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1.
Nature ; 609(7925): 94-100, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36002567

RESUMEN

Bipedal locomotion is one of the key adaptations that define the hominin clade. Evidence of bipedalism is known from postcranial remains of late Miocene hominins as early as 6 million years ago (Ma) in eastern Africa1-4. Bipedality of Sahelanthropus tchadensis was hitherto inferred about 7 Ma in central Africa (Chad) based on cranial evidence5-7. Here we present postcranial evidence of the locomotor behaviour of S. tchadensis, with new insights into bipedalism at the early stage of hominin evolutionary history. The original material was discovered at locality TM 266 of the Toros-Ménalla fossiliferous area and consists of one left femur and two, right and left, ulnae. The morphology of the femur is most parsimonious with habitual bipedality, and the ulnae preserve evidence of substantial arboreal behaviour. Taken together, these findings suggest that hominins were already bipeds at around 7 Ma but also suggest that arboreal clambering was probably a significant part of their locomotor repertoire.


Asunto(s)
Evolución Biológica , Marcha , Hominidae , Cráneo , Animales , Chad , Fósiles , Hominidae/anatomía & histología , Hominidae/fisiología , Cráneo/anatomía & histología , Árboles
2.
J Physiol ; 602(7): 1273-1295, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38513000

RESUMEN

Vision relies on the continuous exchange of material between the photoreceptors, retinal pigment epithelium and choriocapillaris, a dense microvascular bed located underneath the outer retina. The anatomy and physiology of the choriocapillaris and their association with retinal homeostasis have proven difficult to characterize, mainly because of the unusual geometry of this vascular bed. By analysing tissue dissected from 81 human eyes, we show that the thickness of the choriocapillaris does not vary significantly over large portions of the macula or with age. Assessments of spatial variations in the anatomy of the choriocapillaris in three additional human eyes indicate that the location of arteriolar and venular vessels connected to the plane of the choriocapillaris is non-random, and that venular insertions cluster around arteriolar ones. Mathematical models built upon these anatomical analyses reveal that the choriocapillaris contains regions where the transport of passive elements is dominated by diffusion, and that these diffusion-limited regions represent areas of reduced exchange with the outer retina. The width of diffusion-limited regions is determined by arterial flow rate and the relative arrangement of arteriolar and venular insertions. These analyses demonstrate that the apparent complexity of the choriocapillaris conceals a fine balance between several anatomical and functional parameters to effectively support homeostasis of the outer retina. KEY POINTS: The choriocapillaris is the capillary bed supporting the metabolism of photoreceptors and retinal pigment epithelium, two critical components of the visual system located in the outer part of the retina. The choriocapillaris has evolved a planar multipolar vascular geometry that differs markedly from the branched topology of most vasculatures in the human body. Here, we report that this planar multipolar vascular geometry is associated with spatially heterogenous molecular exchange between choriocapillaris and outer retina. Our data and analyses highlight a necessary balance between choriocapillaris anatomical and functional parameters to effectively support homeostasis of the outer retina.


Asunto(s)
Coroides , Retina , Humanos , Coroides/irrigación sanguínea , Vasos Retinianos , Capilares , Arteriolas
3.
Proc Natl Acad Sci U S A ; 118(30)2021 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-34301870

RESUMEN

Genome-wide association studies have identified the chromosome 10q26 (Chr10) locus, which contains the age-related maculopathy susceptibility 2 (ARMS2) and high temperature requirement A serine peptidase 1 (HTRA1) genes, as the strongest genetic risk factor for age-related macular degeneration (AMD) [L.G. Fritsche et al., Annu. Rev. Genomics Hum. Genet. 15, 151-171, (2014)]. To date, it has been difficult to assign causality to any specific single nucleotide polymorphism (SNP), haplotype, or gene within this region because of high linkage disequilibrium among the disease-associated variants [J. Jakobsdottir et al. Am. J. Hum. Genet. 77, 389-407 (2005); A. Rivera et al. Hum. Mol. Genet. 14, 3227-3236 (2005)]. Here, we show that HTRA1 messenger RNA (mRNA) is reduced in retinal pigment epithelium (RPE) but not in neural retina or choroid tissues derived from human donors with homozygous risk at the 10q26 locus. This tissue-specific decrease is mediated by the presence of a noncoding, cis-regulatory element overlapping the ARMS2 intron, which contains a potential Lhx2 transcription factor binding site that is disrupted by risk variant rs36212733. HtrA1 protein increases with age in the RPE-Bruch's membrane (BM) interface in Chr10 nonrisk donors but fails to increase in donors with homozygous risk at the 10q26 locus. We propose that HtrA1, an extracellular chaperone and serine protease, functions to maintain the optimal integrity of the RPE-BM interface during the aging process and that reduced expression of HTRA1 mRNA and protein in Chr10 risk donors impairs this protective function, leading to increased risk of AMD pathogenesis. HtrA1 augmentation, not inhibition, in high-risk patients should be considered as a potential therapy for AMD.


Asunto(s)
Predisposición Genética a la Enfermedad , Serina Peptidasa A1 que Requiere Temperaturas Altas/metabolismo , Degeneración Macular/genética , Epitelio Pigmentado de la Retina/metabolismo , Coroides/metabolismo , Variación Genética , Serina Peptidasa A1 que Requiere Temperaturas Altas/genética , Humanos , Desequilibrio de Ligamiento , ARN Mensajero/genética , ARN Mensajero/metabolismo , Retina/metabolismo
4.
Ecotoxicol Environ Saf ; 280: 116522, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38843743

RESUMEN

This study aimed to evaluate the effect of adding liquid extract of algae (Hypnea musciformis, Grateloupia acuminata, and Sargassum muticum) (HGS) and Magnesium oxide nanoparticles (MgO NPs) using this extract to rear water of Oreochromis niloticus, on improving culture water indices, growth performance, digestive enzyme, hemato-biochemical characters, immune, antioxidative responses, and resistance after challenged by Aeromonas hydrophila with specific refer to the potential role of the mixture in vitro as resistance against three strains bacteria (Aeromonas sobria, Pseudomonas fluorescens, P. aeruginosa) and one parasite (Cichlidogyrus tilapia). The first group represented control, HGS0, whereas the other group, HGS5, HGS10, and HGS15 mL-1 of liquid extract, as well as all groups with 7.5 µg mL-1 MgO-NPs added to culture water of O. niloticus, for 60 days. Data showed that increasing levels at HGS 10 and HGS15 mL-1 in to-culture water significantly enhanced growth-stimulating digestive enzyme activity and a significantly improved survival rate of O. niloticus after being challenged with A. hydrophila than in the control group. The total viability, coliform, fecal coliform count, and heavy metal in muscle partially decreased at HGS 10 and HGS15 mL-1 than in the control group. Correspondingly, the highest positive effect on hemato-biochemical indices was noticed at levels HGS 10 and HGS15 mL-1. Fish noticed an improvement in immune and antioxidant indices compared to control groups partially at HGS 10 and HGS15 mL-1. Interestingly, fish cultured in rearing water with the mixture provided downregulated the related inflammatory genes (HSP70, TNF, IL-1ß, and IL-8) partially at HGS15 mL-1. In vitro, the mixture showed positive efficiency as an antibacterial and partially antiparasitic at HGS 10 and HGS15 mL-1. This study proposes utilizing a mixture of (HGS) and (MgO-NPs) with optimum levels of 10-15 mL-1 in cultured water to improve water indices, growth, health status, and increased resistance of O. niloticus against bacterial and parasitic infection.


Asunto(s)
Cíclidos , Resistencia a la Enfermedad , Óxido de Magnesio , Calidad del Agua , Animales , Óxido de Magnesio/farmacología , Cíclidos/inmunología , Resistencia a la Enfermedad/efectos de los fármacos , Algas Marinas , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/química , Nanopartículas , Tecnología Química Verde , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/química , Aeromonas hydrophila/efectos de los fármacos , Sargassum
5.
Fortschr Neurol Psychiatr ; 91(10): 404-413, 2023 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-35948023

RESUMEN

Alexithymia is a multidimensional construct of personality implicating difficulties in identifying and describing another's feelings, and externally oriented thinking. It is broadly reported in psychiatric patients but has gained little attention regarding its occurrence and pathophysiology in multiple sclerosis (MS). This narrative review aims to address prevalence, etiology, neurobiological, and clinical findings of alexithymia. The prevalence of alexithymia in MS ranges from 10 to 53%. There seems to be an association with anxiety, depression, fatigue, and some aspects of social cognition, while the relationship with clinical and classical cognitive variables was rarely evaluated. Only a few studies referred to its pathophysiology assuming an aberrant interhemispheric transfer or regional cerebral abnormalities. The prevalence of alexithymia in MS and the potential negative impact on quality of life and interpersonal communication could severely impact clinical MS management and a screnning for these factors should be mandatory. Thus, further evaluation is needed concerning its relationship with clinical, emotional, and cognitive confounders. Large-scale studies employing neuroimaging techniques are needed for a better understanding of the neural underpinnings of this MS feature.


Asunto(s)
Síntomas Afectivos , Esclerosis Múltiple , Humanos , Síntomas Afectivos/epidemiología , Síntomas Afectivos/etiología , Síntomas Afectivos/psicología , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/epidemiología , Calidad de Vida , Emociones , Ansiedad
6.
Hum Genomics ; 15(1): 60, 2021 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-34563268

RESUMEN

BACKGROUND: Single-variant associations with age-related macular degeneration (AMD), one of the most prevalent causes of irreversible vision loss worldwide, have been studied extensively. However, because of a lack of refinement of these associations, there remains considerable ambiguity regarding what constitutes genetic risk and/or protection for this disease, and how genetic combinations affect this risk. In this study, we consider the two most common and strongly AMD-associated loci, the CFH-CFHR5 region on chromosome 1q32 (Chr1 locus) and ARMS2/HTRA1 gene on chromosome 10q26  (Chr10 locus). RESULTS: By refining associations within the CFH-CFHR5 locus, we show that all genetic protection against the development of AMD in this region is described by the combination of the amino acid-altering variant CFH I62V (rs800292) and genetic deletion of CFHR3/1. Haplotypes based on CFH I62V, a CFHR3/1 deletion tagging SNP and the risk variant CFH Y402H are associated with either risk, protection or neutrality for AMD and capture more than 99% of control- and case-associated chromosomes. We find that genetic combinations of CFH-CFHR5 haplotypes (diplotypes) strongly influence AMD susceptibility and that individuals with risk/protective diplotypes are substantially protected against the development of disease. Finally, we demonstrate that AMD risk in the ARMS2/HTRA1 locus is also mitigated by combinations of CFH-CFHR5 haplotypes, with Chr10 risk variants essentially neutralized by protective CFH-CFHR5 haplotypes. CONCLUSIONS: Our study highlights the importance of considering protective CFH-CFHR5 haplotypes when assessing genetic susceptibility for AMD. It establishes a framework that describes the full spectrum of AMD susceptibility using an optimal set of single-nucleotide polymorphisms with known functional consequences. It also indicates that protective or preventive complement-directed therapies targeting AMD driven by CFH-CFHR5 risk haplotypes may also be effective when AMD is driven by ARMS2/HTRA1 risk variants.


Asunto(s)
Proteínas del Sistema Complemento/genética , Serina Peptidasa A1 que Requiere Temperaturas Altas/genética , Degeneración Macular/genética , Proteínas/genética , Anciano , Cromosomas/genética , Factor H de Complemento/genética , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos/genética , Humanos , Desequilibrio de Ligamiento , Degeneración Macular/patología , Masculino , Polimorfismo de Nucleótido Simple/genética
7.
Clin Rehabil ; 36(1): 51-58, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34296639

RESUMEN

OBJECTIVE: To investigate whether adding neural mobilization to a standard postoperative physical therapy program could improve the outcomes of patients after lumbar laminectomy. DESIGN: A single blinded randomized controlled trial. SETTING: Outpatient setting. PARTICIPANTS: Sixty participants of both sexes who had undergone lumbar laminectomy. INTERVENTIONS: Participants were allocated randomly to two groups; study and control groups. All patients received a standard postoperative physical therapy program. Those in the study group received additional neural mobilization in the form of straight leg raising and dorsiflexion with two-ended slider. Treatment was administered three times/week for six successive weeks. OUTCOME MEASURES: Visual analog scale (VAS), Oswestry disability index (ODI), and H-reflex latency were measured pre and post-treatment. RESULTS: The mean age of participants was 44.23 ± 4.64 and 45.3 ± 5.3 in study and control groups respectively (P > 0.05). There were statistically significant differences in VAS, ODI, and H-reflex latency in favor of the study group (P < 0.05). The mean ± SD for VAS, ODI, and H-reflex latency pre vs post treatment was 6.13 ± 1.22 vs 1.40 ± 0.77, 64.46 ± 4.05 vs 16.86 ± 2.55, and 32.07 ± 2.76 vs 27.46 ±1.79 in study group and 5.86 ± 1.07 vs 2.46 ± 0.73, 63.93 ± 3.91 vs 23.40 ± 2.93, and 31.76 ± 2.69 vs 29.4 ± 1.94 in control group, respectively. CONCLUSIONS: Neural mobilization combined with traditional physical therapy program achieved better improvement in pain, functional disability and H-reflex in patients who underwent decompressive laminectomy than traditional physical therapy program only.


Asunto(s)
Reflejo H , Laminectomía , Femenino , Humanos , Vértebras Lumbares , Masculino , Dolor , Modalidades de Fisioterapia , Resultado del Tratamiento
8.
Clin Rehabil ; 35(8): 1142-1150, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33611923

RESUMEN

OBJECTIVE: To assess the effectiveness of Transcutaneous Electrical Nerve Stimulation (TENS) combined with selected physical therapy exercise program on male patients with pudendal neuralgia. DESIGN: A double-blinded randomized controlled study. SETTING: Out-patient setting. PARTICIPANTS: Fifty-two male participants with pudendal neuralgia (30-50 years) were allocated randomly into two groups; study and control. The same physical therapy exercises were applied to all participants, plus the same prescribed analgesic medication (Etodolac). Participants in the study group received additional TENS and sham TENS were given to those in control group. INTERVENTION: Intervention lasted for 12 weeks, three sessions per week (60 minutes/session). OUTCOME MEASURES: Numerical pain rating scale and daily Etodolac intake dose were measured before and after intervention. RESULTS: Statistically significant differences were detected in numerical pain rating scale and daily Etodolac intake in favor of the study group (P < 0.05). After 12 weeks of intervention, the mean ± SD for numerical pain rating scale and daily Etodolac intake were 4.25 ± 1.9 and 259.25 ± 84.4 mg, in the study group, and 6.22 ± 2.22 and 355.55 ± 93.36 mg in the control group, respectively. The mean difference (95% CI) for numerical pain rating scale and daily Etodolac intake was -1.97 (-3.09: -0.83) and -96.3 (-144.9: -47.69), between groups post treatment, respectively. CONCLUSION: Adding TENS to physical therapy exercise program is more effective than physical therapy program alone in improving pain in male patients with pudendal neuralgia as measured by numerical pain rating scale and daily analgesic intake dose.


Asunto(s)
Terapia por Ejercicio , Modalidades de Fisioterapia , Neuralgia del Pudendo/terapia , Estimulación Eléctrica Transcutánea del Nervio , Adulto , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
9.
J Integr Neurosci ; 20(3): 745-754, 2021 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-34645108

RESUMEN

Fatigue is a frequent and debilitating symptom in patients with multiple sclerosis (MS). Affective manifestations are also of high prevalence in this population and can drastically impact the patients' functioning. A considerable proportion of patients with MS suffer from cognitive deficits affecting general and social cognitive domains. In addition, pain in MS is commonly observed in neurology wards, could be of different types, and may result from or be exacerbated by other MS comorbidities. These complaints tend to cluster together in some patients and seem to have a complex pathophysiology and a challenging management. Exploring the effects of new interventions could improve these outcomes and ameliorate the patients' quality of life. Neurofeedback (NFB) might have its place in this context by enhancing or reducing the activity of some regions in specific electroencephalographic bands (i.e., theta, alpha, beta, sensorimotor rhythm). This work briefly revisits the principles of NFB and its application. The published data are scarce and heterogeneous yet suggest preliminary evidence on the potential utility of NFB in patients with MS (i.e., depression, fatigue, cognitive deficits and pain). NFB is simple to adapt and easy to coach, and its place in the management of MS symptoms merits further investigations. Comparing different NFB protocols (i.e., cortical target, specific rhythm, session duration and number) and performing a comprehensive evaluation could help developing and optimizing interventions targeting specific symptoms. These aspects could also open the way for the association of this technique with other approaches (i.e., brain stimulation, cognitive rehabilitation, exercise training, psychotherapies) that have proved their worth in some MS domains.


Asunto(s)
Ansiedad/terapia , Ondas Encefálicas , Dolor Crónico/terapia , Disfunción Cognitiva/terapia , Depresión/terapia , Esclerosis Múltiple/terapia , Neurorretroalimentación/métodos , Ansiedad/etiología , Ondas Encefálicas/fisiología , Dolor Crónico/etiología , Disfunción Cognitiva/etiología , Depresión/etiología , Humanos , Esclerosis Múltiple/complicaciones
10.
J Neural Transm (Vienna) ; 127(6): 953-961, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32161992

RESUMEN

Fatigue is a frequent and debilitating symptom in patients with central nervous system diseases. Up to 90% of patients with multiple sclerosis (MS) suffer from fatigue that drastically affects the quality of life. MS patients also complain of anxiety and depressive symptoms and these three manifestations tend to cluster together in this clinical population. The objective of this work was to assess the effects of transcranial direct stimulation (tDCS), a noninvasive brain stimulation technique, on fatigue as well as anxiety and depressive symptoms. Eleven fatigued MS patients randomly received two blocks (active and sham tDCS) of five consecutive daily sessions of bifrontal tDCS (anode/cathode over the left/right prefrontal cortices, respectively) in a crossover manner, separated by a 3-week washout interval. Evaluation took place at day 1, day 5 (right after each block) and 1 week later. Active but not sham tDCS resulted in a significant improvement of fatigue at day 5 (p < 0.05), an effect that seems to last at least 1 week following the stimulation (p = 0.05). Active tDCS also significantly improved anxiety symptoms, but the effect emerged 1 week later (p < 0.05). No significant effects were obtained regarding depression (p > 0.05). Bifrontal tDCS seems to modulate fatigue in PwMS. The observed anxiolytic effects could constitute delayed after effects of tDCS or might be mediated by fatigue improvement. These findings merit to be addressed in large-scale controlled trials.


Asunto(s)
Esclerosis Múltiple , Estimulación Transcraneal de Corriente Directa , Método Doble Ciego , Fatiga/etiología , Fatiga/terapia , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/terapia , Corteza Prefrontal , Calidad de Vida , Resultado del Tratamiento
11.
J Neural Transm (Vienna) ; 127(8): 1177-1183, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32596749

RESUMEN

Fatigue stands among the most debilitating multiple sclerosis (MS) manifestations. Several pathophysiological mechanisms have been proposed at its origin. However, unmet needs still exist, and further investigations are required to better understand and manage this complaint. A new imaging modality-the phosphorous magnetic resonance spectroscopy (31P-MRS)-might help studying fatigue by allowing the measurement of energy metabolites of various cerebral regions. Therefore, this work aimed to explore the association between fatigue and brain energy status. Thirty MS patients with progressive disease forms completed the study. Their sociodemographic and clinical data including fatigue and disability scores [i.e., Fatigue Severity Scale (FSS) and Expanded Disability Status Scale (EDSS)] were collected. 31P-MRS spectra of (1) bilateral frontoparietal area and (2) centrum semiovale normal appearing white matter (NAWM) were obtained. Percentages of phosphocratine and ß-adenosine triphosphate (ß-ATP) were calculated. FSS scores were found to be directly correlated with the frontoparietal ß-ATP % (p < 0.05). However, there were no significant correlations between FSS scores and NAWM energy metabolites or clinical data (i.e., age, EDSS scores or disease duration). These findings point toward the existence of a link between fatigue severity and the amount of cerebral ATP metabolites. Such a link might reflect either a high production or low utilization of ATP, both of which were paralleled with increased fatigue perception. While the former would be due to a redistribution of ion channels along demyelinated axons and subsequent changes in mitochondrial activity; the latter could be interpreted in the light of neuronal loss which would lead to a decrease in ATP utilization and accumulation of its metabolites.


Asunto(s)
Esclerosis Múltiple , Encéfalo/diagnóstico por imagen , Fatiga/diagnóstico por imagen , Fatiga/etiología , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico por imagen , Fósforo
12.
Cogn Behav Neurol ; 33(2): 90-102, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32496294

RESUMEN

Multiple sclerosis (MS) is the most common inflammatory neurologic disease in young adults. Its pathological mechanisms include demyelination, neurodegeneration, and synaptopathy. Cognitive deficits occur in up to 65% of individuals with MS and affect both nonsocial (eg, information processing speed, memory, and executive functions) and social (ie, emotion recognition, theory of mind, and empathy) cognitive domains. In the last 3 decades, there has been a growing interest in social cognition and its relationship with neuropsychological, sociodemographic, and disease characteristics in individuals with MS. Uncovering the neuropathological correlates of social cognitive deficits is now a crucial aim that would also help us better understand the underlying mechanisms of social cognition. We reviewed 11 neuroimaging studies to investigate social cognition in MS. These studies focused mainly on facial emotion recognition and theory of mind, with the findings suggesting that a disrupted cortico-subcortical network forms the basis of social deficits involving both domains. We then interpreted these results in the context of multiple disconnection syndrome, which occurs as a result of axonal demyelination and degeneration within the connexome of several neural hubs devoted to social cognition. Heterogeneity in social cognitive performance, observed among our study participants, is discussed with reference to the cognitive reserve and brain reserve hypotheses. These reserves may explain why individuals with comparable clinical characteristics of MS may exhibit different cognitive profiles. Further research is required to generalize these findings to the MS population and to inform the development of effective interventions to improve psychosocial functioning in individuals with MS.


Asunto(s)
Encéfalo/patología , Esclerosis Múltiple/psicología , Neuroimagen/métodos , Femenino , Humanos , Masculino , Esclerosis Múltiple/diagnóstico por imagen
13.
Medicina (Kaunas) ; 55(5)2019 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-31126152

RESUMEN

Varicella-zoster virus (VZV) is a human neurotropic herpes virus that causes chickenpox in children. After becoming latent in dorsal root ganglia, it can reactivate to cause dermatological manifestations, the most common one being shingles or herpes zoster. Severe neurologic dysfunctions can occur in immunocompromised patients such as encephalitis, meningitis, myelitis and neuropathy. Longitudinal extensive transverse myelitis (LETM) is an unusual neurological complication mainly described in immunocompromised patients, with very few cases described in immunocompetent ones. We hereby report a case of VZV-induced LETM in an immunocompetent older adult-a situation rarely described in the literature. LETM is a rare complication of VZV and its pathogenesis; therapeutic interventions and prognosis are far from being fully clarified. However, a prompt diagnosis is needed to allow a rapid initialization of treatment and ensure a better outcome. Although the therapeutic lines are not clear, immunosuppressive agents may have their place in cases of unsuccessful results and/or relapses following acyclovir coupled with a well conducted methylprednisolone therapy. Further studies are highly needed to improve the current understanding of the disease course and mechanisms, and to optimize therapeutic strategies.


Asunto(s)
Huésped Inmunocomprometido/inmunología , Mielitis Transversa/complicaciones , Anciano , Herpesvirus Humano 3 , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Mielitis Transversa/diagnóstico por imagen , Mielitis Transversa/virología , Recurrencia , Médula Espinal/diagnóstico por imagen , Médula Espinal/virología
14.
Ann Oncol ; 29(3): 731-736, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29236943

RESUMEN

Background: Concomitant chemotherapy (CT)-radiotherapy (RT) is a standard of care in locally advanced nasopharyngeal carcinoma (NPC) and a role for induction CT is not established. Methods: Patients with locally advanced NPC, WHO type 2 or 3, were randomized to induction TPF plus concomitant cisplatin-RT or concomitant cisplatin-RT alone. The TPF regimen consisted of three cycles of Docetaxel 75 mg/m2 day 1; cisplatin 75 mg/m2 day 1; 5FU 750 mg/m2/day days 1-5. RT consisted of 70 Gy in 7 weeks plus concomitant cisplatin 40 mg/m2 weekly. Results: A total of 83 patients were included in the study. Demographics and tumour characteristics were well balanced between both arms. Most of the patients (95%) in the TPF arm received three cycles of induction CT. The rate of grade 3-4 toxicity and the compliance (NCI-CTCAE v3) during cisplatin-RT were not different between both arms. With a median follow-up of 43.1 months, the 3-year PFS rate was 73.9% in the TPF arm versus 57.2% in the reference arm [hazard ratio (HR) = 0.44; 95% confidence interval (CI): 0.20-0.97, P = 0.042]. Similarly the 3 years overall survival rate was 86.3% in the TPF arm versus 68.9% in the reference arm (HR = 0.40; 95% CI: 0.15-1.04, P = 0.05). Conclusion: In conclusion, several important aspects can be emphasized: the compliance to induction TPF was good and TPF did not compromise the tolerance of the concomitant RT-cisplatin phase. The improved PFS and overall survival rates needs to be confirmed by further trials.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioterapia de Inducción/métodos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioradioterapia/métodos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Docetaxel/administración & dosificación , Docetaxel/efectos adversos , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Quimioterapia de Inducción/efectos adversos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/radioterapia
15.
J Pediatr Hematol Oncol ; 40(3): 182-187, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29462000

RESUMEN

BACKGROUND: ß-thalassemia major (BTM) is an inherited blood disorder leading to severe anemia. A better understanding of BTM complications can be considered an important factor in developing effective health care provision. METHOD: A descriptive exploratory design was used to identify the clinical burden of BTM from affected children's perspective. A convenience sample of 45 patients with BTM, accompanied by a family member, was recruited from a governmental hospital during April-May 2015. RESULTS: The most reported clinical burden was facial deformity 86.9%, followed by systematic infection (48.8%), growth delay (44.4%), and liver problems (39.9%). Patient age was significantly associated with clinical burdens such as bone pain and facial deformity. The number of blood transfusions received was associated with growth delay and bone pain. CONCLUSION: This study highlights the clinical burdens of thalassemia on affected children, in terms of physical appearance, growth delay and other burdens.


Asunto(s)
Talasemia beta/complicaciones , Adolescente , Niño , Preescolar , Costo de Enfermedad , Femenino , Humanos , Lactante , Masculino
16.
Climacteric ; 21(2): 174-178, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29347848

RESUMEN

OBJECTIVE AND DESIGN: Prospective randomized controlled trial to test the effectiveness of topical oxytocin gel to improve vaginal atrophy in postmenopausal women. PATIENTS AND METHODS: A total of 140 postmenopausal women presenting with vaginal atrophy and who satisfied the inclusion and exclusion criteria were randomized into two groups each of 70 patients; they received intravaginal oxytocin gel or placebo gel for 30 days. Serum estrogen level, visual, colposcopic and histological vaginal examination were performed before and after treatment. RESULTS: Forty-seven out of 70 women in the oxytocin gel group improved after treatment and none in the placebo group (p = 0.001). Forty-five participants in the oxytocin group and seven in the placebo group reported relief of dyspareunia (p = 0.001). Thirty-four participants in the oxytocin group and seven in the placebo group reported relief of soreness (p = 0.001). There was no significant difference between the circulating levels of estradiol in both groups before and after treatment (p = 0.4 and 0.6 for the oxytocin group and the placebo group, respectively). CONCLUSION: Oxytocin gel is useful in the restoration of the vaginal epithelium in cases of postmenopausal atrophic vaginitis. Further studies with a longer follow-up period are required to test the long-term effects of oxytocin as a treatment for vaginal atrophy.


Asunto(s)
Oxitócicos/uso terapéutico , Oxitocina/uso terapéutico , Posmenopausia , Enfermedades Vaginales/tratamiento farmacológico , Administración Intravaginal , Atrofia , Dispareunia , Egipto , Epitelio/patología , Estradiol/sangre , Femenino , Humanos , Persona de Mediana Edad , Oxitócicos/sangre , Oxitocina/sangre , Estudios Prospectivos , Método Simple Ciego , Vagina/patología , Enfermedades Vaginales/patología
17.
J Antimicrob Chemother ; 72(6): 1812-1817, 2017 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-28333257

RESUMEN

Objectives: Heterogeneously resistant vancomycin-intermediate coagulase-negative staphylococci (hVICoNS) are emerging pathogens causing central-line-associated bloodstream infections (CLABSIs) in neonatal intensive care unit (NICU) patients. Given the burden of disease associated with CLABSI and the current lack of therapeutic guidelines, we aimed to compare the effectiveness of linezolid versus vancomycin used as the definitive antibiotic therapy for hVICoNS CLABSI. Methods: We performed a retrospective cohort study of infants with hVICoNS CLABSI from a single NICU between 2009 and 2014, treated with either linezolid or vancomycin as definitive antibiotic therapy. CLABSI duration, early and late recurrence and in-hospital mortality were compared using propensity score-adjusted proportional hazards and logistic regression models. Results: Of 89 infants with hVICoNS CLABSI, 33 (37.1%) treated with linezolid were compared with 56 (62.9%) treated with vancomycin. The median duration of CLABSI was 5 (range 1-12) versus 4 days (range 0-14) ( P = 0.11), early recurrences were 3.0% versus 7.1% ( P = 0.42), late recurrences 0% versus 14.3% ( P = 0.02) and mortality 27.3% versus 28.6% ( P = 0.90), when treated with linezolid versus vancomycin, respectively. When adjusting using a continuous propensity score, linezolid had an HR of 0.78 (95% CI 0.48-1.27) for CLABSI duration, an OR of 0.23 (95% CI 0.02-2.56) for early recurrence and an OR of 0.9 (95% CI 0.3-2.67) for mortality, relative to vancomycin. Conclusions: There was no statistically significant difference between linezolid and vancomycin when used as definitive treatment for hVICoNS CLABSI in NICU patients, in terms of CLABSI duration, recurrence or all-cause mortality.


Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Linezolid/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus/efectos de los fármacos , Vancomicina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Bacteriemia/microbiología , Coagulasa/deficiencia , Estudios de Cohortes , Femenino , Mortalidad Hospitalaria , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Linezolid/administración & dosificación , Linezolid/sangre , Masculino , Estudios Retrospectivos , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/mortalidad , Staphylococcus/clasificación , Staphylococcus/enzimología , Staphylococcus/aislamiento & purificación , Resultado del Tratamiento , Vancomicina/administración & dosificación , Vancomicina/sangre , Vancomicina/farmacología
18.
J Int Neuropsychol Soc ; 23(3): 266-286, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28069095

RESUMEN

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the central nervous system, representing the primary cause of non-traumatic disability in young adults. Cognitive dysfunction can affect patients at any time during the disease process and might alter the six core functional domains. Social cognition is a multi-component construct that includes the theory of mind, empathy and social perception of emotions from facial, bodily and vocal cues. Deficits in this cognitive faculty might have a drastic impact on interpersonal relationships and quality of life (QoL). Although exhaustive data exist for non-social cognitive functions in MS, only a little attention has been paid for social cognition. The objectives of the present work are to reappraise the definition and anatomy of social cognition and evaluate the integrity of this domain across MS studies. We will put special emphasis on neuropsychological and neuroimaging studies concerning social cognitive performance in MS. METHODS: Studies were selected in conformity with PRISMA guidelines. We looked for computerized databases (PubMed, Medline, and Scopus) that index peer-reviewed journals to identify published reports in English and French languages that mention social cognition and multiple sclerosis, regardless of publication year. We combined keywords as follows: (facial emotion or facial expression or emotional facial expressions or theory of mind or social cognition or empathy or affective prosody) AND multiple sclerosis AND (MRI or functional MRI or positron emission tomography or functional imaging or structural imaging). We also scanned references from articles aiming to get additional relevant studies. RESULTS: In total, 26 studies matched the abovementioned criteria (26 neuropsychological studies including five neuroimaging studies). Available data support the presence of social cognitive deficits even at early stages of MS. The increase in disease burden along with the "multiple disconnection syndrome" resulting from gray and white matters pathology might exceed the "threshold for cerebral tolerance" and can manifest as deficits in social cognition. Admitting the impact of the latter on patients' social functioning, a thorough screening for such deficits is crucial to improving patients' QoL. (JINS, 2017, 23, 266-286).


Asunto(s)
Trastornos del Conocimiento/etiología , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/psicología , Conducta Social , Trastornos del Conocimiento/diagnóstico por imagen , Bases de Datos Bibliográficas/estadística & datos numéricos , Humanos , Esclerosis Múltiple/diagnóstico por imagen , Calidad de Vida/psicología
20.
Eur Neurol ; 77(5-6): 316-321, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28467982

RESUMEN

BACKGROUND/AIMS: Phosphorus magnetic resonance spectroscopy (31P-MRS) has previously shown abnormal changes in energy metabolites in the brain of multiple sclerosis (MS) patients. However, the relationship between these energy metabolites - particularly adenosine triphosphate (ATP) - and the disease severity remains unclear. The objective of this study was to determine whether measuring ATP metabolites can help to predict disease severity in MS patients. METHODS: 31P-MRS at 3 tesla was performed in 9 relapsing remitting (RRMS), 9 secondary progressive MS patients (SPMS), and 10 age-matched healthy controls. ATP metabolites (expressed as %) in normally appearing white matter of the centrum semiovale were compared between patients and healthy controls. The relationship between Expanded Disability Status Scale (EDSS) and ATP metabolites was evaluated. RESULTS: RRMS and SPMS patients had higher phosphocreatine (PCr) and lower phosphodiesters than healthy controls. In addition, RRMS patients had higher ß-ATP% than SPMS patients. ß-ATP% was negatively correlated with EDSS in all patients. CONCLUSION: Our findings suggest a defective PCr metabolism in both patient groups, and a higher state of energy production in RRMS that might reflect a compensatory mechanism in face of the increased needs. The correlation of ß-ATP with EDSS makes it a candidate biomarker for assessing MS disease severity.


Asunto(s)
Adenosina Trifosfato/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Esclerosis Múltiple/metabolismo , Adulto , Encéfalo/metabolismo , Encéfalo/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/patología , Sustancia Blanca/metabolismo , Sustancia Blanca/patología
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