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LAMOTRIGINE, BIPOLAR disorder, GLOMERULAR filtration rate, and BODY mass index

Monitoring of lamotrigine levels is recommended in epilepsy. However, in bipolar disorders (BD), no study has described the therapeutic range in daily practice and factors being associated to it. We used retrospective data of individuals with BD, treated with lamotrigine, and included in the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort. We extracted clinical and biological data and explored associations between these variables and lamotrigine concentration/dose (C/D) ratio. The database included 675 individuals who received lamotrigine at inclusion, whose main characteristics were female sex (68.3%) and BD type 2 (52.1%). Data about lamotrigine C/D ratio were available for 205 individuals. Lamotrigine C/D ratio was significantly associated with: Body Mass Index (BMI) (r =-0.159), estimated GFR (glomerular filtration rate) (r =-0.228), total bilirubin (r = 0.241) and at a trend level, antidepressant co-prescription (U = 3169). The model obtained was: lamotrigine C/D ratio = 1.736 - 0.013*BMI + 0.095*total bilirubin (UI/L) - 0.007*eGFR (ml/min) + 0.210*AST/ALT – 0.004*GGT (UI/L) + 0.014*age (year) + 0.303*currently smoking (yes or no) – 0.588*antidepressant co-prescription (yes or no) – 0.357*gender (F = 1.899, p = 0.057, adjusted R2 = 0.11) Information about plasma lamotrigine C/D ratio were available for only 205 out of the 675 individuals in the database and has been obtained from different laboratories. The representativeness of the included sample may be questionable. This is the first study providing information on a large sample of individuals with BD regarding factors associated with lamotrigine C/D ratio. This study allows to propose a model of lamotrigine C/D ratio that would deserve further replication. [ABSTRACT FROM AUTHOR]

GALVANIC skin response, PERSONALITY, AFFECTIVE neuroscience, STIMULUS & response (Psychology), TASTE perception, TASTE receptors, and SYMPATHETIC nervous system

• Skin conductance responses to oral stimuli primarily reflect surprisingness. • Individual differences modulate skin conductance responses to oral stimuli. • Skin conductance reflects higher stimulus intensity only in some individuals. • High skin conductance bitter responders are more anxious and less emotionally stable. • Lower skin conductance responses are associated with a heightened taste perception. Measuring emotional responses to tastes and foods, using both self-reports and also implicit and physiological measurements is gaining attention. Among physiological measurements, skin conductance response (SCR) is one the most commonly used indicators of emotional activation but it has been rarely applied to taste and other oral stimuli and its interpretation is not yet clear. Furthermore, the effect of individual differences in SCR to tastes has been rarely taken into account. To address these issues, SCR to bitter, astringent, and sweet samples presented both at weak/moderate and moderate/strong intensity was recorded while eighty Italians, selected based on PROP (6-n-propylthiouracil) status (only Medium-Tasters), performed an implicit affective test. Samples were presented blind in aqueous solutions monadically in triplicate. Subjects (Ss) were asked to taste a sample, then a neutral face was briefly presented on a screen, and Ss were asked to indicate if they trusted the face (yes/no) and how much (on a 9-point Scale). Data on Ss' psychological traits (anxiety, sensation seeking, food neophobia, emotional stability) was also collected. Two clusters were identified based individual SCR. These clusters differed in their SCR mainly to strong bitterness, and partially to astringency, while they did not differ for their response to the sweet samples. The High bitter responders were more anxious and neurotic than Low bitter responders. For this cluster higher intensities induced higher SCR, but this was not found in the Low bitter responders cluster that tended to have higher SCR to the least intense samples. No differences in the implicit affective responses to samples were found between clusters. These results indicate that SCR to tastes reflect mainly different sources of arousal, such as novelty/surprisingness, quality and intensity of the stimuli, and this may change at an individual level. This suggests that measurement of SC can contribute to a better understanding of individual differences in taste and oral experience and could provide a link between taste responsiveness and sympathetic nervous system activity. [ABSTRACT FROM AUTHOR]

LIVER cells, HOMEOSTASIS, NON-alcoholic fatty liver disease, YAP signaling proteins, GENETIC overexpression, NUCLEOTIDE synthesis, and METABOLIC regulation

A primary role of the liver is to regulate whole body glucose homeostasis. Glucokinase (GCK) is the main hexokinase (HK) expressed in hepatocytes and functions to phosphorylate the glucose that enters via GLUT transporters to become glucose-6-phosphate (G6P), which subsequently commits glucose to enter downstream anabolic and catabolic pathways. In the recent years, hexokinase domain-containing-1 (HKDC1), a novel 5th HK, has been characterized by our group and others. Its expression profile varies but has been identified to have low basal expression in normal liver but increases during states of stress including pregnancy, nonalcoholic fatty liver disease (NAFLD), and liver cancer. Here, we have developed a stable overexpression model of hepatic HKDC1 in mice to examine its effect on metabolic regulation. We found that HKDC1 overexpression, over time, causes impaired glucose homeostasis in male mice and shifts glucose metabolism towards anabolic pathways with an increase in nucleotide synthesis. Furthermore, we observed these mice to have larger liver sizes due to greater hepatocyte proliferative potential and cell size, which in part, is mediated via yes-associated protein (YAP) signaling. [ABSTRACT FROM AUTHOR]

AFFECTIVE neuroscience, BITTERNESS (Taste), SWEETNESS (Taste), AFFECT (Psychology), STIMULUS intensity, TRUST, and STIMULUS & response (Psychology)

• Affect misattribution procedure was used to measure implicit responses to tastes. • Both chemosensory quality and intensity contributed to implicit affective responses. • Reaction times were faster for lower intensity positive stimuli. • Reaction times were faster for strong intensity negative stimuli. • Trustworthiness for faces was applied as a proxy for affective responses. Implicit measurements are indirect and could register emotions elicited by tasting without conscious awareness. While we know that some basic tastes such as sweetness and bitterness are innately liked or disliked, little is known about the affective responses to tactile sensations. It is also underexplored in which way the emotional responses to chemosensory stimuli are affected by the intensity of the stimulus. To address these issues an implicit method based on the Affect Misattribution Procedure using the judgment of trustworthiness to neutral faces, a proxy for valence, was developed using real tastes as primes (instead of pictures). Three different implicit measures were compared in an experiment in which 107 Italian PROP (6-n-propylthiouracil) Medium-Tasters were exposed to bitterness, astringency, and sweetness at weak/moderate and moderate/strong intensity. Samples were presented blind in aqueous solution monadically in triplicate. Participants were asked to taste a sample, then a neutral face was briefly presented on a screen, and participants were asked to indicate if they trusted the face (yes/no) and how much (on a 9-point Scale). Reaction times (RTs) for the yes/no responses were also collected. The data indicated that both taste qualities and intensity level influenced the yes/no trustworthiness judgements as well as the ratings and the reaction times. As expected, sweetness elicited the most positive affective responses and bitterness the most negative. Astringency elicited a positive response (but lower than sweetness) when it was presented at low intensity, while it elicited a more negative response when it was presented at higher intensity, and this effect was particularly evident when this was evaluated with the scale. Faster reaction times were observed for lower intensity stimuli that had been evaluated as positive but also for higher intensity stimuli that had been evaluated as negative. The results of the present study represent an advance in methodologies that tap implicit affective reactions to chemosensory qualities found in foods and beverages and that can be used to study food experience. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post‐discharge outcomes.Of 8298 patients in the European Society of Cardiology Heart Failure Long‐Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non‐use of angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers and beta‐blockers. In‐hospital death occurred in 3.3%. The prevalence of hyponatraemia and in‐hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in‐hospital mortality 6.9%), 11% Yes/No (in‐hospital mortality 4.9%), 8% No/Yes (in‐hospital mortality 4.7%), and 72% No/No (in‐hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In‐hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12‐month mortality was 19% and adjusted hazard ratios (95% confidence intervals) were for hyponatraemia Yes/Yes 1.60 (1.35–1.89), Yes/No 1.35 (1.14–1.59), and No/Yes 1.18 (0.96–1.45). For death or heart failure hospitalization they were 1.38 (1.21–1.58), 1.17 (1.02–1.33), and 1.09 (0.93–1.27), respectively.Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced heart failure and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in‐hospital and post‐discharge outcomes. Hyponatraemia developing during hospitalization (possibly depletional) was associated with lower risk. [ABSTRACT FROM AUTHOR]

RHINOPLASTY, CLEFT lip, PATIENT satisfaction, RESPIRATION, and QUESTIONNAIRES

Secondary rhinoplasty on patients with cleft is a challenging procedure, and the most important criterion for evaluating the surgery success is patient satisfaction even if it's subjective. To evaluate patient satisfaction following secondary cleft rhinoplasty with a specific assessment for patients with Unilateral Cleft Lip and Palate (UCLP). Our retrospective cross-sectional study is composed of 29 patients with UCLP with a mean age of 23 years old, who underwent secondary rhinoplasty between 2010 and 2021 in our department. The survey was conducted postoperatively using a cleft-nose specific custom designed questionnaire based on the Byrne questionnaire, over the phone. This satisfaction questionnaire comprises six questions about physical appearance and one question about functional aspect. Patients were asked to answer "yes" or "no" or to rate from 0 (no improvement) to 10 (perfect result) depending on the question. Twenty out of 29 people responded to the questionnaire, representing an answer rate of 69%. The average score given by the patient for nasolabial scar improvement was 7.2/10, and the one concerning global improvement was 8.2/10. All patients would be ready to undergo the same procedure again, knowing the final result. A functional improvement concerning breathing or snoring was reported in 45% of cases. All dorsum or tip issues were improved after surgery (P = 0,07). Our results demonstrate high patient satisfaction after cleft rhinoplasty, which encourages the continuation of this surgery. We would recommend the use of this simple questionnaire to allow a more accurate evaluation of patient outcomes. [ABSTRACT FROM AUTHOR]

CATALAN language, OPTIMALITY theory (Linguistics), LANGUAGE & languages, ACCOMMODATIONISM, and AUTOSEGMENTAL theory (Linguistics)

This paper aims at contributing to ascertain the principles of intonational grammar that lie behind the realization of nuclear contours and at presenting them in terms of Optimality Theory constraints. In order to do so, we analyse the prosody of the nuclear configuration of Southern Valencian Catalan yes-no questions, with special emphasis on situations where text-tune accommodation phenomena take place. The empirical data, which are analysed according to the principles of the autosegmental-metrical model, show a complex interplay of different phenomena at the text-tune interface, like vowel lengthening, tonal spreading, tonal retraction and intonation-driven schwa epenthesis. We argue that the variation detected in the data can be accounted for by the interaction of nine constraints (i.e., Max-IO(µp), Dep-IO(µs), Anchor(T%,Rt,IP,Rt), Anchor(L*,Rt,ˈσ,Rt), *Anchor(T,C), *Anchor(T,-voice), Share(T*,NC), Dep-IO(Associate), Max-IO(Associate)), whose ranking is established by means of a Stochastic Optimality Theory analysis. [ABSTRACT FROM AUTHOR]

SECOND language acquisition, DOMINANT language, CHINESE language, LANGUAGE & languages, NATIVE language, and NATURAL languages

And even though I do not think that most domain-general models of L SB 1 sb /L SB 2 sb acquisition are going to come under further scrutiny, Mazuka's distinction is likely to be valuable for domain-specific models of acquisition (of phonology). Yes, L SB 2 sb learners do not parse de-RCs in the same way as native speakers do, but that only indicates that they have not achieved ultimate attainment; not that there are fundamental differences in L SB 1 sb and L SB 2 sb processing. Martohardjono, Valian and Klein (MVK) take up the deficit and transfer accounts (d/t) of L SB 2 sb acquisition in their chapter, while looking at acquisition of tense. [Extracted from the article]

ANGIOKERATOMA corporis diffusum, PATIENTS, TREATMENT effectiveness, KIDNEY physiology, and SYMPTOMS

Clinical manifestations of classic Fabry disease (α-galactosidase A deficiency) usually occur in childhood, while complications involving major organs typically develop in adulthood. Outcomes of Fabry-specific treatment among young patients have not been extensively reported. Our aim was to analyze clinical outcomes among patients aged 5–30 years at initiation of treatment with agalsidase beta using data from the Fabry Registry (NCT00196742 , sponsor: Sanofi). Reported GLA variants were predicted to be associated with the classic phenotype or not classified in fabry-database.org. Linear mixed models were conducted to assess changes over ≥2-year follow-up in the estimated glomerular filtration rate (eGFR) stratified by low (LRI) and high (HRI) renal involvement (defined by proteinuria/albuminuria levels), and changes in interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) Z -scores stratified by median age at first treatment. Self-reports ('yes'/'no') of abdominal pain, diarrhea, chronic peripheral pain (denoting neuropathic pain), and acute pain crises at baseline were compared with reports after ≥0.5-year and ≥2.5-year follow-up using McNemar's test. Male (n = 117) and female patients (n = 59) with LRI initiated treatment at a median age of 19.9 and 23.6 years, respectively, and were followed for a median of 6.3 and 5.0 years, respectively. The eGFR slopes were −1.18 (P from 0 <0.001) and −0.92 mL/min/1.73 m2/year (P from 0 = 0.040), respectively. Males with HRI (n = 23, median UPCR 1.0 g/g), who started treatment at a median age of 26.7 years, had an eGFR slope of −2.39 mL/min/1.73 m2/year (P from 0 <0.001; P difference = 0.055, as compared with the slope of −1.18 mL/min/1.73 m2/year for LRI males) during a median follow-up of 5.6 years. Echocardiographic variables were stable among males, regardless of age, and among young females (median follow-up >5.5 years and ≥4.5 years, respectively). Older females (treatment initiation at median age 27.5 years) had a slope of LVPWT Z -scores of 0.18/year (n = 12, P from 0 = 0.028), whereas IVST Z -scores remained stable (n = 13, 0.10/year, P from 0 = 0.304) during a median follow-up of ≥3.7 years. These slopes did not significantly differ from slopes of younger females. Reports of chronic peripheral pain and acute pain crises by males, and of diarrhea and acute pain crises by females, significantly reduced after a median follow-up of ≥4.0 years. After a median follow-up of ≥5.4 years, reports of all four symptoms significantly decreased among males, whereas among females only reports of abdominal pain significantly decreased. During sustained treatment with agalsidase beta in young Fabry patients with a predicted classic phenotype or with unclassified GLA variants with similar characteristics, the decline in eGFR was modest among male and female patients with LRI. The greater decline in eGFR among older, proteinuric (i.e., HRI) males may suggest a benefit of earlier treatment. Overall, echocardiographic variables remained stable, particularly among males and younger females. Significant reductions in symptom reports occurred primarily among males after longer follow-up and were less noticeable among females. These observed trends are suggestive of an overall improvement after treatment in young patients, but warrant larger longitudinal studies. • Overall improvement after sustained agalsidase beta treatment in young Fabry patients. • Modest decrease in kidney function in patients with low renal involvement. • Greater decrease in kidney function in older, proteinuric male patients. • Stable echocardiographic variables among male and younger female patients. • Reductions in Fabry disease symptom reports particularly among male patients. [ABSTRACT FROM AUTHOR]

SPANISH language, CORPORA, DISCOURSE, and CONVERSATION

The aim of this paper is to describe the prosodic features --nuclear pitch configurations and pitch range-- of neutral and oriented interrogative utterances in the Spanish of Mexico City. We carried out a study of polar and wh- questions recorded in the free conversation module of the Corpus Norma Lingüística Culta (Lope Blanch 1971) and Habla Popular de la Ciudad de México (Lope Blanch 1976). The findings of the qualitative analysis show: i) the nuclear pitch configuration L* (L)H% --with the variants L* (L)H%, L* ¡H%, !H* ¡H%-- in information-seeking yes-no questions and confirmation questions, ii) the nuclear configuration L* L% documented in neutral wh- questions, and the boundary tone H% produced in the non-neutral condition --hypothetical or confirmative-- of the utterance; iii) the use of the pitch range as a potential prosodic resource for the expression of lesser or greater knowledge about the expected answer. The spontaneous speech data partially confirm the descriptions based on discourse completion tasks for this variety of Spanish (de-la-Mota et al. 2010). [ABSTRACT FROM AUTHOR]

HUMIC acid, COMPLEX matrices, XENOESTROGENS, POLLUTANTS, SEWAGE disposal plants, ENDOCRINE disruptors, and HUMUS

The presence of estrogenic endocrine disruptors in aquatic environments has been a concern and bioassays are recommended tools for their monitoring. However, the physicochemical properties of contaminants and the environmental matrix features may influence the resultant response. This study aimed to assess this influence on the Yeast Estrogen Screen (YES) assay. Mixtures of 17β-estradiol (E2) and humic acid (HA) were evaluated through the Schild approach aiming to investigate the interactions between estrogens and dissolved organic matter (DOM). Moreover, environmental samples from municipal landfill leachate and wastewater treatment plant (WWTP) influents and effluents were screened for (anti)estrogenic activity at both dissolved and particulate phases. Finally, results were statistically confronted with physicochemical parameters through principal component analysis (PCA). The HA test concentrations strongly reduced the E2 response, even at low levels. Humic substances may not only reduce estrogen bioavailability, but also interfere with the assay mechanism through enzymatic inhibition thus masking the sample estrogenic potential. Landfill leachate had total E2-Eq in the range 1282–2591 ng L−1, while WWTP influent and effluent were in the range 12.1–41.4 and L−1, so estrogenicity was reduced 92% in average. Particulate phase was responsible for 33–100% of measured E2-Eq between matrices, though cytotoxicity occurred in some extracts. Antiestrogenic activity was observed in both phases and might also have masked the estrogenicity of samples. PCA did not resulted in positive correlations supporting a multiphase distribution pattern of estrogenic compounds. Nevertheless, the solids and organic matter characteristics supported the data interpretation. In conclusion, the in vitro YES assay is subjected to factors intrinsic to the environmental sample that can influence on the measured estrogenic response. Therefore, results interpretation should be performed together with organic matter characterization parameters, cytotoxicity and antiestrogenic activity evaluation. [Display omitted] • Humic acid induces strong antagonistic effect in the Yeast Estrogen Screen. • Landfill leachate, WWTP influents and effluents were highly estrogenic. • Cytotoxicity was recurrently associated with particles >0.7 μm. • DOM, antiestrogenic activity and phase distribution influenced on estrogenic response. [ABSTRACT FROM AUTHOR]

KINASES, YAP signaling proteins, FIBROBLAST growth factor 2, FIBROBLAST growth factor receptors, HIPPO signaling pathway, DRUG toxicity, and CHOLANGIOCARCINOMA

There is an unmet need to develop novel, effective medical therapies for cholangiocarcinoma (CCA). The Hippo pathway effector, Yes-associated protein (YAP), is oncogenic in CCA, but has historically been difficult to target therapeutically. Recently, we described a novel role for the LCK proto-oncogene, Src family tyrosine kinase (LCK) in activating YAP through tyrosine phosphorylation. This led to the hypothesis that LCK is a viable therapeutic target in CCA via regulation of YAP activity. A novel tyrosine kinase inhibitor with relative selectivity for LCK, NTRC 0652-0, was pharmacodynamically profiled in vitro and in CCA cells. A panel of eight CCA patient-derived organoids were characterized and tested for sensitivity to NTRC 0652-0. Two patient-derived xenograft models bearing fibroblast growth factor receptor 2 (FGFR2)-rearrangements were utilized for in vivo assessment of pharmacokinetics, toxicity, and efficacy. NTRC 0652-0 demonstrated selectivity for LCK inhibition in vitro and in CCA cells. LCK inhibition with NTRC 0652-0 led to decreased tyrosine phosphorylation, nuclear localization, and co-transcriptional activity of YAP, and resulted in apoptotic cell death in CCA cell lines. A subset of tested patient-derived organoids demonstrated sensitivity to NTRC 0652-0. CCAs with FGFR2 fusions were identified as a potentially susceptible and clinically relevant genetic subset. In patient-derived xenograft models of FGFR2 fusion-positive CCA, daily oral treatment with NTRC 0652-0 resulted in stable plasma and tumor drug levels, acceptable toxicity, decreased YAP tyrosine phosphorylation, and significantly decreased tumor growth. A novel LCK inhibitor, NTRC 0652-0, inhibited YAP signaling and demonstrated preclinical efficacy in CCA cell lines, and patient-derived organoid and xenograft models. Although aberrant YAP activation is frequently seen in CCA, YAP targeted therapies are not yet clinically available. Herein we show that a novel LCK-selective tyrosine kinase inhibitor (NTRC 0652-0) effectively inhibits YAP tyrosine phosphorylation and cotranscriptional activity and is well tolerated and cytotoxic in multiple preclinical models. The data suggest this approach may be effective in CCA with YAP dependence or FGFR2 fusions, and these findings warrant further investigation in phase I clinical trials. [Display omitted] • LCK is a novel therapeutic target in cholangiocarcinoma. • Cholangiocarcinoma organoid and xenograft tumor models respond to LCK inhibition. • FGFR2-altered cholangiocarcinomas have enriched YAP activity and are sensitive to LCK inhibition. [ABSTRACT FROM AUTHOR]

Background: Soft tissue sarcoma is a rare but serious side-effect of radiotherapy to treat breast cancer, and rates are increasing in the USA. We evaluated potential co-factors in two complimentary cohorts of US breast cancer survivors.Methods: In this retrospective cohort study, we sourced data from the Kaiser Permanente (KP) cohort and the Surveillance, Epidemiology, and End Results (SEER) 13 registries cohort, both in the USA. The KP cohort included 15 940 women diagnosed with breast cancer from Jan 1, 1990, to Dec 31, 2016, in KP Colorado, KP Northwest (which serves Oregon and Southwest Washington state), or KP Washington, with detailed treatment data and comorbidities (including hypertension and diabetes at or before breast cancer diagnosis) from electronic medical records. The SEER cohort included 457 300 women diagnosed with breast cancer from Jan 1, 1992, to Dec 31, 2016, within the 13 SEER registries across the USA, with initial treatment data (yes vs no or unknown). Eligibility criteria in both cohorts were female breast cancer survivors (stage I-III) aged 20-84 years at diagnosis who had breast cancer surgery, and had survived at least 1 year after breast cancer diagnosis. The outcome of interest was any second thoracic soft tissue sarcoma (angiosarcomas and other subtypes) that developed at least 1 year after breast cancer diagnosis. Risk factors for thoracic soft tissue sarcoma were assessed using multivariable Poisson regression models.Findings: In the KP cohort, median follow-up was 9·3 years (IQR 5·7-13·9) and 19 (0·1%) of 15 940 eligible, evaluable women developed a thoracic soft tissue sarcoma (11 angiosarcomas, eight other subtypes). Most (94·7%; 18 of 19) thoracic soft tissue sarcomas occurred in women treated with radiotherapy; thus, radiotherapy was associated with a significantly increased risk of developing a thoracic soft tissue sarcoma (relative risk [RR] 8·1 [95% CI 1·1-60·4]; p=0·0052), but there was no association with prescribed dose, fractionation, or boost. The RR of angiosarcoma after anthracyclines was 3·6 (95% CI 1·0-13·3; p=0·058). Alkylating agents were associated with an increased risk of developing other sarcomas (RR 7·7 [95% CI 1·2-150·8]; p=0·026). History of hypertension (RR 4·8 [95% CI 1·3-17·6]; p=0·017) and diabetes (5·3 [1·4-20·8]; p=0·036) were each associated with around a five-times increased risk of angiosarcoma. In the SEER cohort, 430 (0·1%) of 457 300 patients had subsequent thoracic soft tissue sarcomas (268 angiosarcomas and 162 other subtypes) after a median follow-up of 8·3 years (IQR 4·3-13·9). Most (77·9%; 335 of 430) cases occurred after radiotherapy; thus, radiotherapy was associated with a significantly increased risk of developing a thoracic soft tissue sarcoma (RR 3·0 [95% CI 2·4-3·8]; p<0·0001) and, for angiosarcomas, the RR for breast-conserving surgery plus radiotherapy versus mastectomy plus radiotherapy was 1·9 (1·1-3·3; p=0·012). By 10 years after radiotherapy, the cumulative incidence of thoracic soft tissue sarcoma was 0·21% (95% CI 0·12-0·34) in the KP cohort and 0·15% (95% CI 0·13-0·17) in SEER.Interpretation: Radiotherapy was the strongest risk factor for thoracic soft tissue sarcoma in both cohorts. This finding, along with the novel findings for diabetes and hypertension as potential risk factors for angiosarcomas, warrant further investigation as potential targets for prevention strategies and increased surveillance.Funding: US National Cancer Institute and National Institutes of Health. [ABSTRACT FROM AUTHOR]

RADIATION exposure, MEDICAL personnel, COMPUTED tomography, RADIATION protection, and CLINICAL indications

Purpose: To obtain clinicians' views of the need to account for radiation exposure from previous CT scans and the advisability of a regulatory mechanism to control the number of CT scans for an individual patient.Methods: A convenience survey was conducted by emailing a link to a three-question electronic survey to clinicians in many countries, mostly through radiology and radiation protection contacts.Results: 505 responses were received from 24 countries. 293 respondents (58%) understand that current regulations do not limit the number of CT scans that can be prescribed for a single patient in a year. When asked whether there should be a regulation to limit the number of CT scans that can be prescribed for a single patient in one year, only a small fraction (143, 28%) answered 'No', 182 (36%) answered 'Maybe' and 166 (33%) answered 'Yes'. Most respondents (337; 67%) think that radiation risk should form part of the consideration when deciding whether to request a CT exam. A minority (138; 27%) think the decision should be based only on the medical indication for the CT exam. Comparison among the 4 countries (South Korea, Hungary, USA and Canada) with the largest number of respondents indicated wide variations in responses.Conclusions: A majority of the surveyed clinicians consider radiation risk, in addition to clinical factors, when prescribing CT exams. Most respondents are in favor of, or would consider, regulation to control the number of CT scans that could be performed on a patient annually. [ABSTRACT FROM AUTHOR]

TALAROMYCES, CACAO, FUNGAL growth, NATURAL resources, SOIL pollution, and SOILS

Inorganic pollutants in Colombian cocoa (Theobroma cacao L.) agrosystems cause problems in the production, quality, and exportation of this raw material worldwide. There has been an increased interest in bioprospecting studies of different fungal species focused on the biosorption of heavy metals. Furthermore, fungi constitute a valuable, profitable, ecological, and efficient natural soil resource that could be considered in the integrated management of cadmium mitigation. This study reports a new species of Talaromyces isolated from a cocoa soil sample collected in San Vicente de Chucurí, Colombia. T. santanderensis is featured by Lemon Yellow (R. Pl. IV) mycelium on CYA, mono-to-biverticillade conidiophores, and acerose phialides. T. santanderensis is distinguished from related species by its growth rate on CYAS and powdery textures on MEA, YES and OA, high acid production on CREA and smaller conidia. It is differentiated from T. lentulus by its growth rate on CYA medium at 37 °C without exudate production, its cream (R. PI. XVI) margin on MEA, and dense sporulation on YES and CYA. Phylogenetic analysis was performed using a polyphasic approach, including different phylogenetic analyses of combined and individual ITS, CaM, BenA, and RPB2 gene sequences that indicate that it is new to science and is named Talaromyces santanderensis sp. nov. This new species belongs to the Talaromyces section and is closely related to T. lentulus, T. soli, T. tumuli, and T. pratensis (inside the T. pinophilus species complex) in the inferred phylogeny. Mycelia growth of the fungal strains was subjected to a range of 0–400 mg/kg Cd and incorporated into malt extract agar (MEA) in triplicates. Fungal radial growth was recorded every three days over a 13-day incubation period and In vitro cadmium tolerance tests showed a high tolerance index (0.81) when the mycelium was exposed to 300 mg/kg of Cd. Results suggest that T. santanderensis showed tolerance to Cd concentrations that exceed the permissible limits for contaminated soils, and it is promising for its use in bioremediation strategies to eliminate Cd from highly contaminated agricultural soils. [ABSTRACT FROM AUTHOR]

AUTISM in children, AUTISTIC children, MEDICAL screening, AUTISM, COMMUNITIES, and TEACHING hospitals

The Indian Autism Screening Questionnaire (IASQ), derived from the Indian Scale for Assessment of Autism ISAA (the mandated tool for autism in India), is an autism screening instrument for use in the general population by minimally trained workers. While ISAA has 40 items with four anchor points, the IASQ is a 10-item questionnaire with yes/no answers. It was initially validated using the ISAA. During its development the ISAA was itself compared to the Childhood Autism Rating Scale version 1 (ISAA Manual). In the present study, we evaluated both the ISAA and the IASQ in relation to the Childhood Autism Rating Scale version 2 (CARS-2). Methods: Participants were recruited from three settings: a referral clinic for neurodevelopmental conditions run by the Department of Paediatrics of a tertiary care teaching hospital (NDC OPD), the outpatient department of an institute for disability and rehabilitation (NIEPID), and from the community (CGOC). Persons between ages 3–18 were recruited following consent or assent (parent and child/adolescent). The IASQ was administered by a minimally trained administrator. It was followed by ISAA and the CARS-2 (in alternating order, by different evaluators blind to each other) (CARS2 SV (Standard Version) and CARS2 HF (High Functioning) as applicable). Sensitivity, specificity and area under the Receiver Operator Characteristics (ROC) curve were calculated for IASQ and CARS2, as well as for ISAA and CARS2. Concordance between CARS2 and ISAA was calculated using kappa coefficient. Results: A total of 285 participants (NIEPD n = 124; NDC OPD, n = 4; CGOC n = 157) (a total of 70 with autism and 215 controls) participated. IASQ and CARS2 were administered on 285 participants, while IASQ and ISAA were administered on 264 participants. When IASQ was compared to CARS2, sensitivity was 97%, specificity 81%, PPV 63%, NPV 99% at cut off 1 while these values were 97%, 92%, 79% and 99% respectively at cut off 2. There was high concordance between CARS2 and ISAA (Kappa 0.907, p<0.0001). Conclusions: IASQ has satisfactory sensitivity, specificity and concordance when compared with CARS2; it can be used for screening children with autism in community. The ISAA also showed a high concordance with CARS2, as it had with the older version of CARS. [ABSTRACT FROM AUTHOR]

The contamination of water sources by pharmaceutically active compounds (PhACs) and their effect on aquatic communities and human health have become an environmental concern worldwide. Membrane bioreactors (MBRs) are an alternative to improve biological removal of recalcitrant organic compounds from municipal sewage. Their efficiency can be increased by using high retention membranes such as forward osmosis (FO) and membrane distillation (MD). Thus, this research aimed to evaluate the performance of an anaerobic osmotic MBR coupled with MD (OMBR-MD) in the treatment of municipal sewage containing PhACs and estrogenic activity. A submerged hybrid FO-MD module was integrated into the bioreactor. PhACs removal was higher than 96% due to biological degradation, biosorption and membrane retention. Biological removal of the PhACs was affected by the salinity build-up in the bioreactor, with reduction in biodegradation after 32 d. However, salinity increment had little or no effect on biosorption removal. The anaerobic OMBR-MD removed >99.9% of estrogenic activity, resulting in a distillate with 0.14 ng L−1 E2-eq, after 22 d, and 0.04 ng L−1 E2-eq, after 32 d. OMBR-MD treatment promoted reduction in environmental and human health risks from high to low, except for ketoprofen, which led to medium acute environmental and human health risks. Carcinogenic risks were reduced from unacceptable to negligible, regarding estrogenic activity. Thus, the hybrid anaerobic OMBR-MD demonstrated strong performance in reducing risks, even when human health is considered. [Display omitted] • Biological removal of estrogenic compounds was governed mainly by biodegradation. • Biological removal of micropollutants (MP) was affected by the salinity build-up. • MgCl 2 as draw solute reduced the negative impacts on biological removal of MP. • Ketoprofen in distillate led to medium acute environmental and human health risks. • Carcinogenic risk, regarding estrogenicity, reduced from unacceptable to negligible. [ABSTRACT FROM AUTHOR]

DRUG discovery, DATA mining, and CHEMINFORMATICS