Crigler-Najjar syndrome: looking to the future does not make us forget the present.

Recently, the safety and efficacy of gene therapy were evaluated in patients with Crigler-Najjar syndrome (CNS). Although it is a promising curative option for CNS, many doubts still persist about its long-term efficacy and safety. Furthermore, there is a risk of overlooking several unresolved problems still present in current clinical practice. This letter is a call for action on crucial open issues that remain nowadays an unmet need in the management of CNS patients.

Randomised Clinical Trial: Calorie Restriction Regimen with Tomato Juice Supplementation Ameliorates Oxidative Stress and Preserves a Proper Immune Surveillance Modulating Mitochondrial Bioenergetics of T-Lymphocytes in Obese Children Affected by Non-Alcoholic Fatty Liver Disease (NAFLD).

Fatty liver disease is a serious complication of childhood obesity. Calorie-restricted regimen (RCR) is one of the effective therapy for this condition. Aim of the study was to evaluate the effect of lycopene-rich tomato sauce with oregano and basil extracts in obese children with fatty liver on RCR. 61 obese children with fatty liver were enrolled, 52 completed the study. A randomized cross over clinical trial was performed. Participants were assigned to RCR alone or with a supplement of lycopene-rich tomato juice for 60 days; subsequently, the groups were switched to the alternative regimen for the next 60 days. Reduction in BMI, HOMA-IR, cholesterol, triglycerides, liver size, and steatosis was more profound in tomato-supplemented group. Leptin decreased in both groups whereas adiponectin raised only after tomato supplementation. RCR is associated with the impaired engagement of T-cells glycolysis and proliferation, tomato-supplementation resulted in glycolytic metabolic activation of T-cells. Tomato juice ameliorates glucose and lipid metabolism in obese children, improve oxidative and inflammatory state and modulates the mitochondrial metabolism of T-cells contributing to a maintenance of a proper immune surveillance in children, impaired by RCR. The addition of tomato to RCR could be considered a protective and preventive support to obese child.

Unilateral and Multiple Cavitation Sounds During Lumbosacral Spinal Manipulation.

OBJECTIVE: The purpose of this study was to determine from which side of the spine the popping sound (PS) emanates during side-lying, rotatory high-velocity low-amplitude (HVLA) thrust manipulation directed to the L5-S1 articulation using a time-frequency analysis. Secondary aims were to calculate the average number of PSs, the duration of lumbar thrust manipulation, and the duration of a single PS. METHODS: Thirty-four asymptomatic participants received 2 lumbar HVLA thrust manipulations targeting the right and left L5-S1 articulations. Two high sampling rate accelerometers were secured bilaterally 25 mm lateral to the midline of the L5-S1 interspace. For each manipulation, 2 audio signals were extracted and singularly processed via spectrogram calculation to obtain the release of energy over time on each side of the lumbosacral junction. RESULTS: During 60 HVLA thrust manipulations, it was measured a total of 320 PSs. Of those PSs, 176 occurred ipsilateral and 144 occurred contralateral to the targeted L5-S1 articulation; that is, the PS was no more likely to occur on the upside than the downside facet after right or left rotatory L5-S1 HVLA thrust manipulation. Moreover, PSs occurring on both sides at the same time were detected very rarely (ie, 2% of cases) with the lumbar HVLA thrust manipulations. The mean number of audible PSs per lumbosacral HVLA thrust manipulation was 5.27 (range 2-9). The mean duration of a single manipulation was 139.13 milliseconds (95% confidence interval: 5.61-493.79), and the mean duration of a single PS was 2.69 milliseconds (95% confidence interval: 0.95-4.59). CONCLUSION: Based on our findings, spinal manipulative therapy practitioners should expect multiple PSs that most often occur on the upside or the downside facet articulations when performing HVLA thrust manipulation to the lumbosacral junction (ie, L5-S1). However, whether the multiple PSs found in this study emanated from the same joint or adjacent ipsilateral or contralateral facet joints remains unknown. A single model may not necessarily be able to explain all of the audible sounds during HVLA thrust manipulation.

Copper deficiency myelopathy: A report of two cases.

CONTEXT: Copper deficiency myelopathy represents an often underdiagnosed, acquired neurological syndrome, clinically characterized by posterior column dysfunction. The main causes of copper deficiency are bariatric surgery, increased consumption of zinc, and malabsorption. However, even after a careful history taking and extensive laboratory researches, the etiology of copper deficiency remains undetermined in a significant percentage of cases. Patients affected by copper deficiency myelopathy usually present with sensory ataxia due to dorsal column dysfunction and sometimes with mild leg spasticity. In such patients, spinal cord magnetic resonance imaging (MRI) may show hyperintense lesions in T2-weighted sequences involving the posterior columns of cervical and thoracic cord. These MRI findings are not distinguishable from those of subacute combined degeneration associated with vitamin B12 deficiency. FINDINGS: Here, we describe two patients with gait ataxia and sensory symptoms in which a diagnosis of copper deficiency myelopathy was made. Both patients showed a significant clinical, neuroradiological, and neurophysiological improvement after proper supplementation therapy. CONCLUSION: The patients herein described underline the importance to include serum copper and ceruloplasmin levels as part of the myelopathy diagnostic workup, especially in the cases of otherwise unexplained subacute myelopathy involving the posterior columns. Since copper deficiency myelopathy is a progressive syndrome, early diagnosis is mandatory in order to promptly provide a proper supplementation therapy and, thus, prevent an irreversible neurological damage.