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Placental alterations caused by severe acute respiratory coronavirus-2 (SARS-CoV-2) infection have already been described, but most studies used small sample groups and the difference according to the severity of the disease has not been verified. Our objective was to describe placental alterations in patients with coronavirus disease 2019 (COVID-19) and analyze the association of pathological placental findings with the clinical parameters of COVID-19 and perinatal results.This was a nested study within a prospective cohort study involving 109 symptomatic pregnant women with COVID-19. The prevalence of observed placental alterations was described, and the associations of pathological findings with the clinical parameters of COVID-19 severity and with perinatal outcomes were assessed.The frequency of types of placental features was poor maternal vascular perfusion in 45% of cases, poor fetal vascular perfusion in 33.9%, hematogenous origin infection in 32.1%, and morphological changes corresponding to ascending infection in 21.1%. Hematogenous infection differed significantly according to COVID-19 severity (p = 0.008), with a prevalence ratio (PR) of 1.74 (95% confidence interval, 1.02-2.98) in the moderate COVID-19 group compared to the mild COVID-19 group. Among the perinatal outcomes, there was an unexpected inverse association between prematurity and placental infection of hematogenous origin, with lower rates of prematurity among cases with inflammation of hematogenous origin (p = 0.029).Moderate SARS-Cov-2 infection presented a higher prevalence of placental pathological findings. There was no association of placental findings with adverse perinatal outcomes.

Introduction. Controlling the invasive activity of trophoblastic tissue has not been elucidated. In the accreta placenta, the invasion of placental tissue is directly related to the expression of CRIPTO-1 at the maternal-fetal interface. The aim of this study is to evaluate if the expression of the CRIPTO-1 is related to different degrees of trophoblast invasion into the tube wall in ampullary pregnancy. Methods. Prospective study with 21 patients with ampullary tubal pregnancy undergoing salpingectomy. Anatomopathological evaluation determined the degree of invasion of trophoblast tissues into the tubal wall and grouped the samples into invasive degrees I, II, or III. The groups were compared for tissue expression of CRIPTO-1 using the Kruskal-Wallis nonparametric test. p values lower than 0.05 were considered significant. Results. Quantitative expression of CRIPTO-1 differed in each of the three groups of trophoblast invasion in the tubal wall in ampullary pregnancies ( p < 0.001 ). There is a difference between groups when grade I + grade II versus grade III ( p < 0.001 ) and grade I versus grade II + grade III ( p < 0.001 ). The tissue expression of CRIPTO-1 in ectopic trophoblasts showed that deeper invasion of the tubal wall was associated with stronger expression than in shallow invasion ( p < 0.001 ). Discussion. In ampullary pregnancies, the depth of penetration of trophoblast tissue in the tubal wall is related to CRIPTO-1 tissue expression.

ObjectiveChronic pain is a prevalent and burdensome condition. Reboot Online was developed to address treatment barriers traditionally associated with accessing face-to-face chronic pain management programs. It is a comprehensive multidisciplinary online treatment program, based on an existing and effective face-to-face multidisciplinary pain program (the Reboot program).Design & ParticipantsA CONSORT-compliant randomized controlled trial was conducted, enrolling adults who had experienced pain for three months or longer.MethodsParticipants were randomly allocated to either an eight-lesson multidisciplinary pain management program, Reboot Online (N = 41), or to a usual care (UC) control group (N = 39). Clinical oversight was provided by a multidisciplinary team remotely, including physiotherapists and clinical psychologists. Participants were measured at baseline, post-treatment (week 16), and three-month follow-up (week 28).ResultsIntention-to-treat analyses revealed that Reboot Online was significantly more effective than UC at increasing pain self-efficacy (g = 0.69) at post-treatment, and these gains were maintained at follow-up. Similarly, Reboot Online was significantly more effective than UC on several secondary measures at post-treatment and follow-up, including movement-based fear avoidance and pain-related disability, but it did not significantly reduce pain interference or depression compared with UC. Clinician input was minimal, and adherence to Reboot Online was moderate, with 61% of participants (N = 25) completing all eight lessons.ConclusionsReboot Online presents a novel approach to multidisciplinary pain management and offers an accessible, efficacious alternative and viable treatment option for chronic pain management.

BACKGROUND Internet-based treatment programs present a solution for providing access to pain management for those unable to access clinic-based multidisciplinary pain programs. Attrition from internet interventions is a common issue. Clinician-supported guidance can be an important feature in web-based interventions; however, the optimal level of therapist guidance and expertise required to improve adherence remains unclear. OBJECTIVE The aim of this study is to evaluate whether augmenting the existing Reboot Online program with telephone support by a clinician improves program adherence and effectiveness compared with the web-based program alone. METHODS A 2-armed, CONSORT (Consolidated Standards of Reporting Trials)–compliant, registered randomized controlled trial with one-to-one group allocation was conducted. It compared a web-based multidisciplinary pain management program, Reboot Online, combined with telephone support (n=44) with Reboot Online alone (n=45) as the control group. Participants were recruited through web-based social media and the This Way Up service provider network. The primary outcome for this study was adherence to the Reboot Online program. Adherence was quantified through three metrics: completion of the program, the number of participants who enrolled into the program, and the number of participants who commenced the program. Data on adherence were collected automatically through the This Way Up platform. Secondary measures of clinical effectiveness were also collected. RESULTS Reboot Online combined with telephone support had a positive effect on enrollment and commencement of the program compared with Reboot Online without telephone support. Significantly more participants from the Reboot Online plus telephone support group enrolled (41/44, 93%) into the course than those from the control group (35/45, 78%; χ21=4.2; P=.04). Furthermore, more participants from the intervention group commenced the course than those from the control group (40/44, 91% vs 27/45, 60%, respectively; χ21=11.4; P=.001). Of the participants enrolled in the intervention group, 43% (19/44) completed the course, and of those in the control group, 31% (14/45) completed the course. When considering the subgroup of those who commenced the program, there was no significant difference between the proportions of people who completed all 8 lessons in the intervention (19/40, 48%) and control groups (14/27, 52%; χ21=1.3; P=.24). The treatment efficacy on clinical outcome measures did not differ between the intervention and control groups. CONCLUSIONS Telephone support improves participants’ registration, program commencement, and engagement in the early phase of the internet intervention; however, it did not seem to have an impact on overall course completion or efficacy. CLINICALTRIAL Australian New Zealand Clinical Trials Registry ACTRN12619001076167; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12619001076167

Objective Chronic pain is a prevalent and disabling condition. Reboot Online was developed as a multidisciplinary and widely accessible online treatment program for chronic pain. It has been shown to be effective in clinical trials, but the effectiveness of this program in routine care settings remains unknown. This study aimed to examine program adherence and effectiveness in a real-world sample of participants completing Reboot Online in the community. Design and subjects A retrospective cohort study was conducted using real-world data from participants referred the Reboot Online program by clinicians as part of their routine care, from April 2017 to April 2019. Methods Routinely collected data on program adherence, participant demography and clinical outcomes were included in the analyses. Measures included the Pain Self Efficacy Questionnaire, Brief Pain Inventory, Tampa Scale of Kinesiophobia, Pain-Disability Index, and Patient Health Questionnaire 9-item (depression). Logistic regression was used to investigate whether certain factors predict program adherence (completion versus noncompletion), and linear mixed models were used to examine effectiveness. Results In total, 867 participants were included in the analyses, and 583 engaged with at least one Reboot Online lesson. Of these, 42% (n = 247) completed the course in its entirety, with rurality and lower Tampa scores being significant predictors of adherence. Completers demonstrated significant improvements across all outcome measures (effect sizes ranging from 0.22 to 0.51). Conclusions Reboot Online is an effective treatment for chronic pain in the routine care setting. Adherence was variable (overall 42%), and could be predicted by rurality and less fear of movement at baseline.

Neuropsychologists are commonly asked practical questions about cognitive recovery in the first year following moderate-to-severe traumatic brain injury (TBI), however guiding evidence to provide answers is limited. The design of this longitudinal study rectifies methodological problems in the literature by taking serial assessments on a monthly basis from 3- to 12-months post-trauma in a severe TBI sample (

Objective This study investigated the qualitative and semi-quantitative expression of metalloproteinases (MMP) and their tissue inhibitors (TIMP) in trophoblastic tissue during ampullary ectopic pregnancies and correlated that expression with the degree of tubal invasion. Study design It is a prospective study that included 34 patients diagnosed with ampullary tubal pregnancy who underwent salpingectomy. A histological evaluation of the depth of trophoblastic invasion in the tubes obtained was performed. Subsequently, the expression of the MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2 and TIMP-3 markers was qualitatively and semi-quantitatively evaluated by indirect immunohistochemistry. In addition, the degree of trophoblastic invasion was correlated with the expression of each marker and with the metalloproteinase/inhibitor ratios. Results MMP-2 (11.2 %; 3.6–17.9) was the marker with greater expression at the implantation site, both in the qualitative and semi-quantitative assessment, while MMP-9 (2.23 %; 0.2–5.4) and TIMP-3 (2.53 %; 0.1–15.3) were only weakly expressed. Conclusion There was wide variation in expression among the markers and metalloproteinase/inhibitor ratios studied compared to the degrees of invasion.

Both partial mole and twin gestation are conditions associated with the risk of the early onset of pre‐eclampsia. In cases of twin gestation, the death or selective termination of a severely growth‐restricted fetus may lead to the reversal of maternal pre‐eclampsia because of the involution or death of the pathological placenta, as has been reported by some authors. This case demonstrates that in a twin triploid gestation, in spite of the demise of one of the fetuses, the respective partial molar placenta can continue to grow and may contribute to the development or to the worsening of the pre‐eclampsia.

OBJECTIVES: To assess the expression of decidual natural killer (dNK) cells and their cytokines in twin pregnancies with preeclampsia. METHODS: This was a prospective case-control study. The inclusion criteria were diamniotic (monochorionic or dichorionic) twin pregnancies in the third trimester with negative serological results for infectious diseases; absence of major fetal abnormalities or twin-twin transfusion syndrome; and no history of administration of corticosteroids in this pregnancy. The control group (CG) included uncomplicated twin pregnancies, and the preeclampsia group (PEG) included twin gestations with clinical and laboratory confirmation of the disease according to well-established criteria. Samples of the decidua were obtained and analyzed by immunohistochemistry for the expression of dNK cells and interleukins (ILs) 10, 12 and 15. In addition, maternal serum samples were collected to determine the levels of these interleukins. RESULTS: Thirty twin pregnancies were selected: 20 in the control group (CG) and 10 in the preeclampsia group (PEG). The PEG showed strong placental immunostaining for IL-15 (p=0.001) and high maternal serum levels of IL-10 (22.7 vs. 11.9 pg/mL, p=0.024) and IL-15 (15.9 vs. 7.4 pg/mL, p=0.024). CONCLUSION: A higher maternal serum concentration of both pro- and anti-inflammatory factors was observed in the twin pregnancies in the PEG. However, no difference in placental expression of IL-10 was found between the groups. These findings may suggest that maternal attempts to balance these interleukins were not sufficient to cause a placental response, and this failure may contribute to the development of preeclampsia.

OBJECTIVE: The aim of the present study was to compare the placental weight and birth weight/placental weight ratio for intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. METHODS: This was a retrospective analysis of placentas from twin pregnancies. Placental weight and the birth weight/placental weight ratio were compared in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. The association between cord insertion type and placental lesions in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins was also investigated. RESULTS: A total of 105 monochorionic (intrauterine growth restriction=40; non-intrauterine growth restriction=65) and 219 dichorionic (intrauterine growth restriction=57; non-intrauterine growth restriction=162) placentas were analyzed. A significantly lower placental weight was observed in intrauterine growth-restricted monochorionic (p=0.022) and dichorionic (p

OBJECTIVE: To evaluate the association between the depth of trophoblastic infiltration and serum vascular endothelial growth factorconcentration in patients with an ampullary pregnancy. METHODS: This prospective cross-sectionalstudy involved 34 patients with an ampullary ectopic pregnancy who underwent salpingectomy between 2012 and 2013. Maternal serum vascular endothelial growth factor concentrations were measured using Luminex technology. Trophoblastic invasion was classified histologically as follows: stage I, limited to the tubal mucosa; stage II, reaching the muscle layer; and stage III,involving the full thickness. The qualitative data were compared using Fisher's exact test. The nonparametric Kruskal-Wallis and Mann-Whitney tests were used to evaluate differences in serum vascular endothelial growth factor among the degrees of trophoblastic invasion. ROC curves were constructed to determine vascular endothelial growth factor cut-off values that predict the degree of tubal invasion based on the best sensitivity and specificity. RESULTS: Eight patients had stage I trophoblastic invasion, seven had stage II, and 19 had stage III. The median serum vascular endothelial growth factorconcentration was 69.88 pg/mL for stage I, 14.53 pg/mL for stage II and 9.08 pg/mL for stage III, with a significant difference between stages I and III. Based on the ROC curve, a serum vascular endothelial growth factor concentration of 25.9 pg/mL best differentiated stage I from stages II and III with asensitivity of 75.0%, specificity of 76.9%, and area under the curve of 0.798. CONCLUSIONS: The depth of trophoblastic penetration into the tubal wall isassociated with serum vascular endothelial growth factor concentration in ampullary pregnancies.

Congenital cystic adenomatoid malformation (CCAM) is an hamartomatous congenital pulmonary airway malformation with incidence ranging between 1:10,000 and 1:35,000 newborns. Currently CCAM is classified into five groups according to clinical and pathological features. The clinical outcome varies depending on the subtype and the extent of involvement. The authors report the case of a premature male newborn with the prenatal diagnosis of CCAM Type 1 associated with cardiac right axis deviation, who died 67 hours after birth due to respiratory failure. In addition to the autopsy report of this rare entity, the authors present its classification and prognosis.

Objective To assess the association between ultrasound images and serum concentrations of vascular endothelial growth factor (VEGF) in ampullary pregnancies. Design Prospective study. Setting University hospital. Patient(s) Fifty patients with ampullary pregnancy. Intervention(s) Criteria for inclusion in the study were: singleton pregnancy from spontaneous conception; diagnosis of tubal pregnancy in the ampullary region; radical surgical treatment (salpingectomy); and measurement of serum VEGF, human chorionic gonadotropin, and progesterone on the day of surgery. An additional criterion was description of an ectopic mass by transvaginal ultrasound, as follows: [1] ectopic gestational sac containing an embryo with cardiac activity; and [2] tubal ring: a paraovarian formation similar to a gestational sac, not containing a viable embryo (an anechoic structure surrounded by a peripheral hyperechogenic halo); an empty ectopic gestational sac; a sac containing an embryo without cardiac activity; or a vitelline vesicle. Main Outcome Measure(s) Association between ultrasound images and serum concentrations of VEGF. Result(s) An association was found between ultrasonographic images and VEGF serum concentrations. Ectopic embryos with cardiac activity were associated with higher levels of serum VEGF. Conclusion(s) In ampullary pregnancy, higher serum levels of VEGF are associated with the finding of an embryo with cardiac activity on transvaginal ultrasound. Greater production of VEGF likely creates development conditions more conducive to ectopic embryos.

Introducao A displasia arritmogenica do ventriculo direito (DAVD) e um disturbio do musculo cardiaco que se caracteriza patologicamente pela substituicao fibrotica do miocardio ventricular direito (e as vezes esquerdo). Em 30-90% dos casos, e uma condicao hereditaria com uma forma de transmissao autossomica dominante. E com expressao variavel. Nesse artigo, discutimos um caso raro de DAVD fetal e seu dificil diagnostico pre-natal, apenas confirmado na autopsia pos-natal. […] Um Caso de Displasia Arritmogenica do Ventriculo Direito Pre-natal

Objectives. Chronic pain causes significant disability and psychological distress, but barriers often prevent people with pain from engaging in traditional face-to-face pain management programs. Accessible, feasible, and effective alternative treatment options are needed. Methods. A prospective, feasibility pilot study was conducted to trial a novel, multidisciplinary online pain management program: the “Reboot Online” program. Twenty participants experiencing pain of at least three months duration were recruited. All participants were enrolled in the “Reboot Online” program, consisting of eight online lessons completed over 16 weeks. Lessons incorporated multidisciplinary input from medical pain specialists, physiotherapists, and psychologists. Participants were assessed at pretreatment, posttreatment, and follow-up using a suite of outcome measures examining pain, disability, catastrophising, self-efficacy, mood, and psychological distress. Results. 13 participants completed the program (65% adherence). Following treatment, the participants had significantly improved scores on measures of pain-related disability, self-efficacy, catastrophising thoughts, acceptance of pain, symptoms of depression, and general psychological distress. These findings were retained at three months posttreatment. Participants also reported high levels of acceptability and satisfaction with the program. Discussion. This study provides pilot evidence for the feasibility, acceptability, and effectiveness of an online, multidisciplinary pain program: “Reboot Online.” Future investigations will focus on conducting a randomised controlled trial of this innovative and promising treatment for chronic pain. This trial is registered with ACTRN12615000660583.

Firstly described by Rudolf Virchow in the 19th century, congenital generalized lymphangiectasia is a rare entity characterized by dilation of lymphatic vessels, and was recently classified in primary or secondary lymphangiectasia. Generalized forms may be diagnosed during pre-natal follow-up with ultrasound examination, and, depending on its severity, the newborn outcome is very poor. The authors report the case of a female newborn with a previous diagnosis of fetal hydropsy who was born after a full-term gestation with respiratory failure due to bilateral voluminous pleural effusion and ascites. Physical examination also disclosed syndromic facies. Despite all efforts of the intensive supportive care, the patient died after 24 days of life. The autopsy findings were consistent with the diagnosis of congenital pulmonary lymphangiectasia. The authors call attention to this rare diagnosis in patients with cavitary effusion and respiratory insufficiency at birth.

Pompe disease (PD) is a rare, inherited autosomal recessive metabolic disorder caused by the deficiency of the lysosomal acid alpha-glucosidase (GAA) enzyme described in 1932 by the Dutch pathologist Joannes Cassianus Pompe. The prevalence of PD ranges from 1:40,000 to 1:300,000 births and depends on geographic and ethnic factors. Clinical manifestations may vary from a rapidly progressive disabling disease with cardiomegaly, hepatomegaly, weakness, generalized hypotonia, and death within the first year of life, to a mild presentation characterized by slowly progressive myopathy predominantly involving the skeletal muscles. The laboratory diagnostic gold standard is represented by the determination of the alpha-glucosidase activity. However, the muscle histology may also yield the diagnosis by evaluating the tissular glycogen accumulation. Until recently, supportive measures constituted the unique available therapy. Currently, the administration of the recombinant GAA is being used with promising results. The authors present the case of a 5-month-old boy, previously diagnosed with hypertrophic cardiomyopathy since the age of 2 months, who presented acute heart failure accompanied by biventricular dilation followed by refractory shock and death. The autopsy findings confirmed the glycogen-accumulation disease.

Placental mesenchymal dysplasia (PMD) is a rare placental disorder characterized by placental enlargement and areas of abnormal, enlarged, grape-like villi. This condition may resemble a partial hydatidiform mole and may occur associated with Beckwith–Wiedemann syndrome (BWS) or in phenotypically normal fetuses. There were 110 cases reported so far. We describe one case with typical gross and microscopic placental lesions.

Thanatophoric dysplasia (TD) is one of the most common lethal skeletal dysplasias, which was first designated as thanatophoric dwarfism and described in 1967. The authors report a case of a Caucasian girl with TD, born to a 31-year-old woman without comorbidities. The newborn presented respiratory distress immediately after delivery, progressing to death in less than 2 hours. An autopsy was carried out after postmortem tomographic examination. The autopsy findings depicted extensive malformations of the skeletal system and the brain. The aim of this report is to discuss the pathogenesis and correlate the morphologic features of TD that were disclosed at the tomography and the autopsy.

Background: Previous research addressing cognitive recovery after traumatic brain injury (TBI) in adults has predominately used cross-sectional methods. This systematic review examines longitudinal research into cognitive recovery in the first 2 years following moderate-to-severe TBI in adults and aims to identify apparent methodological issues with the existing literature.Design: Systematic review of the first 2 years post-trauma.Setting: Data were extracted from three electronic databases and manual searches of published articles until October 2012.Participants: Two hundred and forty-two participants with severe TBI and 281 comparison participants were used to calculate effect sizes.Results: Twenty papers met the selection criteria, with effect sizes computed from four studies. Moderate-to-large effect sizes were initially observed between the TBI and comparison groups on most measures (range: d = 0.2–2.8). Recovery continued in all five cognitive domains over the 2 years post-injury.Conclusions: Results demonstrated that cognitive recovery was continuous throughout the first 2 years following moderate-to-severe TBI. Findings also indicated different rates of recovery for the specific cognitive domains, highlighting the heterogeneous nature of cognitive recovery after TBI. The review highlighted several methodological issues within the limited existing literature; recommendations were developed to improve the evidence base.

Holoprosencephaly (HPE) is a congenital defect of the brain, median structures, and face resulting from an incomplete cleavage of the primitive brain during early embryogenesis. The authors report a case of trisomy 13 syndrome diagnosed at prenatal follow up. The preterm newborn lived only 5 hours, and died because of severe respiratory failure. The autopsy findings disclosed facial, skull, limbs, cardiac, and cerebral malformations. Among the latter, the presence of alobar HPE, the central theme of this report, was evident. The most common nonrandom chromosomal abnormality in patients with HPE is trisomy 13. The most severe variant, namely alobar HPE, is shown in this case report. Discussion on this severe anomaly, along with the case report with details of Patau’s syndrome, is the goal of this report.

Self-regulation is an important prerequisite for successful academic achievement, particularly for children who are at risk for Attention Deficit Hyperactivity Disorder (ADHD). We taught Mental Contrasting with Implemen- tation Intentions (MCII), a technique that is known to facilitate the self-regulation of goal pursuit, to schoolchil- dren (sixth- and seventh-graders) both at risk and not at risk for ADHD. Parents rated their children's level of self- regulation 2 weeks after the intervention. Children at risk and not at risk benefited from MCII more than from a learning style intervention only and the benefits of MCII were particularly strong for children at risk for ADHD. The results have implications with respect to supporting chil- dren's self-regulation in their everyday school lives.

Ianez R F, Buim M E, Coutinho-Camillo C M, Schultz R, Soares F A & Lourenco S V (2010) Histopathology 57, 410–417 Human salivary gland morphogenesis: myoepithelial cell maturation assessed by immunohistochemical markers Aims: Myoepithelial cells are important components of salivary gland structure, aiding the expulsion of saliva from acinar lobules. The aim was to evaluate the expression of smooth muscle actin (SMA), calponin, caldesmon, CD10, CD29, S100 protein, glial fibrillary acidic protein (GFAP) and p63 in myoepithelial cells during salivary gland morphogenesis to understand the maturation process of these cells and their possible use in the diagnosis of salivary gland lesions. Methods and results: Major and minor human salivary glands at various stages of development, derived from fetuses at 8–26 weeks of gestation, were studied immunohistochemically. Fully developed salivary glands were used as controls. The protein p63 was present in all stages of salivary gland morphogenesis from initial bud to terminal bud stage. CD29, S100 and calponin were detected increasingly as salivary gland structure matured and in fully developed salivary gland. Proteins GFAP, CD10 and caldesmon were not observed in myoepithelial cells of salivary glands. Conclusions: The proteins SMA, calponin, CD29, S100 and p63, which are present from the earliest stages of salivary gland maturation, are valuable myoepithelial markers but, although very specific, are not exclusive markers for this cell type.

Background: This paper examines the methodological quality of aphasia therapy research using the Psychological database for Brain Impairment Treatment Efficacy (www.psycbite.com). PsycBITETM includes five designs: Systematic Reviews (SR), Randomised Controlled Trials (RCT), non‐RCTs (NRCT), Case Series (CS), and Single Subject Designs (SSD). Aim: To provide an overview of the types of research designs and levels of compliance used in aphasia treatment research studies, and assess the methodological quality of aphasia research. Methods & Procedures: A search was completed on 27 September 2007 of all papers in the target area Communication/Language/Speech on the PsycBITETM database. Papers were listed according to the methodology used and a mean methodological quality rating (MQR) score was determined for RCTs, and NRCTs based on the PEDro scale. Finally, the rate of compliance of RCTs and NRCTs for each of the criteria on the PEDro scale was analysed. Outcomes & Results: Of 339 studies indexed for aphasia:...

Background— Fetal atrioventricular (AV) block is an uncommon lesion with significant mortality. Because of the rarity of this disorder, the natural course, extensive evaluation of untreated fetuses, and late follow-up remain unclear. Methods and Results— Of the 116 consecutive cases of fetal AV block studied from 1988 to 2006, only 1 was terminated, and 75% were live births. Fifty-nine cases of AV block were associated with major structural heart disease, mainly left atrial isomerism (n=40), with only 26% of neonatal survivors. Of the 57 fetuses with normal cardiac anatomy, 41 (72%) were positive for maternal antinuclear antibodies, and 32 of these seropositive mothers did not receive any treatment. This untreated group had live-birth and 1-year infant survival rates of 93% and 90%, respectively. Five fetuses from seronegative mothers showed regression to sinus rhythm during pregnancy. The presence of major structural heart disease, hydrops, an atrial rate ≤120 bpm, and a ventricular rate ≤55 bpm were identified as risk factors for mortality. Logistic regression analysis of the whole group showed that the presence of structural heart disease was the only independent predictor of death ( P Conclusions— This long-term study confirms that fetal AV block has a poor outcome when associated with structural heart disease and that spontaneous regression of AV block is possible in seronegative forms. The survival rate of >90% of our untreated patients with isolated forms of AV block raises concerns about any decision to intervene with immunosuppressive agents.

Rating scales that assess methodological quality of clinical trials provide a means to critically appraise the literature. Scales are currently available to rate randomised and non-randomised controlled trials, but there are none that assess single-subject designs. The Single-Case Experimental Design (SCED) Scale was developed for this purpose and evaluated for reliability. Six clinical researchers who were trained and experienced in rating methodological quality of clinical trials developed the scale and participated in reliability studies. The SCED Scale is an 11-item rating scale for single-subject designs, of which 10 items are used to assess methodological quality and use of statistical analysis. The scale was developed and refined over a 3-year period. Content validity was addressed by identifying items to reduce the main sources of bias in single-case methodology as stipulated by authorities in the field, which were empirically tested against 85 published reports. Inter-rater reliability was assessed using a random sample of 20/312 single-subject reports archived in the Psychological Database of Brain Impairment Treatment Efficacy (PsycBITE). Inter-rater reliability for the total score was excellent, both for individual raters (overall ICC = 0.84; 95% confidence interval 0.73-0.92) and for consensus ratings between pairs of raters (overall ICC = 0.88; 95% confidence interval 0.78-0.95). Item reliability was fair to excellent for consensus ratings between pairs of raters (range k = 0.48 to 1.00). The results were replicated with two independent novice raters who were trained in the use of the scale (ICC = 0.88, 95% confidence interval 0.73-0.95). The SCED Scale thus provides a brief and valid evaluation of methodological quality of single-subject designs, with the total score demonstrating excellent inter-rater reliability using both individual and consensus ratings. Items from the scale can also be used as a checklist in the design, reporting and critical appraisal of single-subject designs, thereby assisting to improve standards of single-case methodology.

Background and objective Salivary gland development entails co-ordinated processes involving complex molecular interactions in which integrins have a fundamental role. The integrins are a family of heterodimeric transmembrane receptors comprising alpha and beta subunits that mediate intercellular and extracellular signals involved in the organisation of cells in tissues and organs during development. The beta-1 integrin in particular have been implicated in proliferation and differentiation of cells involved in the development of epithelial tissues. To understand the role of beta-1 integrin in salivary gland development we have studied its expression in human foetal tissues. Design In situ hybridisation was used to compare the expression and localisation of integrin beta-1 with differentiation markers in developing human salivary glands obtained from foetuses of 8–24 weeks gestation. Results Integrin beta-1 first appeared during bud stage in a few cells and its distribution increased as salivary gland morphogenesis progressed. This increased pattern of beta-1 integrin expression was coincident with the appearance of the differentiation markers CK14, CK low MW and smooth-muscle actin. Conclusions The developmentally regulated expression of integrin beta-1 in association with the establishment of a mature phenotype indicated by salivary gland tissue differentiation markers is suggestive of its role in salivary gland morphogenesis.

Congenital anomalies are the second highest cause of infant deaths, and, in most cases, diagnosis is a challenge. In this study, we characterize patterns of DNA copy number aberrations in different samples of post-mortem tissues from patients with congenital malformations. Twenty-eight patients undergoing autopsy were cytogenomically evaluated using several methods, specifically, Multiplex Ligation-dependent Probe Amplification (MLPA), microsatellite marker analysis with a MiniFiler kit, FISH, a cytogenomic array technique and bidirectional Sanger sequencing, which were performed on samples of different tissues (brain, heart, liver, skin and diaphragm) preserved in RNAlater, in formaldehyde or by paraffin-embedding. The results identified 13 patients with pathogenic copy number variations (CNVs). Of these, eight presented aneuploidies involving chromosomes 13, 18, 21, X and Y (two presented inter- and intra-tissue mosaicism). In addition, other abnormalities were found, including duplication of the TYMS gene (18p11.32); deletion of the CHL1 gene (3p26.3); deletion of the HIC1 gene (17p13.3); and deletion of the TOM1L2 gene (17p11.2). One patient had a pathogenic missense mutation of g.8535C>G (c.746C>G) in exon 7 of the FGFR3 gene consistent with Thanatophoric Dysplasia type I. Cytogenomic techniques were reliable for the analysis of autopsy material and allowed the identification of inter- and intra-tissue mosaicism and a better understanding of the pathogenesis of congenital malformations.

In the context of evidence-based clinical practice (EBCP), the reliability of empirical data is largely determined by the methodological quality of research design. PsycBITE™ (Psychological Database of Brain Impairment Treatment Efficacy) is a web-based database listing all published, empirical reports on the effectiveness of nonpharmacological interventions for the psychological consequences of acquired brain impairment (ABI). The aim of this study was to survey the listings of PsycBITE™ and examine the methodological quality of the reports it contains. Reports listed in PsycBITE™ include systematic reviews (SRs), randomised controlled trials (RCTs), non-RCTs, case series (CSs) and single-subject designs (SSDs). They are indexed according to research design, neurological group, patient age group, target area and intervention type. The PEDro Scale is used to rate the methodological quality of RCTs, nonRCTs and CSs, with maximum obtainable methodological quality rating (MQR) of 10/10, 8/10 and 2/10 respectively. A search identified 1298 reports indexed in PsycBITE™. The largest proportion was SSDs (39%), followed by CSs (22%), RCTs (21%), non-RCTs (11%) and SRs (7%). The majority of reports was concerned with stroke (41%), traumatic brain injury (29%) and Alzheimer's and related dementias (22%). The most frequently investigated deficits were communication/language/speech disorders (24%); independent/self-care activities (19%); behaviour problems (17%); memory impairments (17%); anxiety, depression, stress, adjustment (15%). Approximately half of the RCTs, non-RCTs and CSs were rated for methodological quality. Mean MQR scores for RCTs, non-RCTs and CSs were 4.49, 2.85 and 1.15 respectively. While some PEDro criteria were met by a high proportion of RCTs and non-RCTs (≥ 70%), other criteria were only met by a small proportion of reports (as low as 1.6%). There was no significant difference in MQR scores between RCTs focusing on different neurological groups or target areas. Furthermore, there was no discernible improvement in MQR score for RCTs published over the last three decades. The methodological quality of studies investigating the efficacy of rehabilitation interventions in ABI has been consistently modest over several decades. This is largely attributable to poor adherence to fundamental tenets of research design, and requires urgent remediation. RCTs (and to a lesser extent, non-RCTs) are research methodologies which can potentially yield a high level of evidence, but only if they are adequately designed. PsycBITE™ has the facility to raise awareness of these issues and be instrumental in promoting EBCP in the field of ABI.

Purpose The aim of this study was to compare pregnancy outcome and pathologic findings in cases of placental lake visualized on sonography in pregnancies without concurrent fetal or maternal disease. Methods Placental aspect was evaluated sonographically in 4,106 singleton pregnancies without maternal or fetal disease at between 15 and 34 weeks3 gestation. Fifty-nine cases presenting with placental lakes were followed through the end of pregnancy. Obstetric outcome was compared with that of cases with sonographically normal placental aspects (n = 37). Macroscopic and microscopic examinations for pathology were also performed in a few cases in both groups. Results Placental lakes were present in 2.2% (92/4,106) of the cases. No statistically significant difference was observed in birth weight, gestational age at delivery, adverse obstetric outcome, and macroscopic or microscopic results between the control and study groups. Conclusion Our findings do not seem to indicate an increase in the risk for an adverse pregnancy outcome in cases presenting with placental lakes. © 2005 Wiley Periodicals, Inc. J Clin Ultrasound 33:67–71, 2005