Metabolic profiling in children with autism spectrum disorder with and without mental regression: preliminary results from a cross-sectional case-control study.

INTRODUCTION: It is challenging to establish the mechanisms involved in the variety of well-defined clinical phenotypes in autism spectrum disorder (ASD) and the pathways involved in their pathogeneses. OBJECTIVES: The aim of the present study was to evaluate the metabolomic profiles of children with ASD subclassified by mental regression (AR) phenotype and with no regression (ANR). METHODS: The present study was a cross-sectional case-control study. Thirty children aged 2-6 years with ASD were included: 15 with ANR and 15 with AR. In addition, a control group of 30 normally developing children was selected and matched to the ASD group by sex and age. Plasma samples were analyzed with a metabolomics single platform methodology based on liquid chromatography-mass spectrometry. Univariate and multivariate analysis, including orthogonal partial least squares-discriminant analysis modeling and Shared-and-Unique-Structures plots, were performed using MetaboAnalyst 4.0 and SIMCA-P 15. The primary endpoint was the metabolic signature profiling among healthy children and autistic children and their subgroups. RESULTS: Metabolomic profiles of 30 healthy children, 15 ANR and 15 AR were compared. Several differences between healthy children and children with ASD were detected, involving mainly amino acid, lipid and nicotinamide metabolism. Furthermore, we report subtle differences between the ANR and AR groups. CONCLUSIONS: In this study, we report, for the first time, the plasmatic metabolomic profiles of children with ASD, including two different phenotypes based on mental regression status. The use of a liquid chromatography-mass spectrometry platform approach for metabolomics in ASD children using plasma appears to be very efficient and adds further support to previous findings in urine. Furthermore, the present study documents several changes related to amino acid, NAD+ and lipid metabolism that, in some cases, such as arginine and glutamate pathway alterations, seem to be associated with the AR phenotype. Further targeted analyses are needed in a larger cohort to validate the results presented herein.

Evaluation of the safety, tolerance and efficacy of 1-year consumption of infant formula supplemented with Lactobacillus fermentum CECT5716 Lc40 or Bifidobacterium breve CECT7263: a randomized controlled trial.

BACKGROUND: The microorganism present in breast milk, added to other factors, determine the colonization of infants. The objective of the present study is to evaluate the safety, tolerance and effects of the consumption of a milk formula during the first year of life that is supplemented with L. fermentum CECT5716 or Bifidobacterium breve CECT7263, two strains originally isolated from breast milk. METHODS: A randomized, double blind, controlled, parallel group study including healthy, formula-fed infants was conducted. Two hundred and thirty-six 1-month-old infants were selected and randomly divided into three study groups according to a randomization list. Infants in the control group received a standard powdered infant formula until 12 months of age. Infants in the probiotic groups received the same infant formula but supplemented with L. fermentum CECT5716 Lc40 or B. breve CECT7263. Main outcome was weigh-gain of infants as safety marker. RESULTS: One hundred and eighty-nine infants completed the eleven months of intervention (61 in control group, 65 in Lf group and 63 in Bb group). The growth of infants in the three groups was consistent with standards. No significant differences were observed in the main outcome, weight-gain (Control group: 5.77 Kg ± 0.95, Lf group: 5.77 Kg ± 1.31, Bb group: 5.58 Kg ± 1.10; p = 0.527). The three milk formulae were well tolerated, and no adverse effects were related to the consumption of any of the formula. Infants receiving B. breve CECT7263 had a 1.7 times lower risk of crying than the control group (OR = 0.569, CI 95% 0.568-0.571; p = 0.001). On the other hand, the incidence of diarrhoea in infants receiving the formula supplemented with L. fermentum CECT5716 was a 44% lower than in infants receiving the control formula (p = 0.014). The consumption of this Lactobacillus strain also reduced the duration of diarrhoea by 2.5 days versus control group (p = 0.044). CONCLUSIONS: The addition of L. fermentum CECT5716 Lc40 or B. breve CECT7263, two probiotic strains naturally found in breast milk, to infant formulae is safe and induces beneficial effects on the health of infants. TRIAL REGISTRATION: The trial was retrospectively registered in the US Library of Medicine ( www.clinicaltrial.gov ) with the number NCT03204630 . Registered 11 August 2016.

The impact of mastectomy type on the Female Sexual Function Index (FSFI), satisfaction with appearance, and the reconstructed breast's role in intimacy.

BACKGROUND: As mastectomy rates increase and overall survival for early breast cancer improves, a better understanding of the long-term consequences of mastectomy is needed. We sought to explore the correlation of specific mastectomy type with the Female Sexual Function Index (FSFI), body image satisfaction, and the reconstructed breast's role in intimacy. METHODS: This study is a secondary analysis of a cross-sectional survey including a retrospective chart review. Patients at least one year from primary surgery were invited to complete the survey between 2012 and 2014. Baseline characteristics and survey responses were compared between three mastectomy groups: total/modified radical (TMRM), skin-sparing (SSM), and nipple-sparing (NSM). All patients underwent reconstruction. RESULTS: Of 453 invited, 268 (59%) completed the survey. Sixty underwent mastectomy with reconstruction: 16 (27%) TMRM, 36 (60%) SSM, and 8 (13%) NSM. There were no significant differences in median total FSFI scores between groups, yet median FSFI scores for the NSM group indicated sexual dysfunction. After adjusting for receipt of chemotherapy and/or radiation, NSM had the lowest median desire score. There was a trend for the NSM group to be the least satisfied with postoperative appearance, but also more likely to report that the chest was "often" caressed during intimacy. However, nearly 40% of the NSM group reported that caress of the reconstructed breast was unpleasant. CONCLUSION: NSM offers patients the greatest opportunity for preservation of their native skin envelope and potentially enhanced cosmetic outcome, but our results did not demonstrate superior sexual function or body image outcomes in this group. By highlighting surgical consequences of mastectomy preoperatively, surgeons may better set realistic patient expectations regarding both aesthetic and functional outcomes after breast cancer surgery. With clearer expectations, patients will have a better opportunity for improved surgical decision-making.

Long-term safety of early consumption of Lactobacillus fermentum CECT5716: A 3-year follow-up of a randomized controlled trial.

Lactobacillus fermentum CECT5716 is a probiotic strain originally isolated from human breast milk. Previous clinical studies in infants showed that the early administration of a milk formula containing this probiotic strain was safe and may be useful for the prevention of community-acquired infections. This is a 3-year follow-up study aimed at evaluating the long-term effects produced by the early consumption of an infant formula supplemented with L. fermentum CECT5716 (experimental group, EG) compared with a control formula without the probiotic (control group, CG). The infants included in this follow-up study had previously completed a 5-month randomized double-blind controlled trial (from 1 to 6 months of age), where the safety and tolerance of the probiotic formula was evaluated. The main outcome of the follow-up study was the growth of the children. The secondary outcomes included the incidence of infectious and non-infectious diseases, parameters related with intestinal function and faecal microbiota. At 3 years, the mean values of weight, length and head circumference were similar in children of the EG compared with those of the CG. No differences were observed in the incidence of infectious and non-infectious diseases or disorders related with intestinal function. The pattern of faecal microbiota was also similar between both groups. In conclusion, this 3-year study shows that the early administration of the probiotic of L. fermentum CECT5716 in an infant formula is safe and it does not produce measurable differences in children compared with a control formula.

Genomic landscape and immune-related gene expression profiling of epithelial ovarian cancer after neoadjuvant chemotherapy.

Platinum-based neoadjuvant chemotherapy followed by interval debulking surgery is an accepted treatment for patients with stage III or IV epithelial ovarian cancer who are not suitable for primary debulking surgery. The identification of suitable adjuvant treatments in these patients is an unmet need. Here, we explore potential genomic characteristics (mutational and immune-associated expression profiles) in a series of patients undergoing neoadjuvant chemotherapy. Tumor samples from biopsy and interval debulking surgery were analyzed for mutational landscape and immune profiling, together with detailed immunohistochemistry using different immune cell markers, and correlated with clinicopathological characteristics and potential response to neoadjuvant chemotherapy. No major differences in the mutational landscape were observed in paired biopsy and surgery samples. Genomic loss of heterozygosity was found to be higher in patients with total/near-total tumor response. The immune gene expression profile after neoadjuvant chemotherapy revealed activation of several immune regulation-related pathways in patients with no/minimal or partial response. In parallel, neoadjuvant therapy caused a significant increase of tumor-infiltrating lymphocyte population abundance, primarily due to an augmentation of the CD8+ T cell population. Remarkably, these changes occurred irrespective of potential homologous recombination defects, such as those associated with BRCA1/2 mutations. Our study strengthens the use of loss of heterozygosity as a biomarker of homologous repair deficiency. The changes of immune states during neoadjuvant chemotherapy reveal the dynamic nature of tumor-host immune interactions and suggest the potential use of immune checkpoint inhibitors or their combination with poly-ADP polymerase inhibitors in high stage and grade epithelial ovarian cancer patients undergoing neoadjuvant therapy.

Male DCIS diagnosed after use of over-the-counter hormonal supplement.

INTRODUCTION: Male breast cancer is a rare disease. Although epidemiologic and genetic factors are associated with male breast cancer, hormonal factors may also play a role. CASE PRESENTATION: We report the case of a 39-year-old BRCA negative male patient taking a sexual performance enhancement supplement who presented with worsening asymmetric gynecomastia and unilateral spontaneous bloody nipple discharge and was found to have ductal carcinoma in-situ. DISCUSSION: The altered cellular environment related to the hormone contents of the supplement coincided with the rapid worsening of his gynecomastia and may have played a role in the development of the ductal carcinoma in-situ, or growth of an existing focus. CONCLUSION: The use of hormonal male enhancement supplements can lead to higher levels of androgens in users. It is possible for this altered hormonal environment to cause the growth of tumor or promote the progression of an existing focus.

Body mass index (BMI), postoperative appearance satisfaction, and sexual function in breast cancer survivorship.

PURPOSE: We sought to explore the correlation between BMI and postoperative sexual function, body image, and breast-specific sensuality before and after breast cancer surgery. METHODS: A cross-sectional survey of patients at least 1 year from surgery employed the Female Sexual Function Index (FSFI) and investigator-generated questions. Patients who underwent lumpectomy (L), mastectomy (M), and mastectomy with reconstruction (MR) were compared across three BMI groups: normal weight, overweight, and obese. RESULTS: Two hundred fifty-five patients underwent lumpectomy (L, n = 174), mastectomy (M, n = 22), or mastectomy with reconstruction (MR, n = 59). Median age was 57 (range 30-93) and median BMI was 28 (range 19-45). Obese and overweight women reported more appearance dissatisfaction (18.1 and 13.0%) than normal weight women (4.1%) (p = 0.01). Lower satisfaction was associated with increasing BMI within the MR group (p = 0.05). The obese group's median FSFI score met criteria for sexual dysfunction (25.90, range 11.30-33.10). More overweight women reported their chest played an important role in intimacy before and after surgery, but a postoperative decline in the importance of this role was observed in all groups. CONCLUSIONS: Greater post-treatment BMI is inversely related to postoperative appearance satisfaction, particularly in those undergoing mastectomy with reconstruction. The role of the breast in intimacy is greatest in overweight women, but decreases postoperatively in all BMI groups. IMPLICATIONS FOR CANCER SURVIVORS: Postoperative appearance satisfaction and sexual function seems to be correlated to post-treatment BMI, which highlights the need to encourage perioperative weight management for improved survivorship outcomes.

Variability in a family with an insertion involving 5p.

Cri-du-chat syndrome is due to a partial deletion of the short arm of chromosome 5 and comprises a catlike cry, minor facial anomalies, growth delays, and psychomotor retardation. We identified a family with an insertion involving chromosome areas 5p and 16q. Four relatives are balanced carriers and have a normal phenotype, 5 have inherited the insertion in an unbalanced form with 2 resulting in partial trisomy of 5p and 3 in partial monosomy of 5p. The 3 individuals show a variable phenotype with respect to mental delay and some of the findings of cri-du-chat syndrome. The extent of the 5p deletion in this family was determined using previously mapped markers. The deletion in this family was informative for further refining the phenotypic map for the cri-du-chat syndrome. This family demonstrates the importance of performing phenotype-genotype correlation studies based on the presence rather than the absence of abnormalities.

Optimization of computed tomography technique to demonstrate the fine structure of the lung.

The purpose of this investigation was to optimize the reconstruction algorithm and the slice thickness of computed tomography (CT) for the study of the fine structure of the lung. In 75 patients, we performed routine thoracic CT examination and obtained two high-resolution CT (HRCT) slices at the same level using the standard and bone algorithms, or using the slice thickness of 1.5 mm and 3.0 mm. Side-by-side comparison of the standard and bone images revealed that more branching of the small vessels and more small bronchi could be recognized on the bone image than on the standard image. Thickened bronchovascular bundles and interlobular septa were demonstrated more clearly on the bone image than on the standard image. There was no significant difference in the CT attenuation value between the standard and bone images. The difference between 1.5 mm and 3.0 mm images when demonstrating the small vessels and bronchi was minimal in such lesions as lymphangitis carcinomatosa and radiation fibrosis. Thus HRCT, with a slice thickness of 1.5 mm and 3.0 mm reconstructed by the bone algorithm, is suitable for the demonstration of the fine structure of the lung.

Sequential morphologic changes of elastase-induced pulmonary emphysema in pig lungs. Evaluation by high-resolution computed tomography.

The authors evaluated the early morphologic changes of elastase-induced pulmonary emphysema in the pig and correlated the findings with high-resolution computed tomography (HRCT). Nine Yorkshire pigs were included in this investigation; in seven, pulmonary emphysema was induced by 2 mg/kg body weight of elastase instilled selectively into the left lower lobe bronchus. Animals were studied by CT at 0, 1, 2, 3, 7, 14, and 21 days. At the completion of the experiment, the lungs were removed, inflated, fixed and dried, and subsequently sliced corresponding to the CT sections. The gross appearance, histologic appearance, and HRCT were correlated. On HRCT, sequential changes from early edema to development of emphysema were noted. Panlobular, centrilobular and paraseptal emphysema were observed. Elastase-induced pulmonary emphysema in the pig is a useful and reproducible animal model, and high-resolution computed tomography depicts the morphologic changes observed both by gross pathologic observations and histologic observations.

Pulmonary scintigraphy in elastase-induced emphysema in pigs. Correlation with high-resolution computed tomography and histology.

OBJECTIVES: The objective of this study is to evaluate the mild physiologic changes of elastase-induced pulmonary emphysema in the pig by radionuclide scintigraphy and to correlate these findings with high-resolution computed tomography (HRCT) and histologic examination. METHODS: Eight 7- to 12-week-old Yorkshire pigs were studied. Perfusion and ventilation studies were performed in six pigs at 1- or 2-week intervals after elastase instillation. HRCT was simultaneously performed for correlation with radionuclide scintigraphy. For the perfusion scans, technetium 99m (99mTc) macroaggregated albumin (MAA) was used, and both planar and single-photon emission CT (SPECT) images were obtained. Ventilation studies were performed with xenon-133 gas with dynamic sequential imaging. RESULTS: Histopathologic findings demonstrated dilatation and destruction of the alveoli and were similar to those previously reported by the authors. The SPECT perfusion images showed significantly impaired perfusion of the involved segment of the lung, corresponding to the region where elastase was instilled. The planar xenon-133 ventilation scintigraphy did not show abnormal air trapping. The mild emphysema induced with elastase manifested as decreased and impaired perfusion with no detectable ventilation abnormalities. The sensitivity of SPECT perfusion studies for the detection of the mild changes of elastase-induced pulmonary emphysema were higher than that of HRCT. CONCLUSIONS: The perfusion studies reflect functional or physiologic changes in contrast to structural changes seen on HRCT. This pig model was valuable to study the scintigraphic manifestation of elastase-induced pulmonary emphysema.

Affective disorder associated with a balanced translocation involving chromosome 14 and 18.

We report a case of a women with psychiatric illness that includes bipolar disorder who has a karyotype of 46,XX,t(14;18)(q11.2;q22.1). The region on chromosome 18 that is involved in the translocation has been implicated in other families through linkage and association studies as possibly containing a gene for bipolar illness.

Computed tomography of normal and calcified coronary arteries.

The association between coronary artery calcification (CAC) and coronary artery disease is well established. The objectives of this article are to define the cross-sectional anatomy of the coronary arteries and to demonstrate the prevalence of CAC as seen on routine computed tomography (CT) of the thorax. A CT scan of a cadaver heart was performed in normal anatomic position. Additionally, a retrospective analysis of 103 consecutive thoracic scans was done by three experienced radiologists. The cross-sectional anatomy of the coronary arteries is described based on both these studies, and the prevalence of coronary calcification from the retrospective review was determined. The left anterior descending was the most commonly calcified artery (43% of all patients) followed in order by the left coronary (37%), circumflex (33%), and right coronary (20%). Seventy-nine percent of patients older than age 65 demonstrated coronary calcification on CT. This prevalence approaches that of reported autopsy series. Knowledge and understanding of the cross-sectional anatomy of coronary arteries is essential for detection of coronary artery calcification. We recommend that the presence of CAC should be reported on all thoracic CT scans because coronary calcification may signal unsuspected coronary artery disease.

Investigation on the effect of sharp phantom edges on point dose measurement during patient-specific dosimetry with Rapid Arc.

The objective of this work was to investigate and quantify the effect of sharp edges of the phantom on the point dose measurement during patient-specific dosimetry with Rapid Arc (RA). Ten patients with carcinoma of prostate were randomly selected for this dosimetric study. Rapid Arc plans were generated with 6 MV X-rays in the Eclipse (v 8.6.14) with single arc (clockwise). Dosimetry verification plans were generated for two phantoms (cylindrical and rectangular). The cylindrical phantom was solid water (diameter 34 cm) and the rectangular phantom was a water phantom (25 cm × 25 cm × 10 cm). These phantoms were pre-scanned in computed tomography (CT) machine with cylindrical ionization chamber (FC65) in place. The plans were delivered with Novalis Tx linear accelerator with 6 MV X-rays for both the phantoms separately. The measured dose was compared with the planned dose for both the phantoms. Mean percentage deviation between measured and planned doses was found to be 4.19 (SD 0.82) and 3.63 (SD 0.89) for cylindrical and rectangular phantoms, respectively. No significant dosimetric variation was found due to the geometry (sharp edges) of the phantom. The sharp edges of the phantom do not perturb the patient specific Rapid Arc dosimetry significantly.

Factors associated with depression in patients with Parkinson's disease A multicenter study in Lima, Peru / Factores asociados a la depresión en pacientes con enfermedad de Parkinson Un estudio multicéntrico en Lima, Perú

Introduction: The diagnosis and treatment of depression in patients with Parkinson's disease (PD) is inadequate, often contributing to a reduced quality of life, rapid disease progression, higher cognitive impairment, and an increased burden of care for family members of patients with PD. Objective: To determine the factors associated with depression in PD and to examine the frequency of depressive symptoms among patients with PD. Methods: This study was an observational, analytical, multicenter study of a cross-sectional cohort, conducted between July 2016 and May 2017. PD patients were recruited from neurology clinics in Lima, Peru. All statistical analyses were performed using descriptive statistics. Bivariate and multivariate logistic regression analyses were calculated using STATA. Results: Out of 124 patients (average age: 68.7 years; 58% males) included in the study 60.5% (75/124) presented with symptoms of depression; only 20% (25/124) received antidepressants. Factors associated with depression in PD included: unemployment, falls, freezing of gait, involuntary movements micrographia, stooped posture, hyposmia, movement disorders in sleep, rapid disease progression, and the use of MAOIs. Furthermore, statistically significant differences were found in disease duration, UPDRS and MMSE scores, Hoehn and Yahr (HY) stage, and length of time taking L-dopa between PD patients with and without depressive symptoms. Conclusion: Factors associated with depressive symptoms in patients with PD were hyposmia, rapid progression of the disease, the use of L-dopa, and use of MAOIs. The frequency of depressive symptoms in patients with PD is high; early diagnosis and prompt treatment are needed to improve their quality of life and the family environment.

Introducción: El diagnóstico y el tratamiento de la depresión en pacientes con enfermedad de Parkinson (EP) son inadecuados, lo que a menudo contribuye a una menor calidad de vida, una rápida progresión de la enfermedad, un mayor deterioro cognitivo y una mayor carga de cuidados para los familiares de los pacientes con EP. Objetivo: Determinar los factores asociados con la depresión en la EP y examinar la frecuencia de los síntomas depresivos entre los pacientes con EP. Métodos: Este estudio fue un estudio observacional, analítico y multicéntrico de una cohorte transversal, realizado entre julio de 2016 y mayo de 2017. Los pacientes con EP fueron reclutados en clínicas de neurología en Lima, Perú. Todos los análisis estadísticos se realizaron utilizando estadísticas descriptivas. Los análisis de regresión logística bivariada y multivariada se calcularon utilizando STATA. Resultados: De 124 pacientes (edad media: 68,7 años; 58% varones) incluidos en el estudio, el 60,5% (75/124) presentó síntomas de depresión; sólo el 20% (25/124) recibió antidepresivos. Los factores asociados a la depresión en la EP incluyeron: desempleo, caídas, congelamiento de la marcha, micrografía de movimientos involuntarios, postura encorvada, hiposmia, trastornos del movimiento durante el sueño, progresión rápida de la enfermedad y el uso de IMAO. Además, se encontraron diferencias estadísticamente significativas en la duración de la enfermedad, puntuaciones UPDRS y MMSE, estadio de Hoehn y Yahr (HY) y tiempo de toma de L-dopa entre pacientes con EP con y sin síntomas depresivos. Conclusión: Los factores asociados a los síntomas depresivos en pacientes con EP fueron la hiposmia, la progresión rápida de la enfermedad, el uso de L-dopa y el uso de IMAO. La frecuencia de síntomas depresivos en pacientes con EP es alta, por lo que se requiere un diagnóstico temprano y un tratamiento oportuno para mejorar su calidad de vida y el entorno familiar.

Clinical and molecular evaluation of four patients with partial duplications of the long arm of chromosome 18.

Four individuals with partial duplications of the long arm of chromosome 18 were analyzed at the clinical, cytogenetic, and molecular levels. Two of the individuals had duplications of the long arm from 18q21.1-qter because of inheritance of an unbalanced translocation. Both of these individuals displayed the clinical phenotype characteristic of Edwards syndrome. Two other patients had de novo interstitial duplications of 18q but did not have a clinical diagnosis of Edwards syndrome. The extent of the duplicated material in each patient was determined initially by using cytogenetic analysis and subsequently with more detailed comparisons of the duplicated regions by using molecular probes derived from a chromosome 18-specific lambda phage library. The results demonstrated that one of the de novo interstitial duplications that did not result in the Edwards syndrome phenotype had a more proximal breakpoint than that of the partial duplications of the two patients with features of Edwards syndrome. These results suggest that a single critical region for Edwards syndrome in the proximal portion of 18q is unlikely.

STS map of genes and anonymous DNA fragments on human chromosome 18 using a panel of somatic cell hybrids.

Somatic cell hybrids containing different deleted regions of chromosome 18 derived from patients with balanced translocations or terminal deletions were used to create a deletion mapping panel. Twenty-four sequence-tagged sites (STSs) for 17 genes and 7 anonymous polymorphic DNA fragments were identified. These STSs were used to map the 24 loci to 18 defined regions of chromosome 18. Both ERV1, previously mapped to 18q22-q23, and YES1, previously mapped to 18q21.3, were found to map to 18q11.21-pter. Several genes previously mapped to 18q21 were found to be in the order cen-SSAV1-DCC-FECH-GRP-BCL2-PLANH2-tel. The precise mapping of genes to chromosome 18 should help in determining whether these genes may be involved in the etiology of specific chromosomal syndromes associated with chromosome 18. The mapping of the polymorphic loci will assist in the integration of the physical map with the recombination map of chromosome 18.

Solitary pulmonary nodules: comparison of classification with standard, thin-section, and reference phantom CT.

Standard, thin-section, and reference phantom computed tomography (CT) were performed to evaluate 75 consecutive patients with solitary pulmonary nodules. Follow-up was available for 62 nodules in 59 patients; 53 of the nodules were benign and nine were malignant. Twenty-one of the 62 nodules were assessed as benign with thin-section CT, while 33 of the 62 nodules were assessed as benign with reference phantom CT. Two of the nodules classified as benign with both thin-section and reference phantom CT proved to be malignant (a peripheral, ossified carcinoid and a 3.5-cm-diameter calcified carcinoma). The sensitivity of reference phantom CT (58%) for classification of benign nodules was higher than the sensitivity of thin-section CT (36%). The sensitivity of standard CT was lowest (12%). The presence of fat at thin-section CT was a reliable criterion for benignancy in six hamartomas. While both thin-section and reference phantom CT were useful in the identification of benign pulmonary nodules, reference phantom CT increased sensitivity by 22% compared with thin-section CT.