Preoperative word-finding difficulties in children with posterior fossa tumours: a European cross-sectional study.

PURPOSE: Posterior fossa tumour surgery in children entails a high risk for severe speech and language impairments, but few studies have investigated the effect of the tumour on language prior to surgery. The current crosslinguistic study addresses this gap. We investigated the prevalence of preoperative word-finding difficulties, examined associations with medical and demographic characteristics, and analysed lexical errors. METHODS: We included 148 children aged 5-17 years with a posterior fossa tumour. Word-finding ability was assessed by means of a picture-naming test, Wordrace, and difficulties in accuracy and speed were identified by cut-off values. A norm-based subanalysis evaluated performance in a Swedish subsample. We compared the demographic and medical characteristics of children with slow, inaccurate, or combined slow and inaccurate word finding to the characteristics of children without word-finding difficulties and conducted a lexical error analysis. RESULTS: Thirty-seven percent (n = 55) presented with slow word finding, 24% (n = 35) with inaccurate word finding, and 16% (n = 23) with both slow and inaccurate word finding. Children with posterior fossa tumours were twice as slow as children in the norming sample. Right-hemisphere and brainstem location posed a higher risk for preoperative word-finding difficulties, relative to left-hemisphere location, and difficulties were more prevalent in boys than in girls. The most frequent errors were lack of response and semantically related sideordinated words. CONCLUSION: Word-finding difficulties are frequent in children with posterior fossa tumours, especially in boys and in children with right-hemisphere and brainstem tumours. Errors resemble those observed in typical development and children with word-finding difficulties.

Preliminary report of intraovarian injections of autologous platelet-rich plasma (PRP) in extremely poor prognosis patients with only oocyte donation as alternative: a prospective cohort study.

STUDY QUESTION: Does intraovarian injection of platelet-rich plasma (PRP) change ovarian function in patients with extremely low functional ovarian reserve (LFOR) who, otherwise, would likely only have a chance of pregnancy through third-party oocyte donation? SUMMARY ANSWER: No clinically significant effects of PRP treatment on ovarian function were observed over 1 year of follow-up. WHAT IS KNOWN ALREADY: Several investigators have reported improved responses to ovulation induction after treatment with PRP. However, previous published reports have involved, at most, only small case series. Whether PRP actually improves ovarian performance is, therefore, still unknown. PRP is nevertheless widely offered as an 'established' fertility treatment, often under the term 'ovarian rejuvenation'. STUDY DESIGN SIZE DURATION: We are reporting a prospective cohort study of 80 consecutive patients at ages 28-54 with LFOR, defined by anti-Müllerian hormone <1.1 ng/ml, FSH >12 mIU/ml or at least one prior IVF cycle with ≤3 oocytes within 1 year. The women were followed for 1 year after an intraovarian PRP procedure. PARTICIPANTS/MATERIALS SETTING METHODS: PRP (1.5 ml) was injected into the cortex of ovaries with an average of 12 injections per ovary. Study participants were followed every 3 days for 2 weeks after PRP treatment with estradiol and FSH measurements and vaginal ultrasound to observe follicle growth and thereafter followed weekly. Beginning 1 month after their PRP treatment, participants underwent one or more cycles of ovarian stimulation for IVF. Outcome measures were endocrine response, and numbers of oocytes and embryos produced in response to a maximal gonadotropin stimulation before and after PRP treatment. MAIN RESULTS AND THE ROLE OF CHANCE: In this study, women failed to demonstrate statistically significant outcome benefits from intraovarian PRP. However, two 40-year-old very poor-prognosis patients, with prior failed IVF cycles that never reached embryo transfer at other centers, achieved pregnancy, resulting in an ongoing pregnancy rate of 4.7% among patients who, following PRP, produced at least one oocyte (n = 42). LIMITATIONS REASONS FOR CAUTION: As an observational study of patients who performed poorly in past ovarian stimulation cycles, the improvement may be accounted for by regression to the mean. Similar considerations may also explain the occurrence of the two pregnancies. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrates that, even in extremely poor prognosis patients due to LFOR, sporadic pregnancies are possible. The study, however, does not allow for the conclusion that those pregnancies were the consequence of PRP treatments. A case series, indeed, does not allow for such conclusions, even if results are more suggestive than here. This registered study, therefore, must be viewed as a preliminary report, with further data expected from this study but also from two other prospectively randomized ongoing registered studies with more controlled patient selection. STUDY FUNDING/COMPETING INTERESTS: This work was supported by intramural funds from The Center for Human Reproduction and the not-for-profit research Foundation for Reproductive Medicine, both in New York, NY, USA. N.G. and D.H.B. are listed as co-inventors on several US patents. Some of these patents relate to pre-supplementation of hypo-androgenic infertile women with androgens, such as dehydroepiandrosterone and testosterone and, therefore, at least peripherally relate to the subject of this manuscript. They, as well as D.F.A., have also received research support, travel funds and speaker honoraria from several pharmaceutical and medical device companies, though none related to the here presented subject and manuscript. N.G. is a shareholder in Fertility Nutraceuticals and he and D.H.B. receive royalty payments from Fertility Nutraceuticals LLC. E.M. has no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NCT04275700.

IVF outcomes of embryos with abnormal PGT-A biopsy previously refused transfer: a prospective cohort study.

STUDY QUESTION: What are the outcomes for patients who choose to move embryos diagnosed as abnormal by preimplantation genetic testing for aneuploidy (PGT-A) to a new institution for transfer after the diagnosing institution refused to transfer them? SUMMARY ANSWER: Many patients seek to have selected embryos with PGT-A abnormal trophectoderm biopsies transferred recognizing that these embryos can still offer a chance of pregnancy and live birth. WHAT IS KNOWN ALREADY: : PGT-A is a widely practiced method of selecting embryos for transfer based on biopsy of a few cells. Many clinical practices refuse to transfer PGT-A abnormal embryos even when there are no other 'normal' embryos available. STUDY DESIGN, SIZE, DURATION: This is a prospective cohort of 69 couples who, since 2014, moved a total of 444 PGT-A abnormal embryos previously refused transfer at their parent institutions to our practice. Among these, 50 patients have, thus far, undergone 57 transfer cycles of 141 embryos. PARTICIPANTS/MATERIALS, SETTING, METHODS: Embryos diagnosed at other institutions by PGT-A as abnormal (mostly using next generation sequencing) were moved to our academically affiliated private fertility and research center in New York City. Female age at retrieval was 41.35 ± 3.98 years, 74% were Caucasian, 12% Asian and 10% were of African descent. All embryos identified as PGT-A abnormal among prospectively identified couples were recorded in our center's registry. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 144 embryos transferred 102 (72.3%) had only 1 or 2 chromosomal abnormalities, 30 (21.3%) had 3 or more and 9 (6.4%) were 'undiagnosed' because of degraded DNA, yet still had been refused transfer. Transfer of PGT-A abnormal embryos resulted in 8 live births, 11 miscarriages and no voluntary terminations. One child was born with a segmental duplication and required repair of coarctation of the aorta as a newborn. Many couples with only PGT-A abnormal embryos are willing to have their PGT-A abnormal embryos transferred and such transfers can result in the establishment of ongoing euploid pregnancies and live births. LIMITATIONS, REASONS FOR CAUTION: Findings in this case series represent couples who chose to have their embryos transferred after having been refused transfer elsewhere and may not be representative of the wider population of couples undergoing IVF with PGT-A in general. Not all abnormal phenotypes present in the immediate postnatal period so it will be important to continue to follow the development of these children. WIDER IMPLICATIONS OF THE FINDINGS: PGT-A can result in a clinics refusal to transfer embryos with abnormal PGT-A biopsies, even those with mosaic findings, consequently large numbers of infertile women are prematurely advised that their only chance of motherhood is through third-party egg-donation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by intramural funds from the Center for Human Reproduction and the not-for-profit research Foundation for Reproductive Medicine, both in New York, NY, USA. N.G. and D.H.B. are listed as co-inventors on several U.S. patents. One of these patents (US Patent# 7,615,544) relates to pre-supplementation of hypo-androgenic infertile women with androgens, such as DHEA and testosterone and, therefore, at least peripherally related to the subject of this manuscript. N.G. and D.F.A. also received travel funds and speaker honoraria from several pharmaceutical and medical device companies, though none related to the here presented subject and manuscript. N.G. is a shareholder in Fertility Nutraceuticals and he and D.H.B. receive royalty payments from Fertility Nutraceuticals LLC. TRIAL REGISTRATION NUMBER: N/A.

The "common" experience of voice-hearing and its relationship with shame and guilt: a systematic review.

BACKGROUND: Despite Auditory Verbal Hallucinations (AVHs) having been long associated with mental illness, they represent a common experience also in the non-clinical population, yet do not exhibit distress or need for care. Shame and guilt are emotions related to one's perception of oneself and one's responsibility. As such, they direct our attention to aspects of AVHs that are under-researched and elusive, particularly about the status of voices as others, their social implications and the constitution and conceptualisation of the self. OBJECTIVES: This paper aims to provide a systematic review of studies that investigated the relationship between auditory hallucinations, shame, and guilt in people without relevant signs of psychiatric issues. METHODS: We searched studies reporting information about voices characteristics, the relationship between voices and hearers, hearer's reactions, and beliefs, paying peculiar attention to shame and guilt issues. Included papers were evaluated for risk of bias. RESULTS: Eleven studies that explored the relationship between AVHs, shame and guilt, were extracted. Phenomenological, pragmatic, as well as neuropsychological features of hearing voices in non-clinical populations, allowed us to note a dynamic relationship and the constellation of subjective experiences that can occur. The role of guilt was characterized by few studies and mixed results, while shame was mainly common. CONCLUSIONS: Due to the high heterogeneity detected and the scarce sources available, further studies should focus on both the aetiology and the bidirectional relationship between hearing voices, shame, and guilt in non-clinical people. This can be helpful in therapies for non-clinical populations who are distressed by their voices (e.g., psychotherapy), and for whom shame, and guilt may contribute to negative consequences such as isolation, anxiety or future depression. Moreover, it might favour the development and implication of different treatments considering emotion regulation, distress tolerance and interpersonal sensitivity on the clinical populations.

Postoperative speech impairment and cranial nerve deficits after secondary surgery of posterior fossa tumours in childhood: a prospective European multicentre study.

PURPOSE: Brain tumours constitute 25% of childhood neoplasms, and half of them are in the posterior fossa. Surgery is a fundamental component of therapy, because gross total resection is associated with a higher progression-free survival. Patients with residual tumour, progression of residual tumour or disease recurrence commonly require secondary surgery. We prospectively investigated the risk of postoperative speech impairment (POSI) and cranial nerve dysfunction (CND) following primary and secondary resection for posterior cranial fossa tumours. METHODS: In the Nordic-European study of the cerebellar mutism syndrome, we prospectively included children undergoing posterior fossa tumour resection or open biopsy in one of the 26 participating European centres. Neurological status was assessed preoperatively, and surgical details were noted post-operatively. Patients were followed up 2 weeks, 2 months and 1 year postoperatively. Here, we analyse the risk of postoperative speech impairment (POSI), defined as either mutism or reduced speech, and cranial nerve dysfunction (CND) following secondary, as compared to primary, surgery. RESULTS: We analysed 426 children undergoing primary and 78 undergoing secondary surgery between 2014 and 2020. The incidence of POSI was significantly lower after secondary (12%) compared with primary (28%, p = 0.0084) surgery. In a multivariate analysis adjusting for tumour histology, the odds ratio for developing POSI after secondary surgery was 0.23, compared with primary surgery (95% confidence interval: 0.08-0.65, p = 0.006). The frequency of postoperative CND did not differ significantly after primary vs. secondary surgery (p = 0.21). CONCLUSION: Children have a lower risk of POSI after secondary than after primary surgery for posterior fossa tumours but remain at significant risk of both POSI and CND. The present findings should be taken in account when weighing risks and benefits of secondary surgery for posterior fossa tumours.

Expression patterns of ciliopathy genes ARL3 and CEP120 reveal roles in multisystem development.

BACKGROUND: Joubert syndrome and related disorders (JSRD) and Jeune syndrome are multisystem ciliopathy disorders with overlapping phenotypes. There are a growing number of genetic causes for these rare syndromes, including the recently described genes ARL3 and CEP120. METHODS: We sought to explore the developmental expression patterns of ARL3 and CEP120 in humans to gain additional understanding of these genetic conditions. We used an RNA in situ detection technique called RNAscope to characterise ARL3 and CEP120 expression patterns in human embryos and foetuses in collaboration with the MRC-Wellcome Trust Human Developmental Biology Resource. RESULTS: Both ARL3 and CEP120 are expressed in early human brain development, including the cerebellum and in the developing retina and kidney, consistent with the clinical phenotypes seen with pathogenic variants in these genes. CONCLUSIONS: This study provides insights into the potential pathogenesis of JSRD by uncovering the spatial expression of two JSRD-causative genes during normal human development.

Technologically-enhanced psychological interventions for older adults: a scoping review.

BACKGROUND: The world population is getting older. As life expectancy increases, traditional health care systems are facing different challenges in terms of cost reduction and high-quality service delivery capability. New ways to improve older adults' quality of life have been explored, taking advantage of new technological solutions. Our focus is on the integration of technology in clinical treatments to facilitate or deliver psychological interventions meant to improve well-being in older adults. Our aims were to describe the main technology-based interventions supporting seniors' quality of life or psychological well-being and to provide greater clarity to what is described in the current literature as their effects on seniors' cognitive and psychological outcomes and healthcare policies. METHODS: We reviewed the scientific literature looking for studies that investigated how technology can be implemented into clinical psychology treatments for older adults. Our search was conducted using the following databases: PubMed, PsycINFO, Scopus, ISI Web of Science, and CINAHL. The search provided 350 articles, mostly (≈90%) dated after 2002. Abstract analysis narrowed the selection to 150 papers, according to their relevance and actuality as judged by a restricted group of independent researchers. RESULTS: Through a thematic analysis, we found that virtual reality (VR), robots, telemedicine, software, video games, and smartphone applications could potentially support older adults' psychological treatment with a positive impact on healthcare systems. CONCLUSION: Findings from the literature are encouraging, although most of these results are only preliminary.

Embryonic and foetal expression patterns of the ciliopathy gene CEP164.

Nephronophthisis-related ciliopathies (NPHP-RC) are a group of inherited genetic disorders that share a defect in the formation, maintenance or functioning of the primary cilium complex, causing progressive cystic kidney disease and other clinical manifestations. Mutations in centrosomal protein 164 kDa (CEP164), also known as NPHP15, have been identified as a cause of NPHP-RC. Here we have utilised the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR) to perform immunohistochemistry studies on human embryonic and foetal tissues to determine the expression patterns of CEP164 during development. Notably expression is widespread, yet defined, in multiple organs including the kidney, retina and cerebellum. Murine studies demonstrated an almost identical Cep164 expression pattern. Taken together, these data support a conserved role for CEP164 throughout the development of numerous organs, which, we suggest, accounts for the multi-system disease phenotype of CEP164-mediated NPHP-RC.

Broadband near-infrared astronomical spectrometer calibration and on-sky validation with an electro-optic laser frequency comb.

The quest for extrasolar planets and their characterization as well as studies of fundamental physics on cosmological scales rely on capabilities of high-resolution astronomical spectroscopy. A central requirement is a precise wavelength calibration of astronomical spectrographs allowing for extraction of subtle wavelength shifts from the spectra of stars and quasars. Here, we present an all-fiber, 400 nm wide near-infrared frequency comb based on electro-optic modulation with 14.5 GHz comb line spacing. Tests on the high-resolution, near-infrared spectrometer GIANO-B show a photon-noise limited calibration precision of < 10 cms as required for Earth-like planet detection. Moreover, the presented comb provides detailed insight into particularities of the spectrograph such as detector inhomogeneities and differential spectrograph drifts. The system is validated in on-sky observations of a radial velocity standard star (HD221354) and telluric atmospheric absorption features. The advantages of the system include simplicity, robustness and turn-key operation, features that are valuable at the observation sites.

Meditation training for people with amyotrophic lateral sclerosis: a randomized clinical trial.

BACKGROUND AND PURPOSE: Studies investigating psychological interventions for the promotion of well-being in people with amyotrophic lateral sclerosis (ALS) are lacking. The purpose of the current study was to examine the use of an ALS-specific mindfulness-based intervention for improving quality of life in this population. METHODS: A randomized, open-label and controlled clinical trial was conducted on the efficacy of an ALS-specific meditation programme in promoting quality of life. Adults who received a diagnosis of ALS within 18 months were randomly assigned either to usual care or to an 8-week meditation training based on the original mindfulness-based stress reduction programme and tailored for people with ALS. Quality of life, assessed with the ALS-Specific Quality of Life Revised scale, represented the primary outcome, whilst secondary outcomes included anxiety and depression, assessed with the Hospital Anxiety and Depression Scale, and specific quality of life domains. Participants were assessed at recruitment and after 2, 6 and 12 months. The efficacy of the treatment was assessed on an intention-to-treat basis of a linear mixed model. RESULTS: A hundred participants were recruited between November 2012 and December 2014. Over time, there was a significant difference between the two groups in terms of quality of life (ß = 0.24, P = 0.015, d = 0.89). Significant differences between groups over time were also found for anxiety, depression, negative emotions, and interaction with people and the environment. CONCLUSIONS: An ALS-specific meditation programme is beneficial for the quality of life and psychological well-being of people with ALS.

Transcriptome analysis of human cumulus cells reveals hypoxia as the main determinant of follicular senescence.

STUDY QUESTION: Can RNA sequencing of human cumulus cells (CC) reveal molecular pathways involved in the physiology of reproductive aging? STUDY FINDING: Senescent but not young CC activate gene pathways associated with hypoxia and oxidative stress. WHAT IS KNOWN ALREADY: Shifts in socioeconomic norms are resulting in larger numbers of women postponing childbearing. The reproductive potential is sharply decreased with aging, and the reasons are poorly understood. Since CCs play an integral role in oocyte maturation and direct access to human oocytes is limited, we used whole transcriptome analysis of these somatic cells to gain insights into the molecular mechanisms playing a role in follicular senescence. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Twenty CC samples (from a total of 15 patients) were obtained from oocytes of either male factor or egg donor patients. RNA sequencing and bioinformatic tools were used to identify differentially expressed genes between CCs from seven aged and eight young patients (<35 (years old) y.o. vs >40 y.o.). Quantitative-PCR and immunoflourescent staining were used for validation. MAIN RESULTS AND THE ROLE OF CHANCE: RNA sequencing identified 11 572 genes expressed in CC of both age cohorts, 45 of which were differentially expressed. In CC collected from patients >40 y.o., genes involved in the hypoxia stress response (NOS2, RORA and NR4A3), vasculature development (NR2F2, PTHLH), glycolysis (RALGAPA2 and TBC1D4) and cAMP turnover (PDE4D) were significantly overexpressed when compared with CC of patients younger than 35 y.o. LIMITATIONS, REASONS FOR CAUTION: This study focused almost exclusively on assessing the genetic differences in CC transcriptome between young and older women. These genetic findings were not fully correlated with embryonic development and clinical outcome. WIDER IMPLICATIONS OF THE FINDINGS: Our data provide a new hypothesis-follicular hypoxia-as the main mechanism leading to ovarian follicular senescence and suggest a link between cumulus cell aging and oocyte quality decay. If specific molecular findings of hypoxia would be confirmed also in oocytes, genetic platforms could screen CC for hypoxic damage and identify healthier oocytes. Protocols of ovarian stimulation in older patients could also be adjusted to diminish oocyte exposure time to hypoxic follicles. LARGE SCALE DATA: GEO accession number: GSE81579 STUDY FUNDING AND COMPETING INTERESTS: Funded in part by EMD Serono Grant for Fertility Innovation (GFI).

Age and comorbidities deeply impact on clinical outcome of patients with myelodysplastic syndromes.

BACKGROUND: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders, with very different prognosis in given individuals; age and comorbidities are emerging as relevant patient-related factors influencing clinical outcome in MDS. Our aim was to evaluate the impact of age, comorbidities and disease severity (IPSS and IPSS-R prognostic scores) in a "real-life" series of MDS patients. METHODS: 318 patients with available assessment of comorbidities at diagnosis and consecutively registered into the Registro Ligure delle Mielodisplasie were analyzed. Comorbidities were evaluated according to HCT-CI and MDS-CI comorbidity indexes. Overall survival (OS) and the probability of death among patients who did not develop acute myeloid leukemia (NLD cumulative incidence) were analyzed. RESULTS: Comorbidities were seen in 177 (55.7%) patients. An older age (>75 y) had a significant negative impact on OS (p=0.008). HCT-CI was not associated with OS. MDS-CI was of prognostic significance (p=0.001), but the association was limited to pts with IPSS or IPSS-R "lower-risk". In multivariate analysis, MDS-CI remained an independent factor associated with OS and with an increased risk of NLD both when controlling for IPSS (p=0.019 and p=0.001, respectively) and for IPSS-R (p=0.048 and p=0.002, respectively). CONCLUSIONS: Evaluation of age and comorbidities according to a tailored tool such is MDS-CI helps to predict survival in patients with MDS and should be incorporated to current prognostic scores.

A standardised tool for assessing needs in forensic psychiatric population: clinical validation of the Italian CANFOR, staff version.

BACKGROUND: The Camberwell Assessment of Need - Forensic Version (CANFOR) is a standardised assessment tool specifically designed to assess needs for care in forensic psychiatric populations. The original English version of the instrument has shown good psychometric properties. The aim of this study was to validate the Italian version of the CANFOR-staff tool. METHOD: After translation and back-translation, the Italian CANFOR tool was administered to a sample of 50 forensic psychiatric patients. Convergent validity was tested using the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment of Functioning (GAF) by applying Kendall's tau-b. Inter-rater and test-retest reliabilities were measured by ICCs for need dimensions (total and unmet) and Cohen's kappa coefficients for individual need items. RESULTS: Regarding convergent validity, a higher number of needs (total and unmet) were associated with more severe psychiatric symptoms (BPRS). Higher numbers of unmet needs were also associated with lower levels of global functioning (GAF). ICCs for total and unmet needs scores indicated a good level of agreement for inter-rater reliability and a very good level for test-retest, respectively. Regarding the specific items, inter-rater Cohen's kappa was high (moderate to very good agreement) for 18 items in relation to the presence of a need and for 15 items in the rating of an unmet need, whereas Cohen's kappa for test-retest reliability was very high for all the items in the presence of a need and high for 18 of the unmet need domains. CONCLUSIONS: The Italian version of CANFOR has adequate psychometric properties. It can be considered a promising instrument for the assessment of needs of forensic psychiatric patients.

Concurrent comparison of the measurement properties of generic and disease-specific questionnaires in obese inpatients.

BACKGROUND: The concurrent comparison of questionnaires assessing health-related quality of life in the same population is necessary for better appreciating their performance and to select the best instrument for a given purpose (e.g. clinical trials and observational studies). AIM: The aim of this study was to compare the measurement properties of two disease-specific and generic questionnaires: the Obesity-related Well-Being (ORWELL97), the Obesity-Related Disability test (TSD-OC), the EuroQoL, and the World Health Organization Quality of Life questionnaire. MATERIALS/SUBJECTS: Two-hundreds and forty-nine obese inpatients [age 47 (standard deviation, SD 15) years, body mass index 44.4 (SD 5.2) kg/m(2), 69 % female] completed the four questionnaires before and after a 3-week multidisciplinary weight reduction program. Standard measurement properties were calculated and compared. RESULTS: Intra-class correlation coefficient ranged from 0.73 to 0.90 for most of the instruments and subscales. The standard error of measurement ranged from 9 to 21 % for the generic instruments, and from 9 to 44 % for the specific questionnaires. Missing data and ceiling effects were found for TSD-OC. Responsiveness was similar for all the instruments. The correlations between the change scores of the instruments were small (<0.37). CONCLUSIONS: It was not possible to identify a "best" instrument, but overall the ORWELL97 seems to show better measurement properties. The two specific instruments measured different constructs and they did not show a clear superior performance compared to the generic questionnaires.

Role of fistulography in evaluating pancreatic fistula after pancreaticoduodenectomy.

OBJECTIVE: To evaluate the usefulness of fistulography as a diagnostic and management tool for clinically suspected pancreatic fistulas (PF) after pancreaticoduodenectomy (PD). METHODS: 84 consecutive fistulographies were performed for clinical suspicion of PF and retrospectively analysed. We radiologically defined two types of PF by means of fistulography, PF1 in the case of primary filling with contrast agent of the jejunal loop or stomach and PF2 in the case of secondary filling of the jejunal loop or stomach through a fistulous tract or a fluid collection. RESULTS: In 35/84 (41.7%) of the fistulograms, a PF1 was demonstrated owing to an instantaneous opacification of the intestinal lumen or the stomach, without evidence of a fistulous tract or fluid collection. In 49/84 (58.3%) fistulograms, a PF2 was demonstrated by the depiction of a fluid collection and/or a fistulous tract and a communication with the intestinal loop or the stomach anastomised with the pancreas. The mean healing time of a PF after PD was 2.7 days for PF1, and 9.8 days for PF2. CONCLUSION: Fistulography helps in the confirmation of clinically suspect PF, and can distinguish PF1 and PF2, thus decreasing post-operative morbidity significantly.

GRB 090423 at a redshift of z approximately 8.1.

Gamma-ray bursts (GRBs) are produced by rare types of massive stellar explosion. Their rapidly fading afterglows are often bright enough at optical wavelengths that they are detectable at cosmological distances. Hitherto, the highest known redshift for a GRB was z = 6.7 (ref. 1), for GRB 080913, and for a galaxy was z = 6.96 (ref. 2). Here we report observations of GRB 090423 and the near-infrared spectroscopic measurement of its redshift, z = 8.1(-0.3)(+0.1). This burst happened when the Universe was only about 4 per cent of its current age. Its properties are similar to those of GRBs observed at low/intermediate redshifts, suggesting that the mechanisms and progenitors that gave rise to this burst about 600,000,000 years after the Big Bang are not markedly different from those producing GRBs about 10,000,000,000 years later.

GolP: an atomistic force-field to describe the interaction of proteins with Au(111) surfaces in water.

A classical atomistic force field to describe the interaction of proteins with gold (111) surfaces in explicit water has been devised. The force field is specifically designed to be easily usable in most common bio-oriented molecular dynamics codes, such as GROMACS and NAMD. Its parametrization is based on quantum mechanical (density functional theory [DFT] and second order Möller-Plesset perturbation theory [MP2]) calculations and experimental data on the adsorption of small molecules on gold. In particular, a systematic DFT survey of the interaction between Au(111) and the natural amino acid side chains has been performed to single out chemisorption effects. Van der Waals parameters have been instead fitted to experimental desorption energy data of linear alkanes and were also studied via MP2 calculations. Finally, gold polarization (image charge effects) is taken into account by a recently proposed procedure (Iori, F.; Corni, S. J Comp Chem 2008, 29, 1656). Preliminary validation results of GolP on an independent test set of small molecules show the good performances of the force field.

[Towards a multi-step informed consent: considerations and proposals for a good practice]. / Verso un consenso informato a più fasi: considerazioni e proposte per una buona prassi.

Any therapeutic intervention needs consent from the patient, after have received information from the physician. This is often seen as a bureaucratic accomplishment but it could enhance therapeutic alliance. We propose to divide consent from information, offering a place in which doubts and emotions can be explored, with the assistance of a psychological interview. We believe that this new approach can enhance physician-patient relationship, with an improvement in patient satisfaction and a decrease of claims and complaints.

D2 dopamine receptor (DRD2) gene Taq1A polymorphism and the eating-related psychological traits in eating disorders (anorexia nervosa and bulimia) and obesity.

OBJECTIVE: Food is considered a reinforcing agent, like a variety of substances such as alcohol and other drugs of abuse that produce pleasure. Psychopathological traits related to food intake are demonstrated in eating disorders as in obesity with different genetic aspects for these diseases. Recently, the prevalence of TaqA1 allele has been associated to alcohol, drug abuse and carbohydrate preference. For this reason, the aim of this study was to evaluate if the presence of A1 allele, in eating disorders and obesity, is associated with some particular psycho-pathological characteristics. METHODS: We studied the presence of TaqA1 in Italian subjects affected by obesity (n=71), anorexia (n=28), bulimia (n=20) and in control group (n=54). The Eating Disorders Inventory (EDI test) was used to evaluate the psychological profiles. Patients without alcohol and drugs abuse were selected (>125 ml/day). RESULTS: The A1+ allele, both in A1/A1 and A1/A2 genotypes, was not differently distributed among disease groups; on the contrary two EDI subscales (Drive for thinness and Ineffectiveness) resulted associated with A1+ allele without effect of the eating disease or obesity. CONCLUSION: These results confirm that the presence of A1+ allele is not simply related to body weight but the A1+ allele might be a marker of a genetic psychological condition in people with high risk to develop pathological eating behaviour.

Kinetics of in vivo bone deposition by bone marrow stromal cells within a resorbable porous calcium phosphate scaffold: an X-ray computed microtomography study.

Resorbable ceramic scaffolds based on Silicon stabilized tricalcium phosphate (Si-TCP) were seeded with bone marrow stromal cells (BMSC) and ectopically implanted for 2, 4, and 6 months in immunodeficient mice. Qualitative and quantitative evaluation of the scaffold material was performed by X-ray synchrotron radiation computed microtomography (microCT) with a spatial resolution lower than 5 microm. Unique to these experiments was that microCT data were first collected on the scaffolds before implantation and then on the same scaffolds after they were seeded with BMSC, implanted in the mice and rescued after different times. Volume fraction, mean thickness and thickness distribution were evaluated for both new bone and scaffold phases as a function of the implantation time. New bone thickness increased from week 8 to week 16. Data for the implanted scaffolds were compared with those derived from the analysis of the same scaffolds prior to implantation and with data derived from 100% hydroxyapatite (HA) scaffold treated and analyzed in the same way. At variance with findings with the 100% HA scaffolds a significant variation in the density of the different Si-TCP scaffold regions in the pre- and post-implantation samples was observed. In particular a post-implantation decrease in the density of the scaffolds, together with major changes in the scaffold phase composition, was noticeable in areas adjacent to newly formed bone. Histology confirmed a better integration between new bone and scaffold in the Si-TCP composites in comparison to 100% HA composites where new bone and scaffold phases remained well distinct.