Predictors of ovarian malignancy in children: Overcoming clinical barriers of ovarian preservation

Background/Purpose

Ovarian preservation is desirable in girls with benign ovarian masses. We aimed to 1) identify clinical predictors of malignant ovarian masses, 2) investigate how often ovarian tissue is present to preserve in benign masses, and 3) identify factors associated with successful ovarian preservation.

Methods

Retrospective analysis (1997–2012) of girls age 1–18 years with an ovarian mass managed operatively. Data on presenting symptoms, imaging, biochemical markers, treatment, outcome, and pathology were extracted.

Results

We identified 150 patients. Large mass size, solid components, and elevated tumor markers (AFP, βHCG, and/or LDH) were significantly predictive of malignancy. All masses < 10 cm, predominantly cystic, and with negative tumor markers were benign. Masses with all three of these characteristics would decrease a 20% malignancy pretest probability to a posttest probability of 0.25%. Benign masses managed by oophorectomy contained normal ovarian tissue in 76% of the specimens. For benign masses, successful ovarian preservation was significantly associated with size < 10 cm, predominantly cystic, laparoscopy, and absence of torsion or calcifications.

Conclusion

Ovarian masses that are < 10 cm, primarily cystic, and have negative tumor markers are most likely benign. Viable ovarian tissue is frequently present in benign masses, so significant efforts should be made for ovarian preservation.     

PEG shielded polymeric double-layered micelles for gene delivery.

A combination of A-B and B-C block copolymers was used to encapsulate DNA inside pEG coated particles, where A is a cationic block (poly(dimethylaminoethyl methacrylate), pDMAEMA) for DNA binding and condensation, B is a hydrophobic block (poly(butylmethacrylate), pBMA) and C is a polyethylene glycol (pEG) block. The AB and BC block copolymers were synthesized by transition metal mediated radical polymerization. The AB block copolymer had a fixed pBMA molecular weight of 3800 g/mol and a varying pDMAEMA molecular weight (from 22 to 65 kg/mol), the BC block copolymer had a fixed composition (pBMA 9000 g/mol; pEG 2000 g/mol). Plasmid DNA containing particles were made via a detergent dialysis method. By this method, particles of approximately 120 nm, as determined by dynamic light scattering (DLS), with a near neutral charge were formed, independent of the DMAEMA block size. DLS measurements and gel electrophoresis indicated that the particles were very stable in cell culture medium at 37 degrees C and resistant to anionic exchange by poly-l-aspartic acid. The particles were able to transfect COS-7 and OVCAR-3 cells with minor toxicity if incubated for 1 or 4 h; incubation for 24 h resulted in an increased toxicity. This paper shows that small polyplexes with near neutral charge can be obtained via a convenient detergent dialysis method using pDMAEMA-b-pBMA and pBMA-b-pEG. These particles may be interesting for in vivo experiments where particles with high positive charges have adverse interactions with blood components.     

Fetal alcohol spectrum disorders

Prenatal alcohol exposure (PAE) is one of the most prevalent and modifiable risk factors for somatic, behavioral, and neurological abnormalities. Affected individuals exhibit a wide range of such features referred to as fetal alcohol spectrum disorders (FASD). These are characterized by a more or less specific pattern of minor facial dysmorphic features, growth deficiency and central nervous system symptoms. Nevertheless, whereas the diagnosis of the full-blown fetal alcohol syndrome does not pose a major challenge, only a tentative diagnosis of FASD can be reached if only mild features are present and/or maternal alcohol consumption during pregnancy cannot be verified. The respective disorders have lifelong implications. The teratogenic mechanisms induced by PAE can lead to various additional somatic findings and structural abnormalities of cerebrum and cerebellum. At the functional level, cognition, motor coordination, attention, language development, executive functions, memory, social perception and emotion processing are impaired to a variable extent. The long-term development is characterized by disruption and failure in many domains; an age-adequate independency is frequently not achieved. In addition to primary prevention, individual therapeutic interventions and tertiary prevention are warranted; provision of extensive education to affected subjects and their caregivers is crucial. Protective environments are often required to prevent negative consequences such as delinquency, indebtedness or experience of physical/sexual abuse.     

Medial prefrontal theta phase coupling during spatial memory retrieval

Memory retrieval is believed to involve a disparate network of areas, including medial prefrontal and medial temporal cortices, but the mechanisms underlying their coordination remain elusive. One suggestion is that oscillatory coherence mediates inter‐regional communication, implicating theta phase and theta‐gamma phase‐amplitude coupling in mnemonic function across species. To examine this hypothesis, we used non‐invasive whole‐head magnetoencephalography (MEG) as participants retrieved the location of objects encountered within a virtual environment. We demonstrate that, when participants are cued with the image of an object whose location they must subsequently navigate to, there is a significant increase in 4–8 Hz theta power in medial prefrontal cortex (mPFC), and the phase of this oscillation is coupled both with ongoing theta phase in the medial temporal lobe (MTL) and perceptually induced 65–85 Hz gamma amplitude in medial parietal cortex. These results suggest that theta phase coupling between mPFC and MTL and theta‐gamma phase‐amplitude coupling between mPFC and neocortical regions may play a role in human spatial memory retrieval. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.     

Bildgebung bei epileptischen Enzephalopathien

Epileptic encephalopathies (EE) belong to the group of epilepsies which are associated with expressed cognitive and behavioral disturbances subsequent to epileptic activity. Despite the great importance of EE in the development and psychosocial adaptation of affected children, the mechanisms of cognitive deficits in EE have so far been insufficiently investigated. This review article summarizes the various neuroimaging studies which have tried to describe specific neuronal networks in EE. The results show that although epileptic activity in EE can be generated in different brain regions, specific propagation pathways and networks exist which are very characteristic for each different form of encephalopathy. In some forms of EE the epileptic activity seems to impair the integrity of the default mode network and possibly to interfere with cognitive function through this mechanism. Furthermore, there are further mechanisms underlying EE, e.g. abnormal connectivity patterns between brain regions which participate in the control of cognitive functions and impairment of the connections and activities in the thalamocortical network.     

Mandibular advancement device and CPAP upon cardiovascular parameters in OSA

Purpose

This study aims to compare the effects of a mandibular advancement device (MAD) with continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) on blood pressure (BP), oxidative stress, and heart rate variability (HRV) in a randomized, crossed-over, single-blind, and controlled trial.

Methods

Twenty-nine moderate-to-severe adult OSA patients underwent MAD, CPAP, and placebo oral appliance treatment. Polysomnography, Epworth sleepiness scale, 24-h ambulatory BP monitoring, oxidative stress parameters (malondialdehyde, catalase, superoxide dismutase, vitamins C, E, B₆, B₁₂, folate, homocysteine, uric acid), and HRV were assessed at baseline and after 1 month of each treatment. Diaries were used to evaluate compliance for devices and a pressure–time meter for CPAP.

Results

Both active treatments resulted in decreases in apnea and hypopnea index and Epworth sleepiness scale; CPAP showed a greater effect. Frequency of diastolic BP dipping was higher in the MAD group compared with the CPAP group. A significant drop from baseline levels for catalase activity was observed after MAD. For HRV, there was a significant decrease in total power at night with CPAP and MAD compared with POA, and a decrease in index of sleep autonomic variation with MAD compared with baseline levels. Compliance rates were higher with MAD rather than CPAP.

Conclusions

Even though CPAP proved to be more effective at attenuating OSA, better compliance with MAD favored the reduction of one of the enzymes which participates in oxidative stress and better autonomic modulation during sleep.     

Sacral neuromodulation for bowel dysfunction: a consensus statement from the Italian group

Background

Representatives from the Italian centers experienced in sacral neuromodulation (SNM) for the treatment of bowel dysfunction met in order to define the current clinical practice in Italy and to produce a consensus statement regarding indications for this therapy and patient management.

Methods

Fifty Italian colonproctologists were asked to complete a questionnaire concerning their clinical practice in SNM (290 questions, grouped within 4 broad areas). Physicians expressed their opinion by completing the questionnaire, assigning to each statement their level of agreement according to the 5-point Likert scale; the data were analyzed by attributing to each expert’s answers a weight proportional to the degree of experience. During a meeting held 2 months later, the critical aspects of the therapy were re-examined and discussions held with the goal of reaching an agreement on controversial topics. The available literature was reviewed.

Results

Patient selection criteria, etiology, diagnostic investigations, test procedures and implantation, follow-up and evaluation of results have been reviewed. The aim was to achieve an algorithm for patient management, showing the place of SNM in the treatment of bowel dysfunction. The approach in case of treatment failure was also discussed.

Conclusions

Analysis of the data collected reveals substantial consensus at the national level concerning all the main points with regard to the therapy. The recommendations expressed in this article can be considered as national guidelines and taken into account by the principal international implantation centers.