Optical-thermal mathematical model for endovenous laser ablation of varicose veins

Endovenous laser ablation (EVLA) is successfully used to treat varicose veins. However, the exact working mechanism is still not fully identified and the clinical procedure is not yet standardized. Mathematical modeling of EVLA could strongly improve our understanding of the influence of the various EVLA processes. The aim of this study is to combine Mordon's optical-thermal model with the presence of a strongly absorbing carbonized blood layer on the fiber tip. The model anatomy includes a cylindrically symmetric blood vessel surrounded by an infinite homogenous perivenous tissue. The optical fiber is located in the center of the vessel and is withdrawn with a pullback velocity. The fiber tip includes a small layer of strongly absorbing material, representing the layer of carbonized blood, which absorbs 45 % of the emitted laser power. Heat transfer due to boiling bubbles is taken into account by increasing the heat conduction coefficient by a factor of 200 for temperatures above 95 °C. The temperature distribution in the blood, vessel wall, and surrounding medium is calculated from a numerical solution of the bioheat equation. The simulations were performed in MATLAB? and validated with the aid of an analytical solution. The simulations showed, first, that laser wavelength did virtually not influence the simulated temperature profiles in blood and vessel wall, and, second, that temperatures of the carbonized blood layer varied slightly, from 952 to 1,104 °C. Our improved mathematical optical-thermal EVLA model confirmed previous predictions and experimental outcomes that laser wavelength is not an important EVLA parameter and that the fiber tip reaches exceedingly high temperatures.     

How we started performing endovenous thermal ablation procedures: a personal history

This story is a personal journey of two Dutch dermatologists pioneering in the field of endovenous laser ablation of varicose veins, illustrating how innovations find their way in medicine and, in particular, in surgical specialties. After the introduction of these thermal ablative procedures in 2001, we have fully embraced these minimally invasive techniques, and in the process, we have increased our understanding on its mechanism of action and confirmed the clinical relevance of treating varicose veins with endovenous laser ablation. In 2013, thermal ablation is considered a standard of care by physicians as well as patients with varicose veins.     

Validation of the rat model of cryptogenic infantile spasms

Purpose: To determine whether a new model of cryptogenic infantile spasms consisting of prenatal priming with betamethasone and postnatal trigger of spasms by N‐methyl‐d ‐aspartate (NMDA) responds to chronic adrenocorticotropic hormone (ACTH) treatment, and has electroencephalography (EEG) signature, efficacy of treatments, and behavioral impairments similar to those in human infantile spasms. Methods: Rats prenatally primed with betamethasone on gestational day 15 were used. Spasms were triggered with NMDA between postnatal days (P) 10 and 15 in a single session or in multiple sessions in one subject. The expression of spasms was compared to prenatally saline‐injected controls. Effects of relevant treatments (ACTH, vigabatrin, methylprednisolone, rapamycin) were determined in betamethasone‐primed rats. In the rats after spasms, behavioral evaluation was performed in the open field and elevated plus maze on P20–22. Key Findings: NMDA at P10–15 (the rat “infant” period) triggers the spasms significantly earlier and in greater numbers in the prenatal betamethasone‐exposed brain compared to controls. Similar to human condition, the spasms occur in clusters. Repeated trigger of spasms is associated with ictal EEG electrodecrements and interictal large‐amplitude waves, a possible rat variant of hypsarrhythmia. Chronic ACTH treatment in a randomized experiment, and chronic pretreatment with methylprednisolone significantly suppress the number of spasms similar to the human condition. Pretreatment with vigabatrin, but not rapamycin, suppressed the spasms. Significant behavioral changes occurred following multiple bouts of spasms. Significance: The model of infantile spasms has remarkable similarities with the human condition in semiology, EEG, pharmacologic response, and long‐term outcome. Therefore, the model can be used to search for novel and more effective treatments for infantile spasms.     

A Novel Iron Chelator-Radical Scavenger Ameliorates Motor Dysfunction and Improves Life Span and Mitochondrial Biogenesis in SOD1<Superscript>G93A</Superscript> ALS Mice

The aim of the present study was to evaluate the therapeutic effect of the novel neuroprotective multitarget brain permeable monoamine oxidase inhibitor/iron chelating-radical scavenging drug, VAR10303 (VAR), co-administered with high-calorie/energy-supplemented diet (ced) in SOD1^G93A transgenic amyotrophic lateral sclerosis (ALS) mice. Administration of VAR-ced was initiated after the appearance of disease symptoms (at day 88), as this regimen is comparable with the earliest time at which drug therapy could start in ALS patients. Using this rescue protocol, we demonstrated in the current study that VAR-ced treatment provided several beneficial effects in SOD1^G93A mice, including improvement in motor performance, elevation of survival time, and attenuation of iron accumulation and motoneuron loss in the spinal cord. Moreover, VAR-ced treatment attenuated neuromuscular junction denervation and exerted a significant preservation of myofibril regular morphology, associated with a reduction in the expression levels of genes related to denervation and atrophy in the gastrocnemius (GNS) muscle in SOD1^G93A mice. These effects were accompanied by upregulation of mitochondrial DNA and elevated activities of complexes I and II in the GNS muscle. We have also demonstrated that VAR-ced treatment upregulated the mitochondrial biogenesis master regulator, peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) and increased PGC-1α-targeted metabolic genes and proteins, such as, PPARγ, UCP1/3, NRF1/2, Tfam, and ERRα in GNS muscle. These results provide evidence of therapeutic potential of VAR-ced in SOD1^G93A mice with underlying molecular mechanisms, further supporting the importance role of multitarget iron chelators in ALS treatment.     

Attention-Deficit/Hyperactivity Disorder and Transitional Aged Youth

Purpose of Review

Extensive research has been conducted on attention-deficit/hyperactivity disorder (ADHD) in children and adults; however, less is known about ADHD during the transition from childhood to adulthood. Transitional aged youth (TAY) with ADHD represents a particularly vulnerable population as their newfound independence and responsibility often coincides with the development of comorbid disorders. The purpose of this review is to provide an update on the evaluation, diagnosis, and treatment of TAY-ADHD.

Recent Findings

Recent studies discovering ADHD symptoms emerging in TAY call the classification of ADHD as a disorder necessarily developing in childhood into question. TAY-ADHD are also shown to be vulnerable to academic and social impairments, increased risky behavior, and comorbid psychiatric disorders. Due to the risk of stimulant diversion in TAY, providers are advised to take precaution when prescribing medication to this population. Recent studies demonstrating the efficacy of psychotherapy in conjunction with non-stimulant or extended release stimulant medication provide a feasible alternative.

Summary

This review highlights research on the course and evaluation of ADHD, impairments and comorbidities specific to TAY, and treatments tailored to address the unique challenges associated with TAY-ADHD.

     

Long-lasting sleep patterns of adult patients with minor traumatic brain injury (mTBI) and non-mTBI subjects

BACKGROUND: Sleep disturbance is a common subjective complaint of minor traumatic brain-injured (mTBI) patients, but little is known about the characteristics of sleep disturbance in adults years after the injury. METHODS: Polysomnographic (PSG) and multiple sleep latency test (MSLT) records of 26 mTBI adult patients with normal brain computerized tomography and negative encephalographic studies, no past history of CNS pathology, no premorbid or present major psychiatric diagnosis, and no sleep apnea syndrome were compared to a matched group of apparently healthy individuals (controls). RESULTS: Sleep patterns were disturbed in the mTBI patients. Their sleep architecture was altered, with significantly higher light-sleep non-rapid eye movement (NREM) stage 2 scores compared to controls (54.5+/-13.4% vs. 46.6+/-10.4%, respectively, p=0.03) and significantly lower REM sleep scores (21.2+/-8.4% vs. 25.4+/-4.5%, respectively, p=0.05). The MSLT findings documented significant excessive daytime episodes of falling asleep. CONCLUSIONS: Sleep disturbances of adult patients with chronic mTBI may manifest characteristic alterations in both timing and architecture of their sleep patterns. Sleep lab evaluations may help identify subgroups of mTBI patients who would probably benefit from treatment.     

Schizophrenia-like neurophysiological abnormalities in 22q11.2 deletion syndrome and their association to COMT and PRODH genotypes

22q11.2 deletion syndrome (22q11.2DS) is a common genetic risk factor for the development of schizophrenia. We investigated two neurophysiological endophenotypes of schizophrenia – P50 sensory gating and mismatch negativity in 22q11.2DS subject and evaluated their association with catechol O-methyltransferase (COMT) and proline dehydrogenase (PRODH) genetic variants. We also assessed the association of neurophysiological measures with schizophrenia-like symptomatology in 22q11.2DS. Fifty-nine subjects, 41 with 22q11.2DS and 18 typically developing controls, participated in the study. The participants with 22q11.2DS were genotyped for the COMT Val¹⁵⁸Met (rs4680) and PRODH Gln¹⁹Pro (rs2008720) and Arg¹⁸⁵Trp (rs4819756) polymorphisms. Following psychiatric evaluation, all the participants underwent neurophysiological recordings and executive function assessment. The 22q11.2DS group showed poorer sensory gating of the P50 response than the controls. Within the 22q11.2DS group, the COMT Met allele was associated with poorer sensory gating, while both the COMT Met allele and the PRODH Pro-Arg haplotype were associated with smaller mismatch negativity amplitudes. Smaller mismatch negativity amplitudes predicted greater impairment of executive functions and greater severity of schizophrenia-like negative symptoms in 22q11.2DS. The current study demonstrates that sensory gating impairments that are typical of schizophrenia are found in 22q11.2DS subjects. Our results further suggest that COMT and PRODH genetic variations contribute to sensory gating and mismatch negativity schizophrenia-like impairments in 22q11.2DS, possibly via dopaminergic/glutamatergic networks. The associations of mismatch negativity impairments with increased severity of schizophrenia-like negative symptoms and poorer executive functions performance in our 22q11.2DS sample suggest that mismatch negativity is a potential endophenotype for schizophrenia in 22q11.2DS.