Effect of Vitamin D and Docosahexaenoic Acid Co-Supplementation on Vitamin D Status,Body Composition,and Metabolic Markers in Obese Children: A Randomized,Double Blind,Controlled Study

Obese children are at high risk of developing vitamin D deficiency. Omega-3 polyunsaturated fatty acids and their derivatives might have a beneficial effect on vitamin D status of obese children, due to their anti-inflammatory action, and increasing its absorption. This multicenter, randomized, double-blind controlled study aims to investigate the effect of vitamin D and docosahexaenoic acid (DHA) co-supplementation for six months on vitamin D status, body composition, and metabolic markers of obese children with vitamin D deficiency. A total of 108 children were enrolled and 73 children completed the study: 33 were supplemented with an oral dose of 500 mg of DHA and 1200 IU/day of vitamin D3 and 41 were supplemented with 1200 IU/day of vitamin D3 + wheat germ oil. At the end of the study, more than 50% of the subjects improved their vitamin D status. However, co-supplementation was not more effective than vitamin D plus wheat germ oil. Fat mass percentage was significantly reduced, and body mass index improved in both groups, even if all the subjects were still obese at the end of the study. Children receiving both vitamin D and DHA presented a higher increase of DHA levels that could be relevant to prevent inflammatory-associated complications of obesity, but they had no effect on vitamin D levels.     

Relapse in medulloblastoma: what can be done after abandoning high-dose chemotherapy? A mono-institutional experience

Purpose

We retrospectively report strategies used for medulloblastoma patients progressing after craniospinal irradiation where we aimed for: symptom control, a satisfactory quality of life, accrual in phase 1–2 trials, when available, and the first two conditions could no longer be satisfied by already experienced second-line strategies.

Methods

Surgery was used in cases of doubtful relapse or when only one site was affected. Radiotherapy was given whenever possible, especially to relieve symptoms. The main chemotherapy regimens were oral temozolomide/etoposide, intravenous (iv.) cisplatin/etoposide, iv. gemcitabine/oxaliplatin, an oral sonic hedgehog pathway inhibitor and oral melphalan.

Results

Between 1998 and 2011, we treated 18 patients relapsed after median 20 months. Nine had relapsed locally, four had dissemination, three single metastases, and two had one synchronous local and metastatic recurrence. Responses to chemotherapy were seen in 32 % of cases. The median hospital stay for treatments/complications was 19 days. The 1- and 3-year progression-free survival (PFS) rates were 28?±?10 % and 0 %, respectively, for OS, they were 44?±?12 % and 22?±?10 % but no patient was cured. The median PFS after a first relapse was 7 months (range 1–29); the median OS was 7 months (range 4–44). No patients died due to treatment toxicity. Late recurrence (more than 1–2 years after diagnosis) and involvement of single sites were favorable prognostic factors.

Conclusions

Without succeeding in patients cure, we ensured them further treatment with short hospital stay thus affording low personal and social costs. The chances of cure may emerge from tailored therapies according to genetic stratification.     

Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism

The Autism Genome Project has assembled two large datasets originally designed for linkage analysis and genome-wide association analysis, respectively: 1,069 multiplex families genotyped on the Affymetrix 10 K platform, and 1,129 autism trios genotyped on the Illumina 1 M platform. We set out to exploit this unique pair of resources by analyzing the combined data with a novel statistical method, based on the PPL statistical framework, simultaneously searching for linkage and association to loci involved in autism spectrum disorders (ASD). Our analysis also allowed for potential differences in genetic architecture for ASD in the presence or absence of lower IQ, an important clinical indicator of ASD subtypes. We found strong evidence of multiple linked loci; however, association evidence implicating specific genes was low even under the linkage peaks. Distinct loci were found in the lower IQ families, and these families showed stronger and more numerous linkage peaks, while the normal IQ group yielded the strongest association evidence. It appears that presence/absence of lower IQ (LIQ) demarcates more genetically homogeneous subgroups of ASD patients, with not just different sets of loci acting in the two groups, but possibly distinct genetic architecture between them, such that the LIQ group involves more major gene effects (amenable to linkage mapping), while the normal IQ group potentially involves more common alleles with lower penetrances. The possibility of distinct genetic architecture across subtypes of ASD has implications for further research and perhaps for research approaches to other complex disorders as well.     

Effects of reinforcement,proximity, and orientation on verbal behavior of female schizophrenics

Evaluated effects of reinforcement, proximity, and orientation on verbal behavior of female schizophrenics. Sixty-four inpatient state hospital volunteers (36 schizophrenics and 33 hospitalized controls) either were reinforced verbally or nonreinforced for construction of appropriate sentences. Also, participants were exposed to near or far proximity as well as direct or indirect orientation. Results indicated that schizophrenics performed best in the indirect orientation condition. While no differential group effects were seen across diagnosis, participants on the average responded more effectively when reinforced. These findings are contradictory to those reported in earlier studies of verbal conditioning in schizophrenics. Discussed were the detrimental effects of attentional demands on verbal conditioning in schizophrenics and the effectiveness of verbal reinforcement across hospitalized patients.     

Aberrant expression of CD7 in myeloblasts is highly associated with de novo acute myeloid leukemias with FLT3/ITD mutation

Acute myeloid leukemia (AML) with normal cytogenetics represents approximately 40% to 50% of de novo AML. This heterogeneous AML subgroup constitutes the single largest cytogenetic group with an intermediate prognosis. Previous studies have suggested that the Fms-like tyrosine kinase-3 internal tandem duplication (FLT3/ITD) mutation-positive de novo AML may represent a distinctive subgroup of AML. We analyzed the clinical and pathologic features of 15 cases of de novo AML with normal cytogenetics and with the FLT3/ITD mutation. In comparison with patients with AML without the FLT3/ITD mutation, patients with FLT3/ITD+ AML are relatively younger, more often have marked peripheral leukocytosis with a higher number of circulating blasts at initial examination, more often have minimal differentiation morphologic features, more frequently have abnormal CD7 coexpression, and have poorer outcome. Close association of aberrant CD7 expression and FLT3/ITD mutation in the myeloblasts of FLT3/ITD+ AML suggests that FLT3/ITD- mediated leukemic transformation occurs in the more early stage of myeloid progenitor cells.     

Triage of ovarian masses

Background: Triage of ovarian masses for appropriate management is important in ensuring the best outcome for patients. The Risk of Malignancy Indices (RMI) seem to represent a low cost and effective tool for triage and management of women with ovarian masses.
Aim: To review patients with an ovarian mass referred to the Gynaecological Cancer Centre at the Royal Hospital for Women, and to assess the effectiveness of the RMI in differentiating benign from malignant tumours in this group of patients.
Methods: A retrospective review of the case records of all patients with an ovarian mass referred to our centre from January 2003 to December 2005 was undertaken.
Results: Two hundred and four patients were eligible for RMI calculation. An RMI of < 200 correctly identified 83 of 108 (77%) benign ovarian tumours. An RMI of > 200 correctly identified 11 of 19 (58%) borderline ovarian tumours and 70 of 77 (91%) invasive ovarian tumours. An RMI of > 200 had a sensitivity of 84%, specificity of 77%, positive predictive value of 76% and negative predictive value of 85% in detecting both borderline and invasive ovarian tumours. The false negative rate for invasive tumours was 9%.
Conclusions: This study showed that using RMI at a cut-off of 200 for referral could have prevented 83 benign cases (41%) from being referred. We propose that the RMI could be utilised as a triage tool for referral of ovarian masses to gynaecological cancer centres.     

A Community Study of SARS-CoV-2 Detection by RT-PCR in Saliva: A Reliable and Effective Method

Efficient, wide-scale testing for SARS-CoV-2 is crucial for monitoring the incidence of the infection in the community. The gold standard for COVID-19 diagnosis is the molecular analysis of epithelial secretions from the upper respiratory system captured by nasopharyngeal (NP) or oropharyngeal swabs. Given the ease of collection, saliva has been proposed as a possible substitute to support testing at the population level. Here, we used a novel saliva collection device designed to favour the safe and correct acquisition of the sample, as well as the processivity of the downstream molecular analysis. We tested 1003 nasopharyngeal swabs and paired saliva samples self-collected by individuals recruited at a public drive-through testing facility. An overall moderate concordance (68%) between the two tests was found, with evidence that neither system can diagnose the infection in 100% of the cases. While the two methods performed equally well in symptomatic individuals, their discordance was mainly restricted to samples from convalescent subjects. The saliva test was at least as effective as NP swabs in asymptomatic individuals recruited for contact tracing. Our study describes a testing strategy of self-collected saliva samples, which is reliable for wide-scale COVID-19 screening in the community and is particularly effective for contact tracing.     

Transplanted skin-derived precursor stem cells generate enteric ganglion-like structures in vivo

Introduction

Hirschsprung’s disease is characterized by a developmental arrest of neural crest cell migration, causing distal aganglionosis. Transplanted cells derived from the neural crest may regenerate enteric ganglia in this condition. We investigated the potential of skin-derived precursor cells (SKPs) to engraft and to differentiate into enteric ganglia in aganglionic rat intestine in vivo.

Methods

Adult Lewis rat jejunal segments were separated from intestinal continuity and treated with benzalkonium chloride to induce aganglionosis. Ganglia were identified via immunohistochemical stains for S100 and β-III tubulin (TUJ1). SKPs were procured from neonatal Lewis rats expressing enhanced green fluorescent protein (GFP) and cultured in neuroglial-selective media. SKP cell line expansion was quantified, and immunophenotypes were assessed by immunocytochemistry. Aganglionic segments underwent SKP transplantation 21–79 days after benzalkonium chloride treatment. The presence of GFP + cells, mature neurons, and mature glia was evaluated at posttransplant days 1, 6, and 9.

Results

Benzalkonium chloride-induced aganglionosis persisted for at least 85 days. Prior to differentiation, SKPs expressed S100, denoting neural crest lineage, and nestin, a marker of neuronal precursors. Differentiated SKPs in vitro expressed GFAP, a marker of glial differentiation, as well as TUJ1 and several enteric neurotransmitters. After transplantation, GFP + structures resembling ganglia were identified between longitudinal and circular smooth muscle layers.

Conclusion

SKPs are capable of engraftment, migration, and differentiation within aganglionic rodent intestine in vivo. Differentiated SKPs generate structures that resemble enteric ganglia. Our observations suggest that SKPs represent a potential gangliogenic therapeutic agent for Hirschsprung’s disease.     

Robotic distal pancreatectomy and nephrectomy for living donor pancreas-kidney transplantation

Living organ donation is of increasing importance to satisfy the demand of good quality organs for patients remaining for extended periods on the waiting list. While the benefit for the recipient is undeniable, the organ procurement represents an important burden to live donors in terms of invasiveness and long-term consequences. The latter can be minimized with careful donor selection. With the avenue of minimally invasive surgery, and more recently the availability of robotic technology, the surgical trauma can be reduced, the safety increased, and the recovery accelerated. In this case report, we present the first reported combined robotic distal pancreatectomy and left nephrectomy from a live donor. The surgery was performed using the Da Vinci robotic system with four small trocar incisions, and a short infraumbilical midline incision for hand-assistance and extraction of the organ. The donor operation lasted 5 hr and blood loss was only 100 mL. Both donor and recipient had an uncomplicated postoperative course and present with normal endocrine and renal function 3 mo after surgery. In experienced hands, advanced surgical procedures such as combined distal pancreatectomy and left nephrectomy can be safely performed in living donors with minimally invasive robotic surgery, dramatically reduced surgical trauma, and impressive postoperative recovery. The availability of minimally invasive robotic surgery may further increase the willingness for live organ donation from suitable donors.