Transplantation of dorsal root ganglia overexpressing the NaChBac sodium channel improves locomotion after complete SCI.

Spinal cord injury (SCI) is a debilitating condition currently lacking treatment. Severe SCI causes the loss of most supraspinal inputs and neuronal activity caudal to the injury, which, coupled with the limited endogenous capacity for spontaneous regeneration, can lead to complete functional loss even in anatomically incomplete lesions. We hypothesized that transplantation of mature dorsal root ganglia (DRGs) genetically modified to express the NaChBac sodium channel could serve as a therapeutic option for functionally complete SCI. We found that NaChBac expression increased the intrinsic excitability of DRG neurons and promoted cell survival and neurotrophic factor secretion in vitro. Transplantation of NaChBac-expressing dissociated DRGs improved voluntary locomotion 7 weeks after injury compared to control groups. Animals transplanted with NaChBac-expressing DRGs also possessed higher tubulin-positive neuronal fiber and myelin preservation, although serotonergic descending fibers remained unaffected. We observed early preservation of the corticospinal tract 14 days after injury and transplantation, which was lost 7 weeks after injury. Nevertheless, transplantation of NaChBac-expressing DRGs increased the neuronal excitatory input by an increased number of VGLUT2 contacts immediately caudal to the injury. Our work suggests that the transplantation of NaChBac-expressing dissociated DRGs can rescue significant motor function, retaining an excitatory neuronal relay activity immediately caudal to injury.

Cleaning technologies integrated in duct flows for the inactivation of pathogenic microorganisms in indoor environments: A critical review of recent innovations and future challenges.

Pathogenic microorganisms are a major concern in indoor environments, particularly in sensitive facilities such as hospitals, due to their potential to cause nosocomial infections. This study evaluates the concentration of airborne bacteria and fungi in the University Hospital Complex of Albacete (Spain), comparing the results with recent literature. Staphylococcus is identified as the most prevalent bacterial genus with a percentage distribution of 35%, while Aspergillus represents the dominant fungal genus at 34%. The lack of high Technology Readiness Levels (TRL 6, TRL 7) for effective indoor air purification requires research efforts to bridge this knowledge gap. A screening of disinfection technologies for pathogenic airborne microorganisms such as bacteria and fungi is conducted. The integration of filtration, irradiation or and (electro)chemical gas treatment systems in duct flows is discussed to enhance the design of the air-conditioning systems for indoor air purification. Concerns over microbial growth have led to recent studies on coating commercial fibrous air filters with antimicrobial particles (silver nanoparticles, iron oxide nanowires) and polymeric materials (polyaniline, polyvinylidene fluoride). Promising alternatives to traditional short-wave UV-C energy for disinfection include LED and Far-UVC irradiation systems. Additionally, research explores the use of TiO2 and TiO2 doped with metals (Ag, Cu, Pt) in filters with photocatalytic properties, enabling the utilization of visible or solar light. Hybrid photocatalysis, combining TiO2 with polymers, carbon nanomaterials, or MXene nanomaterials, enhances the photocatalytic process. Chemical treatment systems such as aerosolization of biocidal agents (benzalkonium chloride, hydrogen peroxide, chlorine dioxide or ozone) with their possible combination with other technologies such as adsorption, filtration or photocatalysis, are also tested for gas disinfection. However, the limited number of studies on the use of electrochemical technology poses a challenge for further investigation into gas-phase oxidant generation, without the formation of harmful by-products, to raise its TRL for effectively inactivating airborne microorganisms in indoor environments.

ThermoTRP channels in pain sexual dimorphism: new insights for drug intervention.

Chronic pain is a major burden for the society and remains more prevalent and severe in females. The presence of chronic pain is linked to persistent alterations in the peripheral and the central nervous system. One of the main types of peripheral pain transducers are the transient receptor potential channels (TRP), also known as thermoTRP channels, which intervene in the perception of hot and cold external stimuli. These channels, and especially TRPV1, TRPA1 and TRPM8, have been subjected to profound investigation because of their role as thermosensors and also because of their implication in acute and chronic pain. Surprisingly, their sensitivity to endogenous signaling has been far less studied. Cumulative evidence suggests that the function of these channels may be differently modulated in males and females, in part through sexual hormones, and this could constitute a significant contributor to the sex differences in chronic pain. Here, we review the exciting advances in thermoTRP pharmacology for males and females in two paradigmatic types of chronic pain with a strong peripheral component: chronic migraine and chemotherapy-induced peripheral neuropathy (CIPN). The possibilities of peripheral druggability offered by these channels and the differential exploitation for men and women represent a development opportunity that will lead to a significant increment of the armamentarium of analgesic medicines for personalized chronic pain treatment.

Paclitaxel in vitro reversibly sensitizes the excitability of IB4(-) and IB4(+) sensory neurons from male and female rats.

BACKGROUND AND PURPOSE: Paclitaxel produces a chemotherapy-induced peripheral neuropathy that persists in 50-60% of cancer patients upon treatment. Evidence from animal models suggests an axonopathy of peripheral A- and C-type fibres that affects their excitability. However, direct effects of paclitaxel on sensory neuron excitability and sexual dimorphism remain poorly understood. EXPERIMENTAL APPROACH: We used a long-lasting (10 days in vitro) primary culture of rat dorsal root ganglion (DRG) neurons to investigate the time course effect of paclitaxel on the electrical activity of IB4(-) and IB4(+) sensory neurons of female and male adult Wistar rats. KEY RESULTS: Paclitaxel strongly and reversibly stimulated spontaneous activity and augmented action potential tonic firing in IB4(-) and IB4(+) neurons in both sexes, peaking at 48 h post-treatment and virtually disappearing at 96 h. Paclitaxel decreased the current rheobase for action potential firing by reducing and accelerating the after-hyperpolarization phase. Molecularly, paclitaxel modulated Na+ and K+ ion currents. Particularly, the drug significantly augmented the function of Nav 1.8, TRPV1 and TRPM8 channels. Furthermore, paclitaxel increased Nav 1.8 and TRPV1 expression at 48 h post-treatment. Notably, we observed that female DRG neurons appear more sensitive to paclitaxel sensitization than their male counterparts. CONCLUSIONS AND IMPLICATIONS: Our data indicate that paclitaxel similarly potentiated IB4(-) and IB4(+) electrogenicity and uncover a potential sex dimorphism in paclitaxel-induced chemotherapy-induced peripheral neuropathy. Our in vitro, pre-clinical, chemotherapy-induced peripheral neuropathy paradigm provides a tool for studying the dynamics and underlying molecular mechanisms contributing to nociceptor sensitization in peripheral neuropathies and for testing desensitizing compounds.

Disinfection of polymicrobial urines by electrochemical oxidation: Removal of antibiotic-resistant bacteria and genes.

In this work, data obtained from the University Hospital Complex of Albacete (Spain) were selected as a case study to carry out the disinfection experiments. To do this, different configurations of electrochemical reactors were tested for the disinfection of complex urines. Results showed that 4-6 logs bacterial removal were achieved for every bacterium tested when working with a microfluidic flow-through reactor after 180 min (0.423 Ah dm-3). The MIKROZON® cell reached a total disinfection after 60 min (1.212 Ah dm-3), causing severe damages induced in the cell walls observed in SEM images. The concentration profiles of the electrogenerated disinfectants in solution could explain the differences observed. Additionally, a mean decrease in the ARGs concentration ranked as follows: blaKPC (4.18-logs) > blaTEM (3.96-logs) > ermB (3.23-logs) using the MIKROZON® cell. This electro-ozonizer could be considered as a suitable alternative to reduce the risk of antibiotic resistance spread. Hence, this study provides an insight into different electrochemical reactors for the disinfection of complex hospital urine matrices and contributes to reduce the spread of antibiotic resistance through the elimination of ARGs. A topic of great importance nowadays that needs to be further studied.

Factores asociados a bajo rendimiento cognitivo en adultos con sospecha de apnea obstructiva del sueño / Factors associated with low cognitive performance in adults with suspected obstructive sleep apnea

La apnea obstructiva del sueño (AOS) se ha asociado a deterioro cognitivo. OBJETIVO: Identificar factores asociados a bajo rendimiento cognitivo (BRC) en adultos con sospecha de AOS. MÉTODO: Se realizó evaluación cognitiva empleando la Evaluación Cognitiva de Montreal (MoCA); se consideró BRC un puntaje inferior a 21. El diagnóstico de AOS fue mediante poligrafía respiratoria de 5 canales, según índice de apnea-hipopnea (IAH). Se evaluó también calidad de sueño, síntomas depresivos, entre otros. RESULTADOS: En 91,5% de 320 pacientes consecutivos se confirmó el diagnóstico de AOS. El promedio de MoCA fue 20,6 puntos. El grupo con BRC tenía mayor edad, menor escolaridad; mayor frecuencia de hipertensión arterial y diabetes mellitus, y desaturaciones de la oxihemoglobina de mayor magnitud. No hubo diferencias de gravedad según IAH entre ambos grupos. COMENTARIO: Los pacientes con BRC presentan factores de riesgo asociados a deterioro cognitivo, y mayor magnitud de desaturaciones de la oxihemoglobina.

Obstructive sleep apnea (OSA) has been associated with cognitive decline. OBJECTIVE: To identify factors associated with low cognitive performance (LCP) in adults with suspected OSA. MATHOD: Cognitive evaluation was performed using Montreal Cognitive Assessment (MoCA), and scores lower than 21 were considered LCP. The diagnosis of OSA was made using 5-channel respiratory polygraphy, according to the apnea-hypopnea index (AHI). Sleep quality, depressive symptoms, among others, were also evaluated. RESULTS: In 91.5% of 320 consecutive patients the diagnosis of OSA was confirmed. The MoCA average was 20.6 points. The group with LCP was older, less educated, were more likely to have hypertension and diabetes mellitus, and with more severe oxyhemoblobin desaturations. There were no differences in severity according to AHI between both groups. COMMENT: Patients with LCP have risk factors associated with cognitive impairment, besides more severe oxyhemoglobin desaturations.

A review on disinfection technologies for controlling the antibiotic resistance spread.

The occurrence of antibiotic-resistant bacteria (ARB) in water bodies poses a sanitary and environmental risk. These ARB and other mobile genetic elements can be easily spread from hospital facilities, the point in which, for sure, they are more concentrated. For this reason, novel clean and efficient technologies are being developed for allowing to remove these ARB and other mobile genetic elements before their uncontrolled spread. In this paper, a review on the recent knowledge about the state of the art of the main disinfection technologies to control the antibiotic resistance spread from natural water, wastewater, and hospital wastewater (including urine matrices) is reported. These technologies involve not only conventional processes, but also the recent advances on advanced oxidation processes (AOPs), including electrochemical advanced oxidation processes (EAOPs). This review summarizes the state of the art on the applicability of these technologies and also focuses on the description of the disinfection mechanisms by each technology, highlighting the promising impact of EAOPs on the remediation of this important environmental and health problem.

[Reversible neurotoxicity secondary to metronidazole: report of one case]. / Neurotoxicidad secundaria a metronidazol: un efecto adverso reversible. Caso clínico.

Metronidazole can cause adverse effects both in the central and peripheral nervous system. We report a 34-year-old female who presented a reversible cerebellar syndrome and peripheral neuropathy as an adverse effect associated with the use of metronidazole. Brain magnetic resonance imaging (MRI) showed hyperintense T2 and FLAIR bilateral symmetrical cerebellar lesions, without contrast enhancement or mass effect, isointense in diffusion-weighted imaging and hypointense in apparent diffusion coefficient sequences. Also, electrophysiological evaluation was consistent with axonal polyneuropathy. She had received metronidazole for a liver abscess during 49 days. After discontinuation of metronidazole, she had rapid regression of cerebellar symptoms and normalization of MRI, with subsequent disappearance of peripheral symptoms. The brain MRI, electromyography and nerve conduction studies performed at 35 months later showed complete resolution of the lesions. Although metronidazole neurotoxicity is a rare event, it must be borne in mind because the prognosis is usually favorable after stopping the drug.

Neurotoxicidad secundaria a metronidazol: un efecto adverso reversible. Caso clínico / Reversible neurotoxicity secondary to metronidazole report of one case

Metronidazole can cause adverse effects both in the central and peripheral nervous system. We report a 34-year-old female who presented a reversible cerebellar syndrome and peripheral neuropathy as an adverse effect associated with the use of metronidazole. Brain magnetic resonance imaging (MRI) showed hyperintense T2 and FLAIR bilateral symmetrical cerebellar lesions, without contrast enhancement or mass effect, isointense in diffusion-weighted imaging and hypointense in apparent diffusion coefficient sequences. Also, electrophysiological evaluation was consistent with axonal polyneuropathy. She had received metronidazole for a liver abscess during 49 days. After discontinuation of metronidazole, she had rapid regression of cerebellar symptoms and normalization of MRI, with subsequent disappearance of peripheral symptoms. The brain MRI, electromyography and nerve conduction studies performed at 35 months later showed complete resolution of the lesions. Although metronidazole neurotoxicity is a rare event, it must be borne in mind because the prognosis is usually favorable after stopping the drug.

[Seroepidemiology of Coxiella burnetii infection among blood donors in Albacete]. / Seroepidemiología de la infección por Coxiella burnetii en donantes de sangre en Albacete.

INTRODUCTION: The objectives of this study were to determine the prevalence of antibodies to Coxiella burnetii among blood donors and to examine the epidemiological characteristics of C. burnetii infection in Albacete, Spain. METHODS: A total of 863 serum samples were collected from blood donors aged 18-65 years. Donor samples were stratified by age, sex, and residence (rural or urban). IgG and IgM titers to the C. burnetii phase II antigen were determined by an indirect immunofluorescence assay. RESULTS: The prevalence of anti-phase II IgG was 23.1%, and three (0.3%) donors had positive IgM titers. Men were more frequently seropositive than women (29% vs. 18%; OR: 1.85; 95% CI: 1.34-2.56), and this difference was not related to differential occupational exposure to animals. Pet ownership had no impact on seroprevalence. In contrast, occupations involving contact with domestic ungulates were associated with a higher seroprevalence (OR: 2.39; 95% CI: 1.04-5.48). Nevertheless, 90% of seropositive donors reported no contact with farm animals. CONCLUSION: Our results show that C. burnetii infection is highly endemic in Albacete and that most infections are not linked to specific occupational exposure in this area. The high prevalence of antibodies to C. burnetii among blood donors indicates the advisability of studies to determine the risk of transfusion-transmitted Q fever in endemic areas.