Search

Many heritage speakers in diaspora communities are multilingual individuals, often speaking two or more heritage languages alongside the societal majority language as well as another lingua franca (i.e. English). This paper examines the multilingual practices of 26 Filipino speakers in Italy (15 from the first generation and 11 second generation) in the framework of Family Language Policy. Four main findings emerge from the sociolinguistic interviews: (1) the multilingualism of the first generation is reduced in second generation, with Philippine regional languages seldom transmitted to children; this is reflected in a varied attitude toward these languages; (2) in parent–children interactions the mixing of Filipino and Italian prevails, thus, although Italian is present, Filipino is always maintained, confirming an overall positive attitude; (3) English is never selected as the only language of communication, but rather in combination with Italian or Filipino; (4) in the second generation, the exclusive use of Italian occurs with peers or younger interlocutors (e.g. siblings, partners, children). This study further contributes to our understanding of linguistic choices among multilingual migrants by allowing a comparison with other Filipino diasporic communities in Asia, North America and Australia. [ABSTRACT FROM AUTHOR]

Simple Summary: In patients with locally advanced cervical cancer, the availability of imaging techniques for accurately defining the residual tumor would be clinically relevant for selecting patients who could be offered a more tailored surgery. The novelty of this prospective study is the development of multiparametric predictive models of histopathological response using a unique data set with three imaging modalities (transvaginal ultrasound, magnetic resonance (MRI) and 18F-FDG-PET/CT) evaluated at three time points ("baseline", two ("early") and five ("final") weeks after treatment). In a cohort of 88 patients, the predictive models retrieved integrating morphometric, vascular, perfusion and metabolic parameters, demonstrated that two imaging approaches (MRI and PET/CT at "final" evaluation or PET/CT at "baseline" and "final" evaluation) are sufficient to identify possible residual disease after chemotherapy. These findings could be useful in selecting patients with residual disease, helping clinicians to tailor the radicality of the surgical approach. Purpose: This study aimed to develop predictive models for pathological residual disease after neoadjuvant chemoradiation (CRT) in locally advanced cervical cancer (LACC) by integrating parameters derived from transvaginal ultrasound, MRI and PET/CT imaging at different time points and time intervals. Methods: Patients with histologically proven LACC, stage IB2–IVA, were prospectively enrolled. For each patient, the three examinations were performed before, 2 and 5 weeks after treatment ("baseline", "early" and "final", respectively). Multivariable logistic regression models to predict complete vs. partial pathological response (pR) were developed and a cost analysis was performed. Results: Between October 2010 and June 2014, 88 patients were included. Complete or partial pR was found in 45.5% and 54.5% of patients, respectively. The two most clinically useful models in pR prediction were (1) using percentage variation of SUVmax retrieved at PET/CT "baseline" and "final" examination, and (2) including high DWI signal intensity (SI) plus, ADC, and SUVmax collected at "final" evaluation (area under the curve (95% Confidence Interval): 0.80 (0.71–0.90) and 0.81 (0.72–0.90), respectively). Conclusion: The percentage variation in SUVmax in the time interval before and after completing neoadjuvant CRT, as well as DWI SI plus ADC and SUVmax obtained after completing neoadjuvant CRT, could be used to predict residual cervical cancer in LACC patients. From a cost point of view, the use of MRI and PET/CT is preferable. [ABSTRACT FROM AUTHOR]

Simple Summary: Inguinal node status represents one of the key elements in defining prognosis and treatment strategies in vulvar cancer patients. Preoperative lymph node staging is still a challenging topic. Several imaging methods are currently recommended in the guidelines (CT, PET/CT, MRI, US) based on performance data that are still not conclusive in the literature. Recently, ultrasound is emerging as the method of choice for preoperative evaluation of the inguinofemoral LN, but only when performed by experienced operators, given the limited reliability of subjective evaluation by unskilled operators. The morphonode predictive model represents an artificial intelligence tool that aims to overcome this limitation by supporting the standard ultrasound in adequately predicting the presence of lymph node metastases for improving preoperative surgical planning. We plan to proceed with further multicenter prospective validation and further develop the actual model, including both clinical and biological data. Ultrasound examination is an accurate method in the preoperative evaluation of the inguinofemoral lymph nodes when performed by experienced operators. The purpose of the study was to build a robust, multi-modular model based on machine learning to discriminate between metastatic and non-metastatic inguinal lymph nodes in patients with vulvar cancer. One hundred and twenty-seven women were selected at our center from March 2017 to April 2020, and 237 inguinal regions were analyzed (75 were metastatic and 162 were non-metastatic at histology). Ultrasound was performed before surgery by experienced examiners. Ultrasound features were defined according to previous studies and collected prospectively. Fourteen informative features were used to train and test the machine to obtain a diagnostic model (Morphonode Predictive Model). The following data classifiers were integrated: (I) random forest classifiers (RCF), (II) regression binomial model (RBM), (III) decisional tree (DT), and (IV) similarity profiling (SP). RFC predicted metastatic/non-metastatic lymph nodes with an accuracy of 93.3% and a negative predictive value of 97.1%. DT identified four specific signatures correlated with the risk of metastases and the point risk of each signature was 100%, 81%, 16% and 4%, respectively. The Morphonode Predictive Model could be easily integrated into the clinical routine for preoperative stratification of vulvar cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Currently, around 30% of vulvar cancer cases at first diagnosis are spread to the inguinal lymph nodes. Preoperative staging of patients affected by vulvar carcinoma is still a hot topic. To date, MRI has shown a great diagnostic accuracy on defining disease extension to soft tissue and deep organs. At present, regarding the study of inguinal nodes, the PET/CT scan has shown a high negative predictive value, although in the presence of a suspicious/positive report it should be taken with caution. We report the results of a study aimed to investigate the role of groin ultrasound in the assessment of lymph nodal status in vulvar cancer. Furthermore, this review represents the most accurate collection of papers available in the literature. This work demonstrates that groin ultrasound can be considered a valuable tool for risk assessment of the presence of groin lymph node metastases. Achieving a high diagnostic accuracy would allow tailored surgical planning with access to minimally invasive surgery techniques for an increasing number of patients. Objective. To determine the efficacy of ultrasound in assessing the inguinal lymph nodes in patients with vulvar cancer. Methods. A systematic review of published research up to October 2020 that compares the results of ultrasound to determine groin node status with histology was conducted. All study types that reported primary data on the role of ultrasound in the evaluation of groin lymph nodes in vulvar cancer were included in the systematic review. Data retrieved from the included studies were pooled in random-effects meta-analyses. Results. After the screening and selection process, eight articles were deemed pertinent for inclusion in the systematic review and meta-analysis. The random-effects model showed a pooled Se of 0.85 (95% CI: 0.81–0.89), Sp of 0.86 (95% CI: 0.81–0.91), PPV of 0.65 (95% CI: 0.54–0.79) and NPV of 0.92 (95% CI: 0.91–0.94). There was a pooled LR+ and LR− of 6.44 (95% CI: 3.72–11.4) and 0.20 (95% CI: 0.14–0.27), respectively. The pooled accuracy was 0.85 (95% CI: 0.80–0.91). Conclusions. Although the studies had small sample sizes, this review represents the best summary of the data so far. Ultrasound has revealed high sensitivity and high negative predictive value in the assessment of nodal status in vulvar cancer. [ABSTRACT FROM AUTHOR]

How do clinical rectovaginal examination and transvaginal ultrasound examination perform in the diagnosis of parametrial infiltration in patients with endometriosis? This was a multicentre prospective observational study. Patients with suspected deep endometriosis at clinical examination and/or at ultrasound evaluation and scheduled for surgery were included. Following multicentre multidisciplinary meetings, consensus was obtained on terms and methodology to define the parametrium at pelvic anatomy, ultrasound and surgery. Sensitivity, specificity, accuracy, and positive and negative likelihood ratios were calculated for clinical and ultrasound examinations with respect to surgery. In total, 195 women were selected for the present study and 164 were included in the analysis. Ultrasound examination had good to high specificity (>80%) for all parameters, except the left lateral parametrium (78.8%). The sensitivity of ultrasound examination was good to high for fixity of the right and left ovaries, uterosacral ligaments, retrocervix and rectovaginal space; and low for the anterior and lateral parametria, vagina, bladder and bowel. Clinical examination had good to high specificity for fixity of the left ovary, anterior parametrium, right uterosacral ligament, retrocervix and vagina; and low specificity for fixity of the right ovary, lateral parametrium, left uterosacral ligament and rectovaginal space. The sensitivity of clinical examination was good for the uterosacral ligaments and rectovaginal space, and low for the remaining parameters. Ultrasound examination provided good specificity for all the parameters, but sensitivity was low for the anterior and lateral parametria. Clinical examination provided good specificity for the anterior and posterior parametria, but sensitivity was low for the anterior and lateral parametria. Further prospective studies are needed to validate this methodology and confirm the results. [ABSTRACT FROM AUTHOR]

The current review sums up the literature on the diagnostic performance of models to predict malignancy in adnexal masses and the ability of ultrasound to make a specific diagnosis in adnexal masses. A summary of the role of ultrasound in assessing the extension of malignant ovarian disease is also provided. [ABSTRACT FROM AUTHOR]

Aims and Objectives/Purpose/Research Questions: The Alorese in eastern Indonesia are an Austronesian community who have inhabited two Papuan-speaking islands for approximately 600 years. Their language presents a paradox: contact with the neighbouring Papuan languages has led to both complexification and simplification. This article argues that these opposite outcomes of contact result from two distinct scenarios, and formulates a hypothesis about a shift in multilingual patterns in Alorese history. Design/Methodology/Approach: To formulate a hypothesis about the discontinuity of multilingual patterns, this article first sketches the past and present multilingual patterns of the Alorese by modelling language contact outcomes in terms of bilingual optimisation strategies. This is followed by a comparison of the two scenarios to pinpoint similarities and differences. Data and Analysis: Previous research shows that two types of contact phenomena are attested in Alorese: (a) complexification arising from grammatical borrowings from Papuan languages, and (b) morphological simplification. The first change is associated with prolonged child bilingualism and is the result of Papuan-oriented bilingual strategies, while the latter change is associated with adult second language (L2) learning and is the result of universal communicative strategies. Findings/Conclusions: Complexification and simplification are the results of two different layers of contact. Alorese was first used in small-scale bilingual communities, with widespread symmetric multilingualism. Later, multilingualism became more asymmetric, and the language started to undergo a simplification process due to the considerable number of L2 speakers. Originality: This article is innovative in providing a clear case study showing discontinuity of multilingual patterns, supported by linguistic and non-linguistic evidence. Significance/Implications: This article provides a plausible explanation for the apparent paradox found in Alorese, by showing that different outcomes of contact in the same language are due to different patterns of acquisition and socialisation. This discontinuity should be taken into account by models of language contact. [ABSTRACT FROM AUTHOR]

Aims and Objectives/Purpose/Research Questions: This article examines the role of social-psychological factors in the development of heritage Ambon Malay in the Netherlands. More specifically, it aims to answer this question: Can social-psychological factors account for the different frequency of Dutch-like structures among heritage speakers? Design/Methodology/Approach: Data from 32 Ambon Malay heritage speakers and 27 Ambon Malay homeland speakers were collected by means of video stimuli and a sociolinguistic interview. Data and Analysis: The database provides six linguistic variables and three social-psychological factors. The linguistic variables are as follows: the pre-verbal marker ada; the definite marker =nya; the double object construction; the prepositional phrase and adjectival phrase in resultative constructions; the pre-nominal order for the demonstrative itu and the numeral satu ‘one’. The social-psychological factors are where the speaker lives, onset of Dutch bilingualism and attitude. The effect of the social-psychological factors on the linguistic variables was assessed using a multivariate general linear model. Findings/Conclusions: The results show that place where the speaker lives is the best predictor. Heritage speakers living outside a Moluccan ward have a higher rate of Dutch-like features than speakers living inside a Moluccan ward. In some cases, sequential bilinguals are more innovative than simultaneous bilinguals. Finally, speakers with only a mild positive attitude towards the heritage language have a higher rate of Dutch-like features. Originality: Unlike previous studies, this article does not test the role of social-psychological factors against self-ratings of heritage language proficiency, but it uses real language data. Significance/Implications: The theoretical significance of this study is to bridge the gap between the sphere of language structure and the sphere of language use and language attitude. An additional value lies in its findings that frequent use of the heritage language means not only a higher rate of maintenance but also accelerated change. [ABSTRACT FROM AUTHOR]

This article discusses the plural word hire in Alorese, an Austronesian language spoken on the islands of Alor and Pantar, in eastern Indonesia. Following the methodological requisites for contact-induced change, I claim that the plural word hire emerged through contact with Papuan Alor-Pantar languages, because (i) Alorese was and still is spoken in close contact with Alor-Pantar languages; (ii) Alorese and the neighboring Alor-Pantar languages share the presence of a plural word, and their plural words have similar syntactic and semantic properties; (iii) Alor-Pantar languages had plural words before they came into contact with Alorese; and (iv) Alorese did not have the plural word hire before it came into contact with Alor-Pantar languages. The innovation of hire is a case of contact-induced grammaticalization, whereby the form is inherited and developed from an original third person plural pronoun going back to Proto-Malayo-Polynesian *si-ida, while the function of the plural word is borrowed from the neighboring Alor-Pantar languages. [ABSTRACT FROM AUTHOR]

Aims and Objectives/Purpose/Research Questions: This paper investigates the effects of Dutch on the tense-aspect system of heritage Ambon Malay, a variety spoken by Dutch-Ambon Malay bilinguals in the Netherlands. The study asks whether the cross-linguistic contrasts between the two languages – Dutch obligatorily marks past/non-past and finiteness, whereas Ambon Malay lacks a grammaticalized expression of these distinctions – has an effect on the aspectual system of heritage Ambon Malay. Design/Methodology/Approach: The database for the study consists of video descriptions provided by 32 bilingual speakers (the experimental groups) and by three control groups: 27 homeland speakers of Ambon Malay, 5 first generation speakers of Ambon Malay in the Netherlands (late bilinguals), and 10 monolingual speakers of Dutch. Data and Analysis: The frequency and distribution of aspect markers is analysed statistically in the four groups. Findings/Conclusions: The analysis of the data reveals that, under the influence of Dutch, the Ambon Malay progressive marker ada has undergone a shift in temporal status and frequency and it is now interpreted as a marker of present tense, as well as of progressive aspect. The other two aspect markers, the iamitive/perfective su and verbal reduplication (iterative) are used significantly less by heritage speakers. Originality: This study shows that when a grammatical category is present and productive in the dominant language of a bilingual heritage speaker, but not in the heritage language, there is a great likelihood that it will undergo contact-induced grammaticalization, even in a relatively short time contact situation. The study also shows that input-related factors, such as transparency and phonological salience, contribute to the (in)stability of aspectual forms in the heritage language. Significance/Implications: This finding has implication for the incomplete acquisition perspective on heritage languages, which sees these languages as grammatically simplified systems (see, e.g., Montrul, 2009; Polinsky, 2008), because it shows that heritage languages can also gain grammatical distinctions previously absent in the (homeland) language. [ABSTRACT FROM AUTHOR]

Highlights • We studied a patient with autophagic vacuolar myopathy. • We detected a reported variant in CLN3. • CLN3 should be considered in autophagic vacuolar myopathy. Abstract We present a 29-year-old man with visual failure since childhood, muscle weakness, subtle heart muscle hypertrophy, and seizures who was initially considered to be affected by a mitochondrial encephalomyopathy because of the multiple unspecific involvement of brain, muscle and retinal tissues. Only the muscle biopsy findings correctly guided the genetic investigations and the identification of an autophagic vacuolar myopathy due to a homozygous mutation in CLN3. We believe that information in autophagic muscle disorders should further alert clinicians to consider CLN3 in individuals with vacuolar myopathy, especially if they have visual and cardiac involvement. [ABSTRACT FROM AUTHOR]

Objective: To evaluate anti-Müllerian hormone (AMH) concentrations and antral follicle counts (AFCs) in the prediction of pregnancy outcomes after controlled ovarian stimulation among women undergoing intrauterine insemination.Methods: A retrospective study included women with unexplained infertility aged 41years or younger who attended a fertility clinic in Italy between December 2009 and May 2014. Ovarian stimulation was achieved with recombinant follicle-stimulating hormone or highly purified human menopausal gonadotropin. Receiver operating characteristic curves were generated to predict ongoing pregnancy. The primary outcome was the association between AMH/AFC and ongoing pregnancy, and was assessed by logistic regression.Results: Overall, 276 women were included, of whom 43 (15.6%) achieved ongoing pregnancy. Multivariate analysis showed that women with a serum day-3 concentration of AMH higher than 2.3ng/mL were more likely to have ongoing pregnancy than were those with a concentration lower than 2.3ng/mL (odds ratio 5.84, 95% confidence interval 2.38-14.31; P<0.001). No associations were recorded for AFCs.Conclusion: AMH should be used to predict the pregnancy outcome of intrauterine insemination. [ABSTRACT FROM AUTHOR]

Objective Women affected by PCOS and psoriasis are more likely to have insulin-resistance, hyperinsulinemia, reduced HDL cholesterol levels and a more severe degree of skin disease than those with psoriasis alone. The mechanism underlying this association between PCOS and psoriasis is currently unknown. The aim of the present study was to evaluate the features of psoriasis and the psoriasis severity scores in the different PCOS phenotypes and in age and body mass index (BMI)-matched psoriatic control patients. Study design A cross-sectional study was performed on 150 psoriatic patients: 94 PCOS and 56 age- and BMI-matched controls. PCOS patients were diagnosed and divided into four phenotypes according to Rotterdam criteria: A – patients with complete phenotype with hyperandrogenism (H) plus oligoamenorrhea (O) plus polycystic ovary (PCO) on ultrasound examination; B – patients with H plus O (without PCO); C – patients with H plus PCO (ovulatory phenotype); D – patients with O plus PCO (without H). The patient's Psoriasis Area and Severity Index (PASI) as well as the Physician's Global Assessment (PGA) were calculated. A PASI score ≥10 was correlated with common indicator of severe disease. A PGA ≥4 was considered as a condition of moderate to severe disease. Results Among the four phenotypes investigated, the group with complete phenotype (H plus O plus PCO) had a higher prevalence of patients with patient's PASI ≥10 compared to controls (Odds Ratio (OR) 4.71, 95% confidence intervals (CI) 1.59–13.95). The group with O plus PCO had a higher prevalence of patients with PGA ≥4 compared to controls (OR 26.79, 95% CI 3.40–211.02) while the ovulatory group had a lower prevalence of patients with PGA ≥4 (OR 0.06, 95% CI 0.01–0.51). Conclusions The ovulatory phenotype displays a milder psoriasis form than other phenotypes while the phenotypes with oligoamenorrhea presented higher severity scores of disease than other phenotypes and control group. [ABSTRACT FROM AUTHOR]

Objective Tubal patency in women with endometriosis has traditionally been evaluated by laparoscopy. The aim of this study was to investigate the accuracy of hysterosalpingo-contrast-sonography (HyCoSy) in the assessment of tubal patency in these women. Study design A retrospective study was conducted at Physiopathology of Human Reproduction Unit. Infertile women who underwent HyCoSy and then a laparoscopy (dye test) within 6 months from the HyCoSy were included. Tubal patency was assessed by HyCoSy and the findings were compared with the results of laparoscopy, which was considered the gold standard for assessment of tubal patency. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) and positive and negative likelihood ratios (Lh+, Lh−) were calculated including the 95% confidence interval (CI). Results A total of 1452 women underwent HyCoSy and 126 of them received a laparoscopy within 6 months from the HyCoSy. Of the 126 women, 42 (33.3%) had a diagnosis of pelvic endometriosis and 84 (66.7%) had no endometriosis. In the endometriosis population, HyCoSy showed a sensitivity, specificity, PPV, NPV, Lh+ and Lh− of 85% (95% CI 62–96), 93% (95% CI 82–97), 81% (95% CI 58–94), 94% (95% CI 84–98), 12.6 (95% CI 4.8–33) and 0.15 (95% CI 0.05–0.4) respectively. In the non-endometriosis group, HyCoSy showed a sensitivity, specificity, PPV, NPV, LR+ and LR− of 85% (95% CI 65–95), 93% (95% CI 87–96), 71% (95% CI 53–85), 97% (95% CI 92–99), 13.2 (95% CI 6.9–25) and 0.15 (95% CI 0.06–0.3) respectively. The diagnostic accuracy of HyCoSy was 91% in the endometriosis group and 92% in the non-endometriosis patients. Conclusions HyCoSy showed high accuracy in evaluating tubal patency in infertile non-endometriosis women and in those affected by endometriosis. [ABSTRACT FROM AUTHOR]

STUDY QUESTION: Is the treatment with recombinant FSH (rFSH) plus recombinant LH (rLH) more effective than highly purified (HP)-hMG in terms of ongoing pregnancy rate (PR) in women ≥35 years of age undergoing intrauterine insemination (IUI) cycles? SUMMARY ANSWER: The ongoing PR was not significantly different in women treated with rFSH plus rLH or with HP-hMG. WHAT IS KNOWN ALREADY: Although previous studies have shown beneficial effects of the addition of LH activity to FSH, in terms of PR in patients aged over 34 years having ovulation induction, no studies have compared two different gonadotrophin preparations containing LH activity inwomen ≥35 years of age in IUI cycles. STUDY DESIGN, SIZE, DURATION: A single-centre RCT was performed between May 2012 and September 2013 with 579 women ≥35 years of age undergoing IUI cycles. The patients were randomly assigned to one of the two groups, rFSH in combination with rLH group or HP-hMG (Meropur) group, by giving them a code number from a computer generated randomization list, in order of enrolment. The randomization visit took place on the first day of ovarian stimulation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Five hundred and seventy-nine patients with unexplained infertility or mild male factor undergoing IUI cycles were recruited in a university hospital setting. All women were enrolled in this study only for one cycle of treatment. Five hundred and seventy-nine cycles were included in the final analysis. Two hundred and ninety patients were treated with rFSH in combination with rLH and 289 patients were treated with HP-hMG. The ovarian stimulation cycle started on the third day of the menstrual cycle and the starting gonadotrophin doses used were 150 IU/day of rFSH plus 150 IU/day of rLH or 150 IU/day of HP-hMG. The drug dose was adjusted according to the individual follicular response. A single IUI per cycle was performed 34-36 h after hCG injection. MAIN RESULTS AND THE ROLE OF CHANCE: The main outcome measures were ongoing PR and number of interrupted cycles for high risk of ovarian hyperstimulation syndrome (OHSS). Ongoing pregnancy rates were 48/290 (17.3%) in the recombinant group versus 35/289 (12.2%) in the HP-hMG group [(odds ratio (OR) 1.50, 95% CI 0.94-2.41, P = 0.09]. The number of interrupted cycles for high risk of OHSS was 13/290 (4.5%) in the rFSH plus rLH group and 2/289 (0.7%) in the HP-hMG group (OR 6.73, 95% CI 1.51-30.12, P = 0.013). LIMITATIONS, REASONS FOR CAUTION: One of the limitations of this study was the early closure and the ongoing PR could be overestimated. Both patient and gynaecologist were informed of the assigned treatment. WIDER IMPLICATIONS OF THE FINDINGS: Our results demonstrated the lack of differences in terms of ongoing PR between recombinant product and HP-hMG, in women ≥35 years undergoing controlled ovarian stimulation for IUI cycles. HP-hMG was safer than recombinant gonadotrophin concerning the risk of OHSS. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: NCT01604044. [ABSTRACT FROM AUTHOR]

The primary aim of the present study was to investigate the prognostic impact (defined as disease-free—DFS and overall survival—OS) of the ultrasound scan tumor parameters, patients' anthropometric parameters, and their combination in early-stage cervical cancer. The secondary aim was to assess the relation between ultrasound characteristics and pathological parametrial infiltration. This is a retrospective, single-center, observational cohort study. Consecutive patients with clinical FIGO 2018 stage IA1–IB2 and IIA1 cervical cancer who underwent preoperative ultrasound examination and radical surgery between 02/2012 and 06/2019 were included. Patients who underwent neo-adjuvant treatment, fertility sparing surgery, and pre-operative conization were excluded. Data from 164 patients were analyzed. Body mass index (BMI) ≤20 Kg/m2 (p < 0.001) and ultrasound tumor volume (p = 0.038) were related to a higher risk of recurrence. The ratios between ultrasound tumor volume and BMI, ultrasound tumor volume and height, and ultrasound largest tumor diameter and BMI were significantly related to a higher risk of recurrence (p = 0.011, p = 0.031, and p = 0.017, respectively). The only anthropometric characteristic related to a higher risk of death was BMI ≤20 Kg/m2 (p = 0.021). In the multivariate analysis, the ratio between ultrasound-measured largest tumor diameter and cervix-fundus uterine diameter (with 37 as the cut-off) was significantly associated with pathological microscopic parametrial infiltration (p = 0.018). In conclusion, a low BMI was the most significant anthropometric biomarker impairing DFS and OS in patients with apparent early-stage cervical cancer. The ratios between ultrasound tumor volume and BMI, ultrasound tumor volume and height, and ultrasound largest tumor diameter and BMI significantly affected DFS but not OS. The ratio between ultrasound-measured largest tumor diameter and cervix-fundus uterine diameter was related to parametrial infiltration. These novel prognostic parameters may be useful in pre-operative workup for a patient-tailored treatment in early-stage cervical cancer. [ABSTRACT FROM AUTHOR]

Domains where languages have two or more competing syntactic constructions expressing the same meaning may be problematic for bilingual heritage speakers. One such variable domain is the resultative constructions in heritage Ambon Malay, a variety spoken in the Netherlands by Dutch-Ambon Malay bilinguals. In Ambon Malay, resultatives are expressed mostly by means of verb serialization (SVC), although resultative prepositional phrases (PP) and adjectival phrases (AP) also occur. In Dutch, resultative constructions usually involve verb particles, PPs and APs. This overlap of structures poses the conditions for transfer effects between the two languages. The frequency distribution of SVCs, PPs and APs is investigated in semi-spontaneous speech from heritage speakers of Ambon Malay and compared to that of baseline speakers. Heritage speakers show an increase in the frequency of constructions shared by both languages (PPs and APs), while they underuse the constructions attested only in the heritage language (SVC). [ABSTRACT FROM AUTHOR]

Objective: Toevaluatethelong-termeffectsofdrospirenone(DRSP)/ethinylestradiol(EE)alone,metforminalone,andDRSP/ + null EE-metforminonCD4 CD28 Tlymphocytesfrequency,acardiovascularriskmarker,inpatientswithhyperinsulinemic polycysticovarysyndrome(PCOS). Design: Randomizedclinicaltrial. Interventions: Ninetythreepatientswithhyper- insulinemicPCOSwereagematchedandbodymassindexmatchedandrandomizedtoreceivea6monthsdailytreatmentwith DRSP(3mg)/EE(0.03mg),ormetformin(1500mg),orDRSP/EEcombinedwithmetformin. MainOutcomeMeasures: + null CD4 CD28 T-cellfrequencies. Results: TheDRSP/EEandmetformingroupsdidnotshowanysignificantchangeinthe + null + null CD4 CD28 frequencycomparedtothebaseline.Interestingly,astatisticallysignificantdecreaseinCD4 CD28 frequency occurredafter6monthsofDRSP/EE-metformin(median 3-1.5; P <.01).Ofnote,thisstatisticallysignificantassociationwas confirmedafteradjustingforbaselinevaluesinDRSP/EE-metformingroupbyanalysisofcovariance(P <.05). Conclusions: In womenwithhyperinsulinemicPCOS,combinedtherapywithDRSP/EEandmetforminmayreducecardiovascularrisk. [ABSTRACT FROM AUTHOR]

Abstract: Mutations in the fukutin gene were first identified in Japanese patients with classic Fukuyama congenital muscular dystrophy, a severe form of congenital muscular dystrophy associated with cobblestone lissencephaly and ocular defects. Patients of different ethnicities and with milder phenotypes, including limb girdle muscular dystrophy and cardiomyopathy without brain impairment, have also been reported. The hallmark of this disorder, regardless of the clinical outcome, is moderate-to-severe hypoglycosylation of alpha-dystroglycan in muscle sections. We describe the case of a boy harboring two novel mutations in fukutin gene and presenting a five-year history of asymptomatic hyperCKemia, without overt muscle, brain or ocular involvement. Genetic investigations, guided by the presence of moderate myopathic changes on muscle biopsy with loss of immunodetectable alpha-dystroglycan, led to a definitive diagnosis. Cardiac and echocardiographic examinations at follow-up disclosed low normal left ventricular function but no active cardiovascular symptoms. We suggest that fukutin mutations should be sought in asymptomatic hyperCKemia and subclinical heart dysfunction. [Copyright &y& Elsevier]

Objective: To study the frequency of CD4+CD28null T cells, which are aggressive T lymphocytes associated with recurrent coronary instability and type 2 diabetes mellitus, in different polycystic ovary syndrome (PCOS) phenotypes and in age- and body mass index–matched healthy women. Design: Retrospective cohort observational study. Setting: Unit of human reproductive pathophysiology, university hospital. Patient(s): A total of 167 PCOS patients and 102 control subjects. Intervention(s): None. Main Outcome Measure(s): CD4+CD28null T cell frequency, high-sensitive C-reactive protein levels, and other glucose-metabolic parameters. Result(s): CD4+CD28null frequency was significantly higher in all PCOS groups than in control subjects. CD4+CD28null frequency was significantly higher in nonhyperandrogenic phenotype (5.7%, range 3.2–7.1) than in phenotypes with hyperandrogenism (H) + oligoamenorrhea (O) + polycystic ovary (PCO) (3.5%, range 1–5.8), H + O (3%, range 1.8–4.7), and H + PCO (2.63%, range 1.2–4.1). The relative risk of non-H phenotype for PCOS women in the highest quartile for CD4+CD28null frequency compared with PCOS women with the lowest quartile was 3.2 (95% confidence interval 1.9–5.8). Conclusion(s): Cardiovascular risk evaluation should be performed in all PCOS phenotypes. In particular, we demonstrated that the non-H phenotype has potentially increased cardiovascular risk in terms of CD4+CD28null frequency. [ABSTRACT FROM AUTHOR]

Autism is a complex behavioral disorder that develops prior to age three years and is distinguished by high heritability. Many genes predisposing to autism spectrum disorders (ASDs) have been identified. These findings have demonstrated that ASDs are etiologically heterogeneous; although, the mutations underlying ASDs are identifiable only in a minority of patients. Indeed, the causes of ASDs are unknown in more than 70% of patients. Recently, we have described two unrelated families whose affected individuals display a characteristic triad of symptoms of autism; such as impairments in social interaction, impairments in communication, restricted interests and repetitive behavior. They also displayed other symptoms commonly observed in autistic individuals; such as gait imbalance, clumsiness, mental retardation and epilepsy. The genetic analysis of these families resulted in the identification of new heterozygous point mutations in the KCNJ10 gene that encodes the inwardly-rectifying K+ channel Kir4.1 expressed predominantly, but not exclusively, in astrocytes. Functionally, the mutated channels exhibited a phenotype consistent with gain-offunction defects. These new findings highlight the emerging role of inwardly-rectifying K+ channels and astrocyte dysfunction in autism spectrum disorders associated with epilepsy. [ABSTRACT FROM AUTHOR]

Objective: To demonstrate the noninferiority of highly purified menotropin (HP-hMG) compared with recombinant FSH (rFSH) regarding clinical pregnancy rate (PR) in intrauterine insemination (IUI) cycles. Design: Prospective randomized noninferiority trial. Setting: Unit of physiopathology of human reproduction, university hospital. Patient(s): Five hundred twenty-three patients with unexplained infertility or mild male infertility undergoing controlled ovarian hyperstimulation for IUI. Intervention(s): Patients were randomized for treatment with rFSH (262 patients) or HP-hMG (261 patients). Insemination was performed 34–36 hours after hCG injection. Main Outcome Measure(s): The primary outcome was clinical pregnancy rate (PR). The secondary outcome was the number of interrupted cycles for high risk of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. Result(s): The clinical PR was 19.7% (95% confidence interval [CI] 15.3%–25.1%) in the HP-hMG group and 21.4% (95% CI 16.9%–26.8%) in the rFSH group [absolute difference −1.7% (95% CI −8.6%–5.2%)]; therefore, the noninferiority was demonstrated. The number of interrupted cycles for OHSS risk and multiple pregnancy was significanty higher in the rFSH group, 8.4% (95% CI 5.6%–12.4%) than in the HP-hMG group 1.2% (95% CI 0.4%–3.3%) [absolute difference −7.27% (95% CI −11.3 to −3.7)]. Conclusion(s): HP-hMG is not inferior compared with rFSH regarding clinical PR. [ABSTRACT FROM AUTHOR]

Purpose: Stress urinary incontinence (SUI) is usually treated with mid-urethral slings. The best approach is still debated and the relationship between slings and pelvic structures is not completely understood. The aim of this study is to identify any difference between trans-obturator tape (TOT) and single incision sling (minisling). Methods: Patients submitted to TOT or minisling were included in the study. Q-tip and stress test, ICIQ-SF questionnaire, PGI-I validated score, and 2D/3D transvaginal ultrasound parameters were collected at 1- and 6-month follow-up. Correlations between ultrasound parameters and clinical outcomes, PGI-I and ICIq-SF, were performed. Results: 61 patients were included in the study. PGI-I score was significantly lower in the minisling group than in TOT group at 1-month (p = 0.016) and 6-month follow-up (p = 0.076). The median distance between the sling and the lumen of urethra was significantly higher and the angle between the branches of the sling was significantly narrower in the minisling group. There were significant differences in distances between the sling and the bladder neck at 1-month and 6-month follow-up. An inverse correlation between angle of the branches and the Q-tip test was observed (p = 0.059 Pearson's Rho − 0.578). PGI-I correlated also with angle of the branches (p = 0.009, Pearson's Rho 0.503). Conclusion: Patients undergoing TOT or minisling are similarly satisfied but show differences at ultrasound exam at 1- and 6-month follow-up. Pelvic floor ultrasound could be used in a short-term follow-up to visualize the sling position and to plan the most appropriate follow-up strategy. [ABSTRACT FROM AUTHOR]

This article describes and compares give -constructions in three languages of eastern Indonesia, Lamaholot (Austronesian), Alorese (Austronesian), and Adang (Papuan), with the aim of detecting structural convergence in Alorese. Lamaholot and Alorese are closely related, while Alorese has undergone contact-induced change due to contact with Papuan languages spoken in close proximity, such as Adang. To investigate structural convergence, we systematically compare the types and frequencies of give -constructions in these three languages. The data were obtained by using a common set of eight visual stimuli. The results show that Alorese and Adang share a preference for encoding 'give' events in serial verb constructions, while Lamaholot uses prepositional object constructions or multiverb constructions. We conclude that, in the domain of give -constructions, there is a higher degree of structural isomorphism between Alorese and Adang than there is between Alorese and its sister language Lamaholot. Such structural isomorphism is the outcome of contact-induced convergence; more specifically, we propose that convergence took place by a process of grammatical calquing carried out by children and preadolescents who were bilingual in Alorese and one or more Papuan languages. [ABSTRACT FROM AUTHOR]

Background: Several diagnostic prediction models to help clinicians discriminate between benign and malignant adnexal masses are available. This study is a head-to-head comparison of the performance of the Assessment of Different NEoplasias in the adneXa (ADNEX) model with that of the Risk of Ovarian Malignancy Algorithm (ROMA). Methods: This is a retrospective study based on prospectively included consecutive women with an adnexal tumour scheduled for surgery at five oncology centres and one non-oncology centre in four countries between 2015 and 2019. The reference standard was histology. Model performance for ADNEX and ROMA was evaluated regarding discrimination, calibration, and clinical utility. Results: The primary analysis included 894 patients, of whom 434 (49%) had a malignant tumour. The area under the receiver operating characteristic curve (AUC) was 0.92 (95% CI 0.88–0.95) for ADNEX with CA125, 0.90 (0.84–0.94) for ADNEX without CA125, and 0.85 (0.80–0.89) for ROMA. ROMA, and to a lesser extent ADNEX, underestimated the risk of malignancy. Clinical utility was highest for ADNEX. ROMA had no clinical utility at decision thresholds <27%. Conclusions: ADNEX had better ability to discriminate between benign and malignant adnexal tumours and higher clinical utility than ROMA. Clinical trial registration: clinicaltrials.gov NCT01698632 and NCT02847832. [ABSTRACT FROM AUTHOR]

Introduction: Mutations in the neurofilament polypeptide light chain (NEFL) gene account for <1% of all forms of Charcot-Marie-Tooth (CMT) diseases and present with different phenotypes, including demyelinating, axonal and intermediate neuropathies, and with diverse pattern of transmission, with dominant and recessive inheritance being described. Methods: Here, we present clinical and molecular data in two new unrelated Italian families, affected with CMT. Results: We studied fifteen subjects (11 women, 4 men), age range 23–62 year. Onset of symptoms was mainly in childhood, with running/walking difficulties; some patients were pauci-asymptomatic; almost all shared variably distributed features of absent/reduced deep tendon reflexes, impaired gait, reduced sensation, and distal weakness in the legs. Skeletal deformities were seldom documented and were of mild degree. Additional features included sensorineural hearing loss in 3 patients, underactive bladder in 2 patients, and cardiac conduction abnormalities, requiring pacemaker implantation, in one child. Central nervous system (CNS) impairment was not documented in any subject. Neurophysiological investigation disclosed feature suggestive of demyelinating sensory-motor polyneuropathy in one family and resembling an intermediate form in the other. Multigene panel analysis of all known CMT genes revealed two heterozygous variants in NEFL: p.E488K and p.P440L. While the latter change segregated with the phenotype, the p.E488K variant appeared to act as a modifier factor being associated with axonal nerve damage. Conclusions: CMT related to P440L mutation in NEFL is associated with a mild, childhood-onset phenotype, showing prevalently sensory distal limbs involving and with motor impairment predominantly involving anterolateral leg muscles, in the absence of CNS involvement. Additional findings, never reported so far in patients with NEFL mutation, are cardiological and urinary dysfunctions. Our study expands the array of clinical features associated with NEFL-related CMT. [ABSTRACT FROM AUTHOR]

Background: Ovarian endometriomas are classified as benign ovarian lesions. During pregnancy endometriomas may undergo major morphological changes which are referred to as 'decidualisation'. Decidualised ovarian endometrioma may resemble malignant ovarian tumours on ultrasound examination. The aim was to study variations in the morphology and size of ovarian endometriomas diagnosed on ultrasound during pregnancy.Methods: We searched our database to identify pregnant women who were diagnosed with ovarian endometriomas on ultrasound in order to study the effect of pregnancy on their morphological characteristics. In women who underwent serial scans during pregnancy we examined the changes in the size of endometriomas with advancing gestation.Results: Twenty four patients with a total of 34 endometriomas were included in the analysis. All women were managed expectantly during pregnancy. On the first ultrasound scan 29/34 (85.3%, 95% CI 73.4 - 97.2) endometriomas appeared unilocular with fine internal echoes ('ground glass' contents) and they were poorly vascularised on Doppler examination. 1/34 (2.9% 95% CI 0.0 - 8.5) endometrioma was multilocular, with regular margins, 'ground glass' contents and it was also poorly vascularised. 4/34 (11.8%, 95% CI 1.0 - 22.6) had sonographic features suggestive of decidualisation such as thick and irregular inner wall, papillary projections and highly vascular on Doppler examination. The endometriomas showed a tendency to decrease in size during pregnancy.Conclusions: Pregnancy has a major effect on the size and morphological appearances of ovarian endometriomas. Rapid regression of decidualised endometriomas is a helpful feature which could be used to confirm their benign nature. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate magnetic resonance (MR) imaging-based radiomics models for high-risk endometrial cancer (EC) prediction preoperatively, to be able to estimate deep myometrial invasion (DMI) and lymphovascular space invasion (LVSI), and to discriminate between low-risk and other categories of risk as proposed by ESGO/ESTRO/ESP (European Society of Gynaecological Oncology—European Society for Radiotherapy & Oncology and European Society of Pathology) guidelines. Methods: This retrospective study included 96 women with EC who underwent 1.5-T MR imaging before surgical staging between April 2009 and May 2019 in two referral centers divided into training (T = 73) and validation cohorts (V = 23). Radiomics features were extracted using the MODDICOM library with manual delineation of whole-tumor volume on MR images (axial T2-weighted). Diagnostic performances of radiomic models were evaluated by area under the receiver operating characteristic (ROC) curve in training (AUCT) and validation (AUCV) cohorts by using a subset of the most relevant texture features tested individually in univariate analysis using Wilcoxon–Mann–Whitney. Results: A total of 228 radiomics features were extracted and ultimately limited to 38 for DMI, 29 for LVSI, and 15 for risk-classes prediction for logistic radiomic modeling. Whole-tumor radiomic models yielded an AUCT/AUCV of 0.85/0.68 in DMI estimation, 0.92/0.81 in LVSI prediction, and 0.84/0.76 for differentiating low-risk vs other risk classes (intermediate/high-intermediate/high). Conclusion: MRI-based radiomics has great potential in developing advanced prognostication in EC. [ABSTRACT FROM AUTHOR]

Brief periods (a few seconds) of cyclic coronary occlusions applied early in reperfusion induce a cardioprotection against infarct size, called postconditioning (PostC) in which B2-bradykinin receptors play a pivotal role. Since angiotensin-converting enzyme (ACE) inhibitors reduce degradation of kinins, we studied the effects of PostC on infarct size and postischemic myocardial dysfunction in both normotensive (WKY) and spontaneously hypertensive rats (SHR) acutely or chronically treated with the ACE inhibitor Captopril. Isolated hearts from SHR and WKY rats were subjected to the following protocols: (a) ischemia for 30- and 120-min reperfusion (I/R); (b) I/R + PostC protocol (5-cycles 10-s I/R); (c) pretreatment with Captopril for 4-weeks before to subject the hearts to I/R with or without PostC maneuvers. Some SHR hearts were treated with Captopril during the 20- or 40-min early reperfusion with or without PostC maneuvers. Cardiac function was assessed in vivo with echocardiography. Left ventricular pressure and infarct size were measured ex vivo. Chronic Captopril significantly reduced left ventricular hypertrophy in SHR, and reduced infarct size in both WKY and SHR hearts. PostC maneuvers significantly reduced infarct size in WKY, but not in SHR hearts. Yet, PostC slightly improved postischemic systolic function in untreated SHR. Captopril given in reperfusion was unable to limit I/R injury in SHR hearts. Data show that PostC protection against infarct size is blunted in SHR and that PostC is unable to add its protective effect to those of chronic Captopril, which per se reduces cardiac hypertrophy and heart susceptibility to I/R insult. [ABSTRACT FROM AUTHOR]

Abstract: A method conceived for automatic recognition of mass loss of concrete using data acquired by terrestrial laser scanner is presented here. The method is based on computation of mean and Gaussian curvatures of the surface and on piecewise comparison of the corresponding distributions, since these distributions strongly change if an area is affected by damage. This contactless damage recognition system, which could be applied together with other NDT techniques to provide a complete picture of the health of the observed structure, has been successfully applied to a concrete bridge. [Copyright &y& Elsevier]

Purpose: We describe seven Italian families with generalized epilepsy with febrile seizures plus (GEFS+), in which mutations of SCN1A, SCN1B, and GABRG2 genes were excluded and compare their clinical spectrum with that of previously reported GEFS+ with known mutations. Methods: We performed a clinical study of seven families (167 individuals). The molecular study included analysis of polymerase chain reaction (PCR) fragments of SCN1A and SCN1B exons by denaturing high-performance liquid chromatography (DHPLC) and direct sequencing of GABRG2 in all families. We excluded SCN1A, SCN1B, and GABRG2 genes with linkage analysis in a large pedigree and directly sequenced SCN2A in a family with neonatal–infantile seizures onset. We compared the epilepsy phenotypes observed in our families with those of GEFS+ families harboring mutations of SCN1A, SCN1B, and GABRG2 and estimated the percentage of mutations of these genes among GEFS+ cases by reviewing all published studies. Results: Inheritance was autosomal dominant with 69% penetrance. Forty-one individuals had epilepsy: 29 had a phenotype consistent with GEFS+; seven had idiopathic generalized epilepsy (IGE); in three, the epilepsy type could not be classified; and two were considered phenocopies. Clinical phenotypes included FS+ (29.2%), FS (29.2%), IGE (18.2%), FS+ with focal seizures (13%) or absence seizures (2.6%), and FS with absence seizures (2.6%). Molecular study of SCN1A, SCN2A, SCN1B, and GABRG2 did not reveal any mutation. Results of our study and literature review indicate that mutations of SCN1A, SCN2A, SCN1B, and GABRG2 in patients with GEFS+ are rare. Conclusions: The most frequently observed phenotypes matched those reported in families with mutations of the SCN1A, SCN1B, and GABRG2 genes. IGE and GEFS+ may overlap in some families, suggesting a shared genetic mechanism. The observation that 13% of affected individuals had focal epilepsy confirms previously reported rates and should prompt a reformulation of the “GEFS+” concept to include focal epileptogenesis. [ABSTRACT FROM AUTHOR]

Background: Charcot-Marie-Tooth disease (CMT) type 4B3 (CMT4B3) is a rare form of genetic neuropathy associated with variants in the MTMR5/SBF1 gene. MTMR5/SBF1 is a pseudophosphatase predicted to regulate endo-lysosomal trafficking in tandem with other MTMRs. Although almost ubiquitously expressed, pathogenic variants primarily impact on the peripheral nervous system, corroborating the involvement of MTMR5/SBF1 and its molecular partners in Schwann cells-mediated myelinization. Case presentation: We report a case of severe CMT4B3 characterized by early-onset motor and axonal polyneuropathy in an Italian child in absence of any evidence of brain and spine MRI abnormalities or intellectual disability and with a biochemical profile suggestive of mitochondrial disease. Using an integrated approach combining both NGS gene panels and WES analysis, we identified two novel compound heterozygous missense variants in MTMR5/SBF1 gene, p.R763H (c.2291G > A) and p.G1064E (c.3194G > A). Studies in muscle identified partial defects of oxidative metabolism. Conclusion: We describe the first case of an early onset severe polyneuropathy with motor and axonal involvement, due to recessive variants in the MTMR5/SBF1 gene, with no evidence of brain and spine MRI abnormalities, intellectual disability, no clinical and neurophysiological evidences of distal sensory impairment, and rapid neuromuscular deterioration. This report suggests that MTMR5/SBF1 should be considered in cases of infantile-onset CMT with secondary mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Vortioxetine is a multimodal antidepressant that potently antagonizes 5-HT3 serotonin receptors, inhibits the high-affinity serotonin transporter, activates 5-HT1A and 5-HT1B receptors, and antagonizes 5-HT1D and 5-HT7 receptors. 5-HT3 receptors largely mediate the hyperalgesic activity of serotonin that occurs in response to nerve injury. Activation of 5-HT3 receptors contributes to explain why selective serotonin reuptake inhibitors, such as fluoxetine, are not indicated in the treatment of neuropathic pain. Here, we studied the analgesic action of vortioxetine in the chronic constriction injury model of neuropathic pain in mice. Vortioxetine was injected once a day for 27 days at doses (10 mg/kg, intraperitoneally) that determine >90% 5-HT3 receptor occupancy in the central nervous system. The action of vortioxetine was compared to the action of equal doses of the serotonin-noradrenaline reuptake inhibitor, venlafaxine (one of the gold standard drugs in the treatment of neuropathic pain), and fluoxetine. Vortioxetine caused a robust analgesia in chronic constriction injury mice, and its effect was identical to that produced by venlafaxine. In contrast, fluoxetine was inactive in chronic constriction injury mice. Vortioxetine enhanced mechanical pain thresholds in chronic constriction injury mice without changing motor activity, as assessed by the open-field and horizontal bar tests. None of the three antidepressants caused analgesia in the complete Freund's adjuvant model of chronic inflammatory pain. These findings raise the attractive possibility that vortioxetine can be effective in the treatment of neuropathic pain, particularly in patients with comorbid depression and cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Objective: To determine the diagnostic performance of two-dimensional (2D) ultrasound parameters, three-dimensional (3D) power Doppler and contrast-enhanced indices in detecting residual disease in locally advanced cervical cancer patients triaged to neoadjuvant treatment followed by radical surgery.Methods: Between October 2010 and June 2014, we screened 108 women with histologically documented locally advanced cervical cancer Stage IB2-IVA, of whom 88 were included in the final analysis. 2D ultrasound parameters, 3D power Doppler and contrast-ultrasound parameters were assessed 5 weeks after the end of neoadjuvant chemoradiation therapy. The pathological response was defined as complete (absence of any residual tumor after treatment) or partial (including microscopic and/or macroscopic residual tumor at pathology examination). The two response groups were compared and receiver-operating characteristics (ROC) curves generated to determine the best cut-off value of sonographic tumor diameter to predict residual disease. Histology was considered as reference.Results: Complete pathological response to chemoradiation was observed in 40 (45.5%) patients and partial response in 48 (54.5%). The presence of residual disease, as confirmed at pathology examination, was detected by 2D grayscale ultrasound with a sensitivity of 64.6% and specificity of 65%. Color Doppler examination in the cases with lesions visualized on grayscale imaging detected the presence of residual disease, confirmed at pathology, with a sensitivity of 87.1% and specificity of 21.4%. The best area under the ROC curve (0.817) was for the detection of pathological residual disease of at least 6 mm in diameter, using a cut-off value of 12 mm for the largest tumor diameter assessed using 2D grayscale ultrasound (sensitivity, 95%; specificity, 70.6%). Neither 3D vascular indices nor contrast-ultrasound parameters obtained for lesions suspected at ultrasound following chemoradiation differed significantly between patients with histological complete and those with partial response.Conclusions: Our results show that grayscale and color Doppler ultrasound have a low level of diagnostic performance in detecting residual disease after neoadjuvant chemoradiation in patients with locally advanced cervical cancer. The best performance was achieved in detection of macroscopic (≥ 6 mm) residual disease. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Aim: To characterize the phenotypic profile of a cohort of children affected with CLN5, a rare form of neuronal ceroid-lipofuscinosis (NCL), and to trace the features of the natural history of the disease.Method: Records of 15 children (nine males, six females) were obtained from the data sets of the DEM-CHILD International NCL Registry. Disease progression was measured by rating six functional domains at different time points along the disease course. All patients underwent mutation analysis of the CLN5 gene and ultrastructural investigations of peripheral tissues. Expression of the gene product, pCLN5, was characterized in vitro in six patients.Results: Disease onset was at 2 to 7 years 6 months of age: impaired learning and cognition were the most common early symptoms. Seizures occurred relatively late (median age 8y) and were the presenting symptoms in two children. Nine mutations were detected in 30 alleles, including six mutations predicting a truncated protein. Mixed cytosomes were observed by electron microscopy. Differences of disease progression were observed in two groups of patients and could be related to their genetic profile.Interpretation: Clinical features in a multicentre cohort of patients with CLN5 confirm that cognitive difficulties are early clinical markers of this condition. Severe mutations were associated with a more rapid decline of neurological function. [ABSTRACT FROM AUTHOR]

Purpose: Cystadenofibroma (CAF) is a rare tumour of the ovary that can be confused with a borderline or malignant lesion due to its morphological characteristics. The study aims to analyse the MRI (magnetic resonance imaging) features of histologically proven ovarian cystadenofibromas according to lexicon-based and O-RADS (Ovarian-Adnexal Reporting and Data System) descriptors, with particular attention to time-intensity curves (TIC) and Diffusion-Weighted sequences (DWI); we also wanted to test the performance of O-RADS MRI risk stratification system in this particular subgroup of patients.Methods: We have included all patients who performed MR between October 2019 and December 2021 after an inconclusive trans-vaginal ultrasound. All patients underwent surgery with histological results of CAF. According to the O-RADS lexicon, we reported the morphological characteristics of each lesion and their appearance in the perfusion-weighted imaging (PWI) and DWI sequences. We assessed the risk of malignancy for each lesion through O-RADS MRI score.Results: Twenty-one histologically proven CAF were analysed, of which 20 benign and one borderline with degeneration into adenocarcinoma. We described the typical morphological characteristics of CAF according to lexicon-based and O-RADS descriptors. Analysis of time-intensity curves (TIC) in PWI sequences showed a slow and progressive enhancement of solid tissue (type I curve), configuring an O-RADS score of 2 or 3, except for the only malignant lesion that showed a type II curve and restriction in DWI (O-RADS 4).Conclusions: Our study is the largest comprising PWI and DWI sequences, highlighting their pivotal role. O-RADS score correctly classified the masses as benign or malignant. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses a case study of a female child with infantile neuronal ceroid lipofuscinosis (CLN10 disease) associated with mutation in cathepsin D (CTSD).

Background With a complex and extremely high clinical and genetic heterogeneity, autism spectrum disorders (ASD) are better dissected if one takes into account specific endophenotypes. Comorbidity of ASD with epilepsy (or paroxysmal EEG) has long been described and seems to have strong genetic background. Macrocephaly also represents a well-known endophenotype in subgroups of ASD individuals, which suggests pathogenic mechanisms accelerating brain growth in early development and predisposing to the disorder. We attempted to estimate the association of gene variants with neurodevelopmental disorders in patients with autism-epilepsy phenotype (AEP) and cranial overgrowth, analyzing two genes previously reported to be associated with autism and macrocephaly. Methods We analyzed the coding sequences and exon-intron boundaries of GLIALCAM, encoding an IgG-like cell adhesion protein, in 81 individuals with Autism Spectrum Disorders, either with or without comorbid epilepsy, paroxysmal EEG and/or macrocephaly, and the PTEN gene in the subsample with macrocephaly. Results Among 81 individuals with ASD, 31 had concurrent macrocephaly. Head circumference, moreover, was over the 99.7th percentile ("extreme" macrocephaly) in 6/31 (19%) patients. Whilst we detected in GLIALCAM several single nucleotide variants without clear pathogenic effects, we found a novel PTEN heterozygous frameshift mutation in one case with "extreme" macrocephaly, autism, intellectual disability and seizures. Conclusions We did not find a clear association between GLIALCAM mutations and AEP-macrocephaly comorbidity. The identification of a novel frameshift variant of PTEN in a patient with "extreme" macrocephaly, autism, intellectual disability and seizures, confirms this gene as a major candidate in the ASD-macrocephaly endophenotype. The concurrence of epilepsy in the same patient also suggests that PTEN, and the downstream signaling pathway, might deserve to be investigated in autism-epilepsy comorbidity. Working on clinical endophenotypes might be of help to address genetic studies and establish actual causative correlations in autism-epilepsy. [ABSTRACT FROM AUTHOR]

Cerebellar cysts are rare findings in pediatric neuroimaging and rather characteristic for dystroglycanopathies and GPR56-related encephalopathy. We aim to report on seven children with cerebellar cysts showing absence of weakness and ruling out mutations within eight dystroglycanopathy genes and GPR56. Data about neurological and ophthalmological features, outcome, and creatine kinase values were collected from clinical histories and follow-up examinations. All MR images were qualitatively evaluated for infra- and supratentorial abnormalities. A SNP 6.0-Array was performed in three children. The POMT1, POMT2, POMGnT1, FKRP, FKTN, LARGE, ISPD, B3GALNT2, and GPR56 genes were screened in all patients by Sanger sequencing. Seven children from five families were studied. Ataxia, intellectual disability, and language impairment were found in all patients, ocular motor apraxia in five, and severe myopia in three. None of the patients had weakness, only three a minimally increased creatine kinase value. Qualitative neuroimaging evaluation showed cerebellar cysts and dysplasia in the cerebellar hemispheres and vermis in all children. Additional findings were an enlarged fourth ventricle in all children, vermian hypoplasia and brain stem morphological abnormalities in five. The SNP array showed no pathogenetic imbalances in all children evaluated. In all patients, no mutations were found in POMT1, POMT2, POMGnT1, FKRP, FKTN, LARGE, ISPD, B3GALNT2, and GPR56. The peculiar combination of the same clinical and neuroimaging findings in our patients highly suggests that this phenotype may represent a novel entity, possibly falling within the spectrum of dystroglycanopathies. [ABSTRACT FROM AUTHOR]

Summary Objective The objective of this study is to determine the ability of metformin treatment in reducing the prevalence of metabolic syndrome (MS) and its hepatic involvement in young hyperinsulinaemic overweight patients with polycystic ovarian syndrome (PCOS). Design Clinical Trial. Patients We recruited 140 hyperinsulinaemic overweight women with PCOS in their reproductive age. Metformin treatment (500 mg × 3/die) was prescribed to each patient for twelve months. Measurements The primary outcome was to evaluate the prevalence of nonalcoholic fatty liver disease (NAFLD) and MS in hyperinsulinaemic overweight patients with PCOS. The secondary outcome was to evaluate, in the same patients, the effects of metformin therapy on endocrine, metabolic and hepatic parameters. Results At basal evaluation, NAFLD was diagnosed in 81 of 140 patients with PCOS (57·85%); MS was present only in the NAFLD group (32·09% vs 0%; P < 0·001). After twelve months, metformin is able to significantly reduce, in the same group, the prevalence of MS (28·9% vs 13·5%; P < 0·01). An improvement of hepatic parameters and a significant decrease in oligomenorrhea (85·7% vs 19%, P < 0·001) were also observed. Conclusions Treatment with metformin is indicated in all hyperinsulinaemic overweight patients with PCOS, especially in those with NAFLD. These data appear even more interesting considering their increased risk to develop metabolic and hepatic complications. [ABSTRACT FROM AUTHOR]

Postconditioning (PostC) modifies the early post-ischemic pH, redox environment, and activity of enzymes. We hypothesized that early acidosis in PostC may affect superoxide dismutase (SOD) and catalase (CAT) activities, may reduce 3-nitrotyrosine (3-NT) protein levels, and may increase S-nitrosylated (SNO) protein levels, thus deploying its protective effects. To verify this hypothesis, we studied the early (7 min) and late (120 min) phases of reperfusion (a) endogenous SOD and CAT activities and (b) 3-NT protein levels and SNO protein levels. Isolated rat hearts underwent 30-min ischemia/120-min reperfusion (I/R) or PostC (5 cycles of 10-s I/R at the beginning of 120-min reperfusion) either with or without exogenous CAT or SOD infused during the initial 3 min of reperfusion. The effects of early reperfusion with acid buffer (AB, pH 6.8) on endogenous antioxidant enzymes were also tested. Pressure, infarct size, and lactate dehydrogenase release were also measured. At the 7 min, PostC induced a significant decrease in SOD activity with no major change both in Mn and Cu/Zn SOD levels and in CAT activity and level. PostC also reduced 3-NT and increased SNO levels. Exogenous SOD, but not CAT, abolished PostC cardioprotection. In late reperfusion (120-min), I/R increased SOD activity but decreased CAT activity and Cu/Zn SOD levels; these effects were reversed by PostC; 3-NT was not affected, but SNO was increased by PostC. AB reproduced PostC effects on antioxidant enzymes. The conclusions are as follows: PostC downregulates endogenous SOD and preserves CAT activity, thus increasing SNO and reducing 3-NT levels. These effects are triggered by early post-ischemic acidosis. Yet acidosis-induced SOD downregulation may limit denitrosylation, thus contributing to PostC triggering. Hence, exogenous SOD, but not CAT, interferes with PostC triggering. Prolonged SOD downregulation and SNO increase may contribute to PostC and AB beneficial effects. [ABSTRACT FROM AUTHOR]

Abstract: The inwardly-rectifying potassium channel Kir4.1 is a major player in the astrocyte-mediated regulation of [K+]o in the brain, which is essential for normal neuronal activity and synaptic functioning. KCNJ10, encoding Kir4.1, has been recently linked to seizure susceptibility in humans and mice, and is a possible candidate gene for Autism Spectrum Disorders (ASD). In this study, we performed a mutational screening of KCNJ10 in 52 patients with epilepsy of “unknown cause” associated with impairment of either cognitive or communicative abilities, or both. Among them, 14 patients fitted the diagnostic criteria for ASD. We identified two heterozygous KCNJ10 mutations (p.R18Q and p.V84M) in three children (two unrelated families) with seizures, ASD, and intellectual disability. The mutations replaced amino acid residues that are highly conserved throughout evolution and were undetected in about 500 healthy chromosomes. The effects of mutations on channel activity were functionally assayed using a heterologous expression system. These studies indicated that the molecular mechanism contributing to the disorder relates to an increase in either surface-expression or conductance of the Kir4.1 channel. Unlike previous syndromic associations of genetic variants in KCNJ10, the pure neuropsychiatric phenotype in our patients suggests that the new mutations affect K+ homeostasis mainly in the brain, by acting through gain-of-function defects. Dysfunction in astrocytic-dependent K+ buffering may contribute to autism/epilepsy phenotype, by altering neuronal excitability and synaptic function, and may represent a new target for novel therapeutic approaches. [Copyright &y& Elsevier]

Women affected by polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease. We demonstrated that women with PCOS showed an expansion of CD4+CD28null T cells, an aggressive population of T lymphocytes that has been recently associated with recurrent coronary instability and type 2 diabetes mellitus. This sheds new light on possible mechanisms responsible for the higher rate of cardiovascular disease among women with PCOS. [ABSTRACT FROM AUTHOR]

The dystroglycanopathies, which are caused by reduced glycosylation of alpha-dystroglycan, are a heterogeneous group of neurodegenerative disorders characterized by variable brain and skeletal muscle involvement. Recently, mutations in TMEM5 have been described in severe dystroglycanopathies. We present the clinical, molecular and neuroimaging features of an Italian boy who had delayed developmental milestones with mild limb-girdle muscle involvement, bilateral frontotemporal polymicrogyria, moderate intellectual disability, and no cerebellar involvement. He also presented a cochlear dysplasia and harbored a reported mutation (p.A47Rfs*42) in TMEM5 , detected using targeted next-generation sequencing. The relatively milder muscular phenotype and associated structural brain abnormalities distinguish this case from previously reported patients with severe dystroglycanopathies and expand the spectrum of TMEM5 -associated disorders. [ABSTRACT FROM AUTHOR]

Abstract: Postconditioning (PostC) may limit mitochondrial damage and apoptotic signaling. We studied markers of apoptosis and mitochondrial protection in isolated rat hearts, which underwent a) perfusion without ischemia (Sham), b) 30-min ischemia (I) plus 2-hour reperfusion (R), or c) PostC protocol (5 intermittent cycles of 10-s reperfusion and 10-s ischemia immediately after the 30-min ischemia). Markers were studied in cytosolic (CF) and/or mitochondrial (MF) fractions. In CF, while pro-apoptotic factors (cytochrome c and caspase-3) were reduced, the anti-apoptotic markers (Bcl-2 and Pim-1) were increased by PostC, compared to the I/R group. Accordingly, phospho-GSK-3β and Bcl-2 levels increased in mitochondria of PostC group. Moreover, I/R reduced the level of mitochondrial structural protein (HSP-60) in MF and increased in CF, thus suggesting mitochondrial damage and HSP-60 release in cytosol, which were prevented by PostC. Electron microscopy confirmed that I/R markedly damaged cristae and mitochondrial membranes; damage was markedly reduced by PostC. Finally, total connexin-43 (Cx43) levels were reduced in the CF of the I/R group, whereas phospho-Cx43 level resulted in higher levels in the MF of the I/R group than the Sham group. PostC limited the I/R-induced increase of mitochondrial phospho-Cx43. Data suggest that PostC i) increases the levels of anti-apoptotic markers, including the cardioprotective kinase Pim-1, ii) decreases the pro-apoptotic markers, e.g. cytochrome c, iii) preserves the mitochondrial structure, and iv) limits the migration of phospho-Cx43 to mitochondria. [Copyright &y& Elsevier]

Whether cardioprotection by postconditioning (PostC) is gender dependent is not clear. We studied the effect of PostC in terms of both infarct size (IS) and post-ischemic systolic dysfunction (PSD) reduction. Isolated male and female rat hearts were subjected to 10- or 30-min of global ischemia and 120-min of reperfusion, with or without PostC (i.e., 5 cycles of 10-s reperfusion/ischemia immediately after the ischemia). Surprisingly, after 10-min ischemia, IS and PSD were greater in female than male hearts (IS: 21 ± 2% Vs. 11 ± 2%; P < 0.01), while PostC attenuated IS and PSD in female hearts only. After 30-min ischemia IS was smaller in female than male hearts (52 ± 2% Vs. 61 ± 3%; P < 0.05), whereas PSD was similar in these two groups. PostC reduced IS in both genders, though the effect was smaller ( P < 0.05) in females. Yet, PostC reduced PSD in female, but not in male hearts. Contracture development paralleled IS in all groups. To check the effects of buffer perfusion over heart function, additional hearts underwent 150-min buffer perfusion only. Contractile function of these hearts was not significantly affected over time. In conclusion IS, contracture and PSD are differently affected by gender, depending on ischemia duration. Yet, reduction of IS induced by PostC depends on the extension of IS induced by index-ischemia. While in female hearts reduction of PSD paralleled IS reduction, in male it does not occur. Results suggest that improvement of systolic function is mainly due to the anti-necrotic rather than to the anti-stunning effect exerted by PostC. [ABSTRACT FROM AUTHOR]

Purpose:Autosomal dominant lateral temporal lobe epilepsy (ADLTLE) is a rare familial epilepsy with onset in adolescence or early adulthood, associated with mutations ofLGI1in most families. We describe the clinical, neuropsychological, and molecular genetic study of a new ADLTLE Italian family.Methods:A four-generation family from Sardinia was studied. Clinical, neuropsychological, and genetic analysis were performed in eight living affected family members.Results:Nine family members had seizures over four generations; four of them had auditory auras and aphasia followed by secondarily generalized tonic–clonic seizures (SGTCs). One individual in addition had visual symptoms, and one family member had only vertigo followed by SGTCs. The side of seizure onset could not be determined in these five patients with focal seizures. The proband had febrile and afebrile tonic–clonic seizures. Two family members had only febrile seizures. Inheritance was autosomal dominant with 59% penetrance. Genetic molecular analysis showed a newLGI1missense mutation causing a Leu154Pro substitution in six affected and one unaffected individuals. Dichotic listening performance was abnormal in four affected individuals compared with controls. Fluency and lexical abilities also were pathological in three patients. These findings showed that in patients, the left temporal lobe was less specialized in the auditory processing function than in controls.Conclusions:In this ADLTLE family, both seizure semiology and neuropsychological findings point to a lateral temporal lobe dysfunction. The newly identifiedLGI1mutation might underlie both the seizure disorder and the neuropsychological deficits. [ABSTRACT FROM AUTHOR]