intracellular ROS stimulation. We hypothesized that miconazole and terbinafine have anti-wound healing effects on skin cells when used in antifungal treatment because they generate ROS in fungal cells. We used sulforhodamine B protein staining to investigate cytotoxicity and 2',7'-dichlorofluorescein diacetate to determine ROS accumulation at the 50% inhibitory concentrations of miconazole and terbinafine in HaCaT cells. Our preliminary results showed that topical treatment with miconazole and terbinafine induced cytotoxic responses, with miconazole showing higher cytotoxicity than terbinafine. Both the treatments stimulated ROS in keratinocytes, which may induce oxidative stress and cell death. This suggests a negative correlation between intracellular ROS accumulation in keratinocytes treated with miconazole or terbinafine and the healing of fungi-infected skin wounds.

Robotic retroperitoneal lymph node dissection for primary and post-chemotherapy testis cancer.

The role of retroperitoneal lymph node dissection (RPLND) in testicular cancer is well established in both the primary and post-chemotherapy setting. The aim of this study was to report our 2 years oncological outcomes of robotic RPLND. A retrospective review was performed of all patients undergoing robotic RPLND by a single surgeon at Princess Margaret Cancer Centre. Demographic, perioperative, and oncologic data were analyzed using descriptive statistics. Between September 2014 and June 2020, 141 patients underwent an RPLND [33 (23.4%) were primary, 108 (76.6%) were post-chemotherapy]. 27 (19.1%) patients underwent a robotic bilateral template nerve-sparing RPLND. RPLND indication was primary (i.e. pre-chemotherapy) in 18 (66.7%), and post-chemotherapy in 9 (33.3%) patients. Stage at RPLND was 2A (n = 15, 55.6%), 2B (n = 9, 33.3%), 2C (n = 1, 3.7%) and 3 (n = 2, 7.4%). Median OR time (incision to closure) was 525 min and blood loss was 200 ml. Nerve sparing was performed in all but one case. Six (22.2%) adjuvant procedures were performed including two (7.4%) vascular repairs. Median length of stay was 2 days. Viable tumor was detected in 17 (63%) and teratoma in 9 (33.3%). Median follow-up was 31.3 months. No adjuvant chemotherapy was given. Three patients (11.1%) relapsed: 2 out-of-field and 1 with both in-field and out-of-field disease. Robotic RPLND can be performed safely. Long-term follow-up of series such as ours, enriched with patients with viable disease and/or teratoma, and not treated with adjuvant chemotherapy is required to ensure oncological outcomes are comparable to the open approach.

Association between school racial/ethnic composition during adolescence and adult health.

OBJECTIVES: School racial/ethnic segregation in U.S. schoolsDifferences in school racial/ethnic composition may increase health disparities by concentrating educational opportunities that confer long-term health benefits in schools serving predominantly wwhite students. For racial minority students, high concentrations of white students may increase exposure to racismis also associated with psychologicstress, which may ultimately reduceing the long-term health benefits from educational opportunities. Meanwhile associations of racial/ethnic academic tacking within schools and health have been mixed. We sought to test whether: 1) differences in racial/ethnic composition between schools and, 2) racial/ethnic distribution of students in academic tracks within schools are associated with long-term health benefits or risks for white, Black and Latinx students. METHODS: We analyzed the National Longitudinal Study of Adolescent to Adult Health (12,438 participants, collected 1994-2008), to test whether the school-level segregation (percent of non-Latinx white students at participants' school during adolescence) was associated with adult health outcomes at ages 18-26 & 24-32, controlling for contextual factorscomparing Black, Latinx, and white students, and controlling for contextualf factors. A secondary analysis explored whether racial/ethnic cohorting across levels of English courses was associated with each health outcome. RESULTS: Attending a school with a higher percent of white students was associated with higher adult depression scores, substance abuse, and worse self-rated health for black Black students; lower depression scores, better self-rated health, and alcohol abuse for white students; and no health differences for Latinx students. Greater within school racial/ethnic cohorting across English courses was associated with increased odds of alcohol abuse for white students; decreased odds of alcohol abuse for Black and Latinx students; and decreased odds of drug abuse for Black students. CONCLUSION: Among Bblack youth, attending a school with a higher percentage of white students is associated with worse behavioral health in adulthood. Understanding the potential impacts of school racial/ethnic composition on health is critical to designing policies that maximize access to opportunity and health.Education policies should comprehensively address school quality and racism to maximize adult health.

It's not just an ileus: disparities associated with ileus following ventral hernia repair.

PURPOSE: We sought to identify risk factors associated with postoperative ileus following ventral hernia repair. METHODS: Utilizing the Nationwide Inpatient Sample (NIS) from 2008 to 2012, we identified adult patients that underwent either open or laparoscopic hernia repair for umbilical and ventral hernias with a diagnosis of umbilical/ventral hernia. We excluded cases with diagnosis of obstruction and bowel gangrene that underwent bowel resection, or with missing data. Risk variables of interest were age, sex, race, income status, insurance status, elective admission, comorbidity status (using the validated van Walraven Score), complications (mechanical, respiratory, postoperative infection, cardiovascular, intraoperative), morbid obesity, procedure type, conversion to open, mesh use, hospital type (rural, urban non-teaching, urban teaching), bed size, and region (northeast, midwest, south, west). Univariate analysis comparing patients with ileus vs control was performed. We then performed multivariable analysis using logistic regression, adjusting for all the risk variables, with ileus as the dependent variable. RESULTS: 30,912 patients were identified that met criteria. Of these, 2660 (8.61%) had postoperative ileus during their stay at the hospital. Univariate analysis showed all risk variables were associated with development of ileus with the exception of income status (p = 0.2903), elective admission (p = 0.7989), mesh use (p = 0.3620), and hospital bed size (p = 0.08351). Median length of stay was 7 days in the ileus cohort vs 3 days in control (p < 0.0001). Median total charges (adjusted to 2012 dollars) was $54,819 vs $35,058 (p < 0.0001). We then performed logistic regression adjusting for all risk variables and found that age (OR 1.66, p < 0.0001), male sex (OR 1.51, p < 0.0001), Black race (OR 1.49, p < 0.0001), comorbidity status (OR 1.12, p < 0.0001), laparoscopic cases converted to open (OR 1.55, p < 0.0001), postoperative complications (mechanical: OR 2.32, p < 0.0001, respiratory: OR 1.54, p < 0.0001, postoperative infection: OR 2.12, p < 0.0001, cardiovascular: OR 1.57, p = 0.0006, intraoperative: OR 1.29, p = 0.0200) were independently associated with increased risk of ileus. However, laparoscopic vs open (OR 0.76, p < 0.0001), elective admission (OR 0.91, p = 0.0378), and northeast vs south hospital region (OR 0.74, p < 0.0001) were independently associated with decreased risk of ileus. CONCLUSION: We performed a large observational study looking for risk factors associated with ileus following ventral hernia repair. Race and region of treatment are independent risk factors associated with ileus following ventral hernia repair, and a potential source of disparities in care and increased admission length and higher cost of care. Further prospective studies are warranted.

International Comparison of Six Basic eHealth Indicators Across 14 Countries: An eHealth Benchmarking Study.

BACKGROUND: Many countries adopt eHealth applications to support patient-centered care. Through information exchange, these eHealth applications may overcome institutional data silos and support holistic and ubiquitous (regional or national) information logistics. Available eHealth indicators mostly describe usage and acceptance of eHealth in a country. The eHealth indicators focusing on the cross-institutional availability of patient-related information for health care professionals, patients, and care givers are rare. OBJECTIVES: This study aims to present eHealth indicators on cross-institutional availability of relevant patient data for health care professionals, as well as for patients and their caregivers across 14 countries (Argentina, Australia, Austria, Finland, Germany, Hong Kong as a special administrative region of China, Israel, Japan, Jordan, Kenya, South Korea, Sweden, Turkey, and the United States) to compare our indicators and the resulting data for the examined countries with other eHealth benchmarks and to extend and explore changes to a comparable survey in 2017. We defined "availability of patient data" as the ability to access data in and to add data to the patient record in the respective country. METHODS: The invited experts from each of the 14 countries provided the indicator data for their country to reflect the situation on August 1, 2019, as date of reference. Overall, 60 items were aggregated to six eHealth indicators. RESULTS: Availability of patient-related information varies strongly by country. Health care professionals can access patients' most relevant cross-institutional health record data fully in only four countries. Patients and their caregivers can access their health record data fully in only two countries. Patients are able to fully add relevant data only in one country. Finland showed the best outcome of all eHealth indicators, followed by South Korea, Japan, and Sweden. CONCLUSION: Advancement in eHealth depends on contextual factors such as health care organization, national health politics, privacy laws, and health care financing. Improvements in eHealth indicators are thus often slow. However, our survey shows that some countries were able to improve on at least some indicators between 2017 and 2019. We anticipate further improvements in the future.

Obesity and surgical complications of pancreaticoduodenectomy: An observation study utilizing ACS NSQIP.

BACKGROUND: An estimated 38% of US adults are obese. Obesity is associated with socioeconomic disparities and increased rates of comorbidities, and is a known risk factor for development of pancreatic cancer. As a fourth leading cause of death in the United States, pancreatic cancer is commonly treated with a pancreatico-duodenectomy (PD), or Whipple procedure. Data regarding the effects of obesity on post-operative complication rate primarily comes from specialized centers, however the results are mixed. Our aim is to elucidate the effects that obesity has on outcomes after PD for pancreatic head cancer using a national prospectively maintained clinical database. METHOD: The 2010-2015 American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) Participant Use Files (PUF) were used as the data source. We identified cases in which PD was performed (CPT code 48150) in the setting of a postoperative diagnosis of pancreatic cancer (ICD9 code 157.0). We excluded cases that had emergency admissions, BMI ≤18.5 kg/m2, intraoperative wound classification of III or IV, and disseminated cancer. Cases with missing BMI, preoperative albumin, operative time, LOS data were also excluded. Multiple imputation for missing sex, race, functional status, and ASA classification using chained equations was performed.16 Patients that had BMI ≥30 kg/m2 were considered obese, and patients with BMI <30 kg/m2 were used as control. RESULTS: 3484 patients underwent pancreaticoduodenectomy for pancreatic cancer. 860 patients were identified as obese. Propensity score analysis was performed matching age, sex, race, functional status, presence of dyspnea, diabetes, hypertension, acute renal failure, dialysis dependence, ascites, steroid use, bleeding disorders, history of chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), weight loss, American Society of Anesthesiologists (ASA) classification, and preoperative albumin levels. After matching, obese patients had higher risk of 30-day postoperative complications compared to control, including organ space wound infections (OR 1.38, 95% CI 1.07-1.79, p = 0.0128), returning to the operating room (OR 1.39, 95% CI 1.01-1.91, p = 0.0461), failure to extubate for greater than 48 h (OR 1.60, 95% CI 1.09-2.34, p = 0.0153), death (OR 1.68, 95% CI 1.01-2.78, p = 0.0453), septic shock (OR 2.22, 95% CI 1.46-3.38, p = 0.0002), pulmonary embolism (OR 2.42, 95% CI 1.07-5.45, p = 0.0332), renal insufficiency (OR 2.67, 95% CI 1.33-5.38, p = 0.0058). Sensitivity analysis yielded similar results with the exception of risk for return to the operating room, death, and pulmonary embolism, P > .05. CONCLUSION: In this large observational study using a national clinical database, obese patients undergoing PD for head of pancreas cancer had increased risk of postoperative complications and mortality in comparison to controls.

Quality of life and defecative function 10 years or longer after posterior sagittal anorectoplasty and laparoscopic-assisted anorectal pull-through for anorectal malformation.

PURPOSE: In our center, patients with anorectal malformation, including males with recto-vesical (RV)/recto-bladder neck (RBN)/recto-prostatic urethral (RU) fistulas, and females with recto-vaginal (RV) fistulas have been treated by posterior sagittal anorectoplasty (PSARP) before 2000, and by laparoscopic-assisted anorectal pull-through (LAARP) thereafter. We would like to compare the quality of life (QOL) and long-term defecative function between these two groups of patients 10 years after reconstructive surgery. METHODS: Patients who underwent LAARP between 2001 and 2005 were compared with historical controls treated with PSARP between 1996 and 2000. Degrees of continence were graded by the Krickenbeck classification and Kelly's score. QOL was assessed by Hirschsprung's disease/Anorectal Malformation Quality of Life (HAQL) questionnaire. Results were compared using Chi-square test and t test. RESULTS: There were 14 LAARP and 7 PSARP patients. All attained voluntary bowel movements. Moderate to severe soiling (Krickenbeck Grade 2 and 3) was found in 3/14 LAARP (21.4%) and 1/7 PSARP (14.3%) patients, p = 1.00. Constipation requiring use of laxatives was present in 3/14 LAARP (28.6%) and 1/7 PSARP (14.3%) patients, p = 0.62. Mean Kelly's scores were 3.79 ± 0.98 (LAARP) and 4.71 ± 1.25 (PSARP), p = 0.12. No patient required Malone antegrade continence enema (MACE). The QOL scores based on the HAQL questionnaire were comparable between the two groups in all areas except social functioning, in which the LAARP patients attained a significantly lower mean score (26.4 vs 71.7, p = 0.0001). CONCLUSION: The 10-year outcome between LAARP and PSARP patients in terms of QOL and defecative function is comparable. Impairment in social functioning in these patients is reflected by the self-reported lower level of functioning.

Boom boom pow: Shock-facilitated aqueous alteration and evidence for two shock events in the Martian nakhlite meteorites.

Nakhlite meteorites are ~1.4 to 1.3 Ga old igneous rocks, aqueously altered on Mars ~630 Ma ago. We test the theory that water-rock interaction was impact driven. Electron backscatter diffraction demonstrates that the meteorites Miller Range 03346 and Lafayette were heterogeneously deformed, leading to localized regions of brecciation, plastic deformation, and mechanical twinning of augite. Numerical modeling shows that the pattern of deformation is consistent with shock-generated compressive and tensile stresses. Mesostasis within shocked areas was aqueously altered to phyllosilicates, carbonates, and oxides, suggesting a genetic link between the two processes. We propose that an impact ~630 Ma ago simultaneously deformed the nakhlite parent rocks and generated liquid water by melting of permafrost. Ensuing water-rock interaction focused on shocked mesostasis with a high density of reactive sites. The nakhlite source location must have two spatially correlated craters, one ~630 Ma old and another, ejecting the meteorites, ~11 Ma ago.

A prospective observational study on the stress levels at the time of embryo transfer and pregnancy testing following in vitro fertilisation treatment: a comparison between women with different treatment outcomes.

OBJECTIVE: To ascertain whether stress biomarkers and psychological indices of stress may predict both conception and miscarriage rates in women undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI). DESIGN: Prospective observational study. SETTING: A university-affiliated tertiary hospital. POPULATION: Infertile women who were undergoing fresh or frozen IVF/ICSI cycles. METHODS: Women were recruited to (1) complete validated psychological questionnaires (visual analogue scale of stress, state-trait anxiety inventory, perceived stress scale, fertility problem inventory, Beck depression inventory, and general health questionnaire), at the time of embryo transfer (ET) and pregnancy testing (PT), and (2) provide saliva samples for α-amylase (sAA) measurement before and after ET and at PT. MAIN OUTCOME MEASURES: Women were grouped according to subsequent reproductive outcome; scores/levels of all tests were then compared between groups at each time-point. RESULTS: In all, 197 women completed the study, of which 92 conceived and 28 miscarried. The level of psychological stress, as measured by questionnaires, was highest at the time of PT, whereas the level of biological stress as measured by sAA level (IU/l) post-ET (1.8 × 105  ± 1.5 × 105 ) was significantly (P < 0.001) higher than pre-ET (1.2 × 105  ± 1.0 × 105 ) and at PT (1.0 × 105  ± 1.1 × 105 ). However, there was no difference in psychological scoring and in sAA levels between women who did or did not conceive and who had miscarried or had an ongoing pregnancy. CONCLUSIONS: The level of sAA is highest following ET, whereas psychological stress is highest at PT. However, neither stress level appeared to be of prognostic value in predicting conception or miscarriage. TWEETABLE ABSTRACT: Stress level fluctuated at different time-points, but it did not predict conception or miscarriage.