In the Era of mRNA Vaccines,Is There Any Hope for HIV Functional Cure?

Over 36 million people worldwide are infected with HIV. Antiretroviral therapy (ART) has proven to be highly effective to prevent HIV-1 transmission, clinical progression and death. Despite this success, the number of HIV-1 infected individuals continues increasing and ART should be taken for life. Therefore, there are two main priorities: the development of preventive vaccines to protect from HIV acquisition and achieve an efficient control of HIV infection in the absence of ART (functional cure). In this sense, in the last few years, there has been a broad interest in new and innovative approaches such as mRNA-based vaccines. RNA-based immunogens represent a promising alternative to conventional vaccines because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. Some mRNA-based vaccines platforms against infectious diseases have demonstrated encouraging results in animal models and humans. However, their application is still limited because the instability and inefficient in vivo delivery of mRNA. Immunogens, design, immunogenicity, chemical modifications on the molecule or the vaccine delivery methods are all crucial interventions for improvement. In this review we, will present the current knowledge and challenges in this research field. mRNA vaccines hold great promises as part of a combined strategy, for achieving HIV functional cure.     

Pinealectomy interferes with the circadian clock genes expression in white adipose tissue

Melatonin, the main hormone produced by the pineal gland, is secreted in a circadian manner (24‐hr period), and its oscillation influences several circadian biological rhythms, such as the regulation of clock genes expression (chronobiotic effect) and the modulation of several endocrine functions in peripheral tissues. Assuming that the circadian synchronization of clock genes can play a role in the regulation of energy metabolism and it is influenced by melatonin, our study was designed to assess possible alterations as a consequence of melatonin absence on the circadian expression of clock genes in the epididymal adipose tissue of male Wistar rats and the possible metabolic repercussions to this tissue. Our data show that pinealectomy indeed has impacts on molecular events: it abolishes the daily pattern of the expression of Clock, Per2, and Cry1 clock genes and Pparγ expression, significantly increases the amplitude of daily expression of Rev‐erbα, and affects the pattern of and impairs adipokine production, leading to a decrease in leptin levels. However, regarding some metabolic aspects of adipocyte functions, such as its ability to synthesize triacylglycerols from glucose along 24 hr, was not compromised by pinealectomy, although the daily profile of the lipogenic enzymes expression (ATP‐citrate lyase, malic enzyme, fatty acid synthase, and glucose‐6‐phosphate dehydrogenase) was abolished in pinealectomized animals.     

Treatment of oral manifestations of toxic epidermal necrolysis with low‐level laser therapy in a pediatric patient

Drug‐induced reactions are complications associated with high mortality and significant morbidity. Stevens–Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are examples of these conditions, which are characterized by skin and mucous lesions. Here, we report a case of a 9‐year‐old girl who presented with blisters associated with an extensive vesicular rash and multiple ulcerations on the lips and oral cavity. A drug‐induced hypersensitivity reaction to antibiotics was suspected, and a diagnosis of TEN was made. The patient was managed with withdrawal of the suspected causative agent, and the oral lesions were treated with low‐level laser therapy (LLLT) and oral hygiene. This case highlights that TEN requires interdisciplinary intervention with dental assistance and follow‐up to improve symptoms, nutrition, systemic condition, and quality of life.     

Analysis of the EEG dynamics of epileptic activity in gelastic seizures using decomposition in independent components.

OBJECTIVE: Gelastic seizures are a frequent and well established manifestation of the epilepsy associated with hypothalamic hamartomas. The scalp EEG recordings very seldom demonstrate clear spike activity and the information about the ictal epilepsy dynamics is limited. In this work, we try to isolate epileptic rhythms in gelastic seizures and study their generators. METHODS: We extracted rhythmic activity from EEG scalp recordings of gelastic seizures using decomposition in independent components (ICA) in three patients, two with hypothalamic hamartomas and one with no hypothalamic lesion. Time analysis of these rhythms and inverse source analysis was done to recover their foci of origin and temporal dynamics. RESULTS: In the two patients with hypothalamic hamartomas consistent ictal delta (2-3 Hz) rhythms were present, with subcortical generators in both and a superficial one in a single patient. The latter pattern was observed in the patient with no hypothalamic hamartoma visible in MRI. The deep generators activated earlier than the superficial ones, suggesting a consistent sub-cortical origin of the rhythmical activity. CONCLUSIONS: Our data is compatible with early and brief epileptic generators in deep sub-cortical regions and more superficial ones activating later. SIGNIFICANCE: Gelastic seizures express rhythms on scalp EEG compatible with epileptic activity originating in sub-cortical generators and secondarily involving cortical ones.     

Preliminary evaluation of vitiligo using in vivo reflectance confocal microscopy

BACKGROUND: Vitiligo is the most common pigmentary disorder with a global incidence from 0.1% to 2% in different geographical areas. Histopathology and histochemistry have shown the reduction of melanocytes in achromic patches, but microscopic changes of lesional and non-lesional skin are still not completely understood. Reflectance confocal microscopy (RCM), based on the different light reflectance index of cutaneous structures, allowed in vivo, en face microscopic evaluation of superficial skin layers with a resolution similar to skin histology. AIM: The purpose of this study was to evaluate RCM features of lesional and non-lesional skin of vitiligo patients. Moreover, re-pigmented areas were taken into consideration in order to evaluate melanocyte response to ultraviolet B (UVB) radiation. SUBJECTS AND METHODS: Sixteen patients of different phototypes affected by active non-segmental vitiligo and 10 controls were enrolled in the study. In vivo skin imaging was done using a commercially available RCM (Lucid, Vivascope 1500. Re-pigmented areas from 6 to 16 patients (after UVB narrow-band therapy) were also examined. RESULTS: Vitiligo lesions showed the disappearance of the bright rings normally seen at the dermo-epidermal junction. Moreover, non-lesional skin of vitiligo patients showed unexpected changes as the presence of half-rings or scalloped border-like features of the bright papillary rings. In re-pigmented areas after UVB narrow band therapy, the presence of activated, dendritic melanocytes was seen. CONCLUSIONS: Considering our results, and following further studies, RCM clinical applications could be used in the therapeutic monitoring and evaluation of the evolution of vitiligo.     

Is there a genetic susceptibility locus for Parkinson's disease on chromosome 22q13?

The cytochrome P450 mono-oxygenase gene, CYP2D6 on chromosome 22q13 (ch22q13), has been inconsistently associated with Parkinson's disease. Associations with CYP2D6 have either been absent altogether or have involved more than one polymorphism, many of which have the same metabolic effect on gene expression. We examined the association between CYP2D6 polymorphisms and Parkinson's disease in a case-control study and included 10 polymorphic dinucleotide repeat markers linked to CYP2D6 to determine whether the association was present or due to linkage disequilibrium. There was no association between any polymorphism of CYP2D6 and Parkinson's disease, but two of 10 dinucleotide repeat markers linked to CYP2D6 were associated with the disease. These results provide evidence to suggest that there may be an unidentified locus for susceptibility to Parkinson's disease that is in linkage disequilibrium with dinucleotide repeat markers mapping near CYP2D6 on ch22q13.