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Introduction: Previous studies have reported a correlation between a high-grade CMV-infection and an unfavorable prognosis in glioblastoma (GB). Coversely, epilepsy has been associated with a more favorable outcome in GB patients. Despites epilepsy and CMV share similar molecular mechanisms in GB tumoral microenvironment, the correlation between Tumor-Related-Epilepsy (TRE) and CMVinfection remains unexplored. The aim of our study is to examine the correlation between the dregree of CMV infection and seizure types on the survival of TRE Adult-type-diffuse-glioma. To achieve this objective, we conducted a comprehensive literature review to assess our results regarding previous publications. Methods: We conducted a retrospective-observational study on TRE Adult-type-diffuse-gliomas treated at a single center in Mexico from 2010 to 2018. Tumor tissue and cDNA were analyzed by immunochemistry (IHC) for CMV (IE and LA antigens) at the Karolinska Institute in Sweden, and RT-PCR for CMV-gB in Torreon Mexico, respectively. Bivariate analysis (X2-test) was performed to evaluate the association between subtypes of Adult-type-diffuse-glioma (IDH-mut grade 4 astrocytoma vs. IDH-wt glioblastoma) and the following variables: type of hemispheric involvement (mesial vs. neocortical involvement), degree of CMV infection (<25%vs. >25% infected-tumoral cells) and seizure types [Focal awareness, focal impaired awareness, and FBTCS]. Kaplan Meier and Cox analyses were performed to determine the risk, p < 0.05 was considered statistically significant. Results: Sixty patients with TRE Adult type diffuse gliomas were included (80% IDH-wt glioblastoma and 20% IDH-mut grade 4astrocytomas). The mean age was 61.5 SD ± 18.4, and 57% were male. Fifty percent of the patients presented with mesial involvement of the hemysphere. Seizure types included focal awareness (15%), focal impaired awareness (43.3%), and FBTCS (41.7%). Ninety percent of cases were treated with Levetiracetam and 33.3% presented Engel-IA postoperative seizure control. More than 90% of samples were positive for CMV-immunohistochemistry (IHC). However, all cDNA analyzed by RT-PCR return negative results. The median of overall survival (OS) was 15 months. High-grade CMV-IE infection (14 vs. 25 months, p<0.001), mesial involvement (12 vs. 18 months, p<0.001), and FBTCS were associated with worse OS (9 vs.18 months for non-FBTCS). Multivariate analysis demonstrated that high-grade CMV infection (HR = 3.689, p=0.002) and FBTCS (HR=7.007, p<0.001) were independent unfavorable survival factors. Conclusions: CMV induces a proinflammatory tumoral microenvironment that contributes to the developmet of epilepsy. Tumor progression could be associated not only with a higher degree of CMV infection but also to epileptogenesis, resulting in a seizure phenotype chracterized by FBTCS and poor survival outcomes. This study represents the first survival analysis in Latin America to include a representative sample of TRE Adult-type diffuse gliomas considering CMV-infection-degree and distinguishing features (such as FBTCS) that might have potential clinical relevance in this group of patients. Further prospective studies are required to validate these results.

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BACKGROUND: Current scientific evidence has pointed out the relevance of hemostatic products for improving clinical outcomes in liver trauma, including increased survival rates and reductions in bleeding-related complications. The purpose of this study was to compare the use of the gelatin-thrombin flowable (Flowable) versus the standard technique of Packing in a new experimental liver injury model. METHODS: Twenty-four swine were prospectively randomized to receive either Flowable or standard packing technique. We used a novel severe liver injury model, in which the middle and left suprahepatic veins were selectively injured, causing an exsanguinating hemorrhage. The main outcome measure was the percentage of lost blood volume. RESULTS: The median total percentage of total blood volume per animal lost, from injury to minute 120, was significantly lower in the Flowable group (15.2%; interquartile range: 10.7-46.7%) than in the Packing group (64.9%; Interquartile range: 53.4-73.0%) (Hodges-Lehmann median difference: 41.1%; 95% CI: 18.9-58.0%, p = 0.0034). The 24-hour survival rate was significantly higher in the Flowable group (87.0%) than in the Packing group (0.0%) (Hazard ratio (HR) 0.08; 95% confidence interval 0.102 to 0.27; p < 0.0001). Mean-arterial pressure was significantly lower at minute 60 and 120 in the Flowable group than in the packing group (p = 0.0258 and p = 0.0272, respectively). At minute 120, hematocrit was higher in the Flowable than in the packing group (Hodges-Lehmann median difference: 5.5%; 95%CI: 1.0 to11.0, p = 0.0267). Finally, the overall-surgical-procedure was significantly shorter with Flowable than with Packing (Hodges-Lehmann median difference: 39.5 s, 95% CI: 25.0 to 54.0 s, p = 0.0004). CONCLUSIONS: The use of the Flowable was more effective in achieving hemostasis, reducing blood loss, and improving survival rates than standard packing in a severe porcine-liver bleeding model.

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PURPOSE: Coccidioidal meningitis (CM) is an uncommon disease frequently misdiagnosed. Neuroimaging and mortality are not considered in detail in previous pediatric CM series. Our objective is to evaluate outcome of pediatric neurococcidiomycosis in relation to neuroimaging findings. METHODS: We performed a prospective, observational, cross-sectional study in children with hydrocephalus and CM treated at Specialties Hospital in Torreon, Mexico (between 2015 and 2020). The outcome was evaluated by Hydrocephalus Outcome Questionnaire (HOQ) and the modified Rankin Scale (mRS). Follow-up was established at the first shunt surgery and survival since CM diagnosis confirmation. Neuroimaging was analyzed in relation to clinical data, outcome and survival. Kaplan-Meier analysis was performed with IBM-SPSS-25. RESULTS: Ten pediatric cases with CM and hydrocephalus were reported. Aged 6-228 months, 60% were female. Mean number of surgeries was 4.3 SD ± 3 (range 1-15). Asymmetric hydrocephalus was the most common neuroimaging finding (70%), followed by cerebral vasculitis (20%) and isolated fourth ventricle (IFV) (20%). The mean HOQ overall score was 0.338 SD ± 0.35. A minimum follow-up of 18 months was reported. Mean survival was 13.9 SD ± 6.15 months (range 3-24). Poor survival was correlated with asymmetric hydrocephalus (p = 0.335), cerebral vasculitis (p = 0.176), IFV (p < 0.001), bacterial superinfection (p = 0.017), lower mRS scores at hospital discharge (p = 0.017) and during follow-up (p = 0.004). The mortality rate was 20%. CONCLUSIONS: We report the largest series in Latin America of pediatric CM and hydrocephalus. Asymmetric hydrocephalus, IFV and cerebral vasculitis are complications that increase mortality and must be early diagnosed for a timely surgical and medical treatment. HOQ and mRS could be alternative scales to evaluate outcome in these patients. After a long follow-up (18 months), survival remained poor after diagnosis confirmation in our series.

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Some hepatic wound models have been developed in pigs with the aim of reproducing liver injury; however, the wound shape, severity, and outcome differ among them. The novel injury profile employed in this study differed from that used elsewhere for standardized, repeatable, reproducible, incising-penetrating, vascular, and severe injury in swine. It is made with a cutting object that penetrates deep into the hepatic parenchyma, always affecting the two suprahepatic veins at the point where they merge into the common trunk. The primary outcome was reproducibility and replicability of the surgical method. The secondary outcome was the analysis of some variables (blood loss, survival, and flow) to validate the model. •This novel method of liver injury provides a liver injury with the following characteristics: standardized, incise-penetrated, deep, bloody, and severe.•This model can be used for research (trauma, hepato-bilio-pancreatic, pharmaceutical) and training (damage control surgery).•Method name: Incising-Penetrating, Vascular and Severe Liver Injury Model in Swine.

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The antimicrobial properties of photocatalysts have long been studied. However, most of the available literature describes their antibacterial properties, while knowledge of their antiviral activity is rather scarce. Since the outset of the coronavirus disease 2019 (COVID-19) pandemic, an increasing body of research has suggested their antiviral potential and highlighted the need for further research in this area. In this study, we investigated the virucidal properties of a commercial TiO2-coated photocatalytic glass against a model human coronavirus. Our findings demonstrate that the TiO2-coated glass consistently inactivates coronaviruses upon contact under daylight illumination, in a time-dependent manner. A 99% drop in virus titer was achieved after 3.9 h. The electron micrographs of virus-covered TiO2-glass showed a reduced number of virions compared to control glass. Morphological alterations of TiO2-exposed viruses included deformation, disruption of the viral envelope, and virion ghosts, endorsing the application of this material in the construction of protective elements to mitigate the transmission of viruses. To the best of our knowledge, this is the first report showing direct visual evidence of human coronaviruses being damaged and morphologically altered following exposure to this photocatalyst. IMPORTANCE Surface contamination is an important contributor to SARS-CoV-2 spread. The use of personal protective elements and physical barriers (i.e., masks, gloves, and indoor glass separators) increases safety and has proven invaluable in preventing contagion. Redesigning these barriers so that the virus cannot remain infectious on them could make a difference in COVID-19 epidemiology. The introduction of additives with virucidal activity could potentiate the protective effects of these barriers to serve not only as physical containment but also as virus killers, reducing surface contamination after hand touch or aerosol deposition. We performed in-depth analysis of the kinetics of photocatalysis-triggered coronavirus inactivation on building glass coated with TiO2. This is the first report showing direct visual evidence (electron microscopy) of coronaviruses being morphologically damaged following exposure to this photocatalyst, demonstrating the high potential of this material to be incorporated into daily-life high-touch surfaces, giving them an added value in decelerating the virus spread.

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Focused shock waves have emerged as a highly effective noninvasive therapeutic option for the treatment of calcific tendinitis of the shoulder. There are three types of focused shock wave generators: electrohydraulic, electromagnetic, and piezoelectric. According to our literature search, there are no reports of results with the use of single-crystal piezoelectric generators in calcific tendinitis of the shoulder. In a consecutive retrospective series of 23 patients with Gärtner type I and II calcifications of the rotator cuff, we performed three applications of high-energy piezoelectric focused waves (4,000 pulses per session with a frequency of 6 Hz). At the final follow-up (average of 14 months), 82.6% of the cases showed complete resorption of the calcification in radiographic controls. In 8.7% of the cases, partial disappearance of the calcification was achieved, and in the remaining 8.7% there were no significant changes. Single-crystal piezoelectric generators have a success rate comparable to those already reported with electrohydraulic and electromagnetic devices.

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BACKGROUND: Discrimination, abuse, and mistreatment are prevailing problems reported in neurosurgical training programs globally. Moreover, the current coronavirus disease 2019 (COVID-19) pandemic may also show a negative impact on burnout levels in neurosurgery residents. This study aims to evaluate burnout, discrimination, and mistreatment in neurosurgical residents training in Latin America during the severe acute respiratory syndrome coronavirus 2 era. METHODS: A 33-item electronic survey was sent to neurosurgery residents from Latin America from May 10 to 25, 2021. Statistical analysis was performed using SPSS version 25. RESULTS: A total of 111 neurosurgery residents responded to the survey. Mean age was 29.39 ± 2.37 years; 22.5% were female and 36% were training in Mexico. Residents who reported experiencing discrimination for testing positive to COVID-19 had the highest levels of depersonalization (66.7%; P = 0.043) and emotional exhaustion (75%; P = 0.023). Female respondents reported higher rates of gender discrimination (80% vs. 1.2%; P = 0.001), abuse (84% vs. 58.1%; P < 0.005), and sexual harassment (24% vs. 0%; P < 0.001) than did male respondents. Residents training in Mexico reported lower rates of emotional or verbal abuse (59.2% vs. 32.5%; P = 0.007) and bullying (P < 0.005) than did those in other countries in Latin America. Older age was a protective factor for high depersonalization scores (odds ratio [OR], 0.133; 95% confidence interval [CI], 0.035-0.500). Experiencing discrimination represented a risk factor for presenting high emotional exhaustion scores (OR, 3.019; 95% CI, 1.057-8.629). High levels of depersonalization were associated with a 7-fold increased risk of suicidal ideation (OR, 7.869; 95% CI, 1.266-48.88). CONCLUSIONS: The COVID-19 pandemic has been a significant burden on several aspects of health care workers' lives. Our results provide a broad overview of its impact on burnout, discrimination, and mistreatment as experienced by neurosurgery residents training in Latin America, laying the groundwork for future studies and potential interventions.

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Recent advances in memristive nanocrystal assemblies leverage controllable colloidal chemistry to induce a broad range of defect-mediated electrochemical reactions, switching phenomena, and modulate active parameters. The sample geometry of virtually all resistive switching studies involves thin film layers comprising monomodal diameter nanocrystals. Here we explore the evolution of bipolar and threshold resistive switching across highly ordered, solution-processed nanoribbon assemblies and mixtures comprising BaZrO3 (BZO) and SrZrO3 (SZO) nanocrystals. The effects of nanocrystal size, packing density, and A-site substitution on operating voltage (VSET and VTH) and switching mechanism were studied through a systematic comparison of nanoribbon heterogeneity (i.e., BZO-BZO vs BZO-SZO) and monomodal vs bimodal size distributions (i.e., small-small and small-large). Analysis of the current-voltage response confirms that tip-induced, trap-mediated space-charge-limited current and trap-assisted tunneling processes drive the low- and high-resistance states, respectively. Our results demonstrate that both smaller nanocrystals and heavier alkaline earth substitution decrease the onset voltage and improve stability and state retention of monomodal assemblies and bimodal nanocrystal mixtures, thus providing a base correlation that informs fabrication of solution-processed, memristive nanocrystal assemblies.

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Nanocrystals (NCs) are complex systems that offer a superior level of detailed engineering at the atomic level. The large number of novel and revolutionary applications have made nanocrystals of special interest. In particular oxide perovskites are one of the most widely investigated family of materials in solid-state chemistry, especially for their ferroelectric and superconducting properties. In addition to these well-known properties, perovskites show good electrical conductivity (close to metals), ion conductivity and mixed ionic-electronic conductivity. In that sense, controlled synthesis of nanomaterials with special care over size and shape are essential in many fields of science and technology. Although it is well-known that physical methods deliver excellent quality nanomaterials, their high production cost has increased the interest to more affordable alternative chemical processes. In this review, we focus on the preparation of sub-10 nm oxide perovskite nanocrystals and the main strategies used to control the final properties of the obtained products. In the second part, we present the methods available for nanocrystal solutions processing together with the most remarkable applications foreseen.

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BACKGROUND: Coccidioidal meningitis (CM) is a fungal infectious disease that rarely affects children. Even in endemic areas, coccidiomycosis rarely affects the pediatric population. However, 40% of affected children develop hydrocephalus. Here, we describe the clinical, serological, and neuroimaging findings in a series of Mexican children admitted to our neurosurgical service with hydrocephalus and subsequently diagnosed with CM. METHODS: We report a prospective series of pediatric patients with hydrocephalus secondary to CM in an endemic area at the north of Mexico. Our report includes children with CM who were hospitalized from 2015 to 2019 in a regional hospital in Torreón, Coahuila. Clinical evolution was monitored for 1 year after hospital discharge. RESULTS: Our series include five children with CM (2-17-years-old, three female), who were hospitalized for hydrocephalus and developed intracranial hypertension. The most frequent neuroimaging findings were leptomeningeal enhancement (5/5) and basal arachnoiditis (4/5), followed by asymmetric hydrocephalus (3/5), abnormalities in fourth ventricle morphology (3/5), and cerebral vasculitis (2/5). CM was diagnosed by positive serology or pathology studies. All children were initially managed with fluconazole and a shunt was placed for management of hydrocephalus. Four patients recovered without permanent neurological deficits and one subject developed persistent vegetative state. One year after hospital discharge, none of the subjects died. CONCLUSION: This series contributes to the limited number of pediatric CM cases reported in the literature, and describes neuroimaging findings in the pediatric population. The cases here presented show that the identification of Coccidioides as causal agent in pediatric meningitis is crucial for targeted treatment and can affect dramatically neurological prognosis. Furthermore, our report stresses that even in endemic areas pediatric coccidiomycosis represents a diagnostic challenge, which is further exacerbated by the limited availability of resources in these regions. Therefore, a positive immunoglobulin G by enzyme immunoassay is enough for diagnosis of CM in endemic areas without access to CF.

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BACKGROUND: Recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents an important negative impact on global training of neurosurgery residents. Even before the pandemic, discrimination is a challenge that neurosurgical residents have consistently faced. In the present study, we evaluated discriminatory conditions experienced by residents during their neurosurgical training in Mexico before the SARS-CoV-2 pandemic. METHODS: An electronic survey of 18 questions was sent among residents registered in the Mexican Society of Neurological Surgery (MSNS), between October 2019 and July 2020. Statistical analysis was made in IBM SPSS Statistics 25. The survey focused on demographic characteristics, discrimination, personal satisfaction, and expectations of residents. RESULTS: A response rate of 50% (132 of 264 residents' members of MSNS) was obtained and considered for analysis. Median age was 30.06 ± 2.48 years, 5.3% (n = 7) were female and 16.7% (n = 22) were foreigners undergoing neurosurgical training in Mexico. Approximately 27% of respondents suffered any form of discrimination, mainly by place of origin (9.1%), by gender (8.3%) or by physical appearance (6.1%). About 42.9% (n = 3) of female residents were discriminated by gender versus 6.4% (n = 8) of male residents (P = 0.001); while foreign residents mentioned having suffered 10 times more an event of discrimination by place of origin compared to native Mexican residents (36.4% vs. 3.6%, P < 0.001). CONCLUSION: This manuscript represents the first approximation to determine the impact of discrimination suffered by residents undergoing neurosurgical training in Mexico before the SARS-CoV-2 pandemic.

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EAG (ether-à-go-go or KCNH) are a subfamily of the voltage-gated potassium (Kv) channels. Like for all potassium channels, opening of EAG channels drives the membrane potential toward its equilibrium value for potassium, thus setting the resting potential and repolarizing action potentials. As voltage-dependent channels, they switch between open and closed conformations (gating) when changes in membrane potential are sensed by a voltage sensing domain (VSD) which is functionally coupled to a pore domain (PD) containing the permeation pathway, the potassium selectivity filter, and the channel gate. All Kv channels are tetrameric, with four VSDs formed by the S1-S4 transmembrane segments of each subunit, surrounding a central PD with the four S5-S6 sections arranged in a square-shaped structure. Structural information, mutagenesis, and functional experiments, indicated that in "classical/Shaker-type" Kv channels voltage-triggered VSD reorganizations are transmitted to PD gating via the α-helical S4-S5 sequence that links both modules. Importantly, these Shaker-type channels share a domain-swapped VSD/PD organization, with each VSD contacting the PD of the adjacent subunit. In this case, the S4-S5 linker, acting as a rigid mechanical lever (electromechanical lever coupling), would lead to channel gate opening at the cytoplasmic S6 helices bundle. However, new functional data with EAG channels split between the VSD and PD modules indicate that, in some Kv channels, alternative VSD/PD coupling mechanisms do exist. Noticeably, recent elucidation of the architecture of some EAG channels, and other relatives, showed that their VSDs are non-domain swapped. Despite similarities in primary sequence and predicted structural organization for all EAG channels, they show marked kinetic differences whose molecular basis is not completely understood. Thus, while a common general architecture may establish the gating system used by the EAG channels and the physicochemical coupling of voltage sensing to gating, subtle changes in that common structure, and/or allosteric influences of protein domains relatively distant from the central gating machinery, can crucially influence the gating process. We consider here the latest advances on these issues provided by the elucidation of eag1 and erg1 three-dimensional structures, and by both classical and more recent functional studies with different members of the EAG subfamily.

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Voltage-dependent potassium channels (Kv channels) are crucial regulators of cell excitability that participate in a range of physiological and pathophysiological processes. These channels are molecular machines that display a mechanism (known as gating) for opening and closing a gate located in a pore domain (PD). In Kv channels, this mechanism is triggered and controlled by changes in the magnitude of the transmembrane voltage sensed by a voltage-sensing domain (VSD). In this review, we consider several aspects of the VSD⁻PD coupling in Kv channels, and in some relatives, that share a common general structure characterized by a single square-shaped ion conduction pore in the center, surrounded by four VSDs located at the periphery. We compile some recent advances in the knowledge of their architecture, based in cryo-electron microscopy (cryo-EM) data for high-resolution determination of their structure, plus some new functional data obtained with channel variants in which the covalent continuity between the VSD and PD modules has been interrupted. These advances and new data bring about some reconsiderations about the use of exclusively a classical electromechanical lever model of VSD⁻PD coupling by some Kv channels, and open a view of the Kv-type channels as allosteric machines in which gating may be dynamically influenced by some long-range interactional/allosteric mechanisms.

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Recent cryo-EM data have provided a view of the KCNH potassium channels molecular structures. However, some details about the cytoplasmic domains organization and specially their rearrangements associated to channel functionality are still lacking. Here we used the voltage-dependent dipicrylamine (DPA)-induced quench of fluorescent proteins (FPS) linked to different positions at the cytoplasmic domains of KCNH2 (hERG) to gain some insights about the coarse structure of these channel parts. Fast voltage-clamp fluorometry with HEK293 cells expressing membrane-anchored FPs under conditions in which only the plasma membrane potential is modified, demonstrated DPA voltage-dependent translocation and subsequent FRET-triggered FP quenching. Our data demonstrate for the first time that the distance between an amino-terminal FP tag and the intracellular plasma membrane surface is shorter than that between the membrane and a C-terminally-located tag. The distances varied when the FPs were attached to other positions along the channel cytoplasmic domains. In some cases, we also detected slower fluorometric responses following the fast voltage-dependent dye translocation, indicating subsequent label movements orthogonal to the plasma membrane. This finding suggests the existence of additional conformational rearrangements in the hERG cytoplasmic domains, although their association with specific aspects of channel operation remains to be established.

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INTRODUCCIÓN: En la actualidad existen pocas escalas validadas para valorar la bronquiolitis aguda (BA) y escasa información de su potencia de prueba. El objetivo del presente estudio es valorar la validez de una escala de severidad de BA (ESBA) para orientar los ingresos en UCIP. Pacientes y método: Estudio observacional prospectivo descriptivo de lactantes previamente sanos menores de un año con BA, donde se utilizó la ESBA para contrastar la gravedad con la necesidad de ingreso en UCIP. El tamaño de la muestra se estimó en al menos 175 pacientes. El equipo investigador fue entrenado en el uso de la ESBA. Todos los pacientes del estudio fueron evaluados con la ESBA diariamente y en caso de deterioro clínico. Se analizaron y compararon las puntuaciones ESBA inicial y máxima respecto a la necesidad de UCIP. Se construyó una curva operativa de receptor, se calculó el área bajo la curva y se estimó el punto óptimo de sensibilidad/especificidad. RESULTADOS: Se incluyó a 190 pacientes (varón/mujer: 58%/42%). Precisaron UCIP 11 (6%). La puntuación media± DE de la ESBA-máxima para pacientes que precisaron y no precisaron UCIP fue de 10,55 ± 1,12 y 6,35 ± 2,3, respectivamente. Esta diferencia fue significativa (p < 0,001). El ABC para la ESBA-máxima fue 0,94 (p < 0,001; IC del 95%: 0,90-0,98). El punto de corte óptimo se estableció en ≥ 10 puntos, para una sensibilidad del 82% y una especificidad del 91%. CONCLUSIONES: La ESBA estima la gravedad de la BA respecto a la necesidad e ingreso en UCIP con una sensibilidad y especificidad de utilidad clínica

INTRODUCTION: At present, there are few validated scoring tests for assessing acute bronchiolitis (AB) severity, and limited information on their test power. The aim of the present study is to evaluate the validity of an acute bronchiolitis severity score (ABSS) to help in deciding PICU admission. PATIENTS AND METHOD: Prospective, descriptive, observational study of previously healthy infants under 1 year of age with AB, where the ABSS was used to compare severity as regards the need for PICU admission. The sample size was estimated as at least 175 patients. The research team was trained in the use of ABSS. All patients in the study were evaluated with ABSS daily, as well as in the case of clinical deterioration. The initial and maximum ABSS scores were contrasted to the need for PICU admission. A receiver operative curve was constructed, and the area under the curve was calculated, and the optimum point of sensitivity / specificity was estimated. RESULTS: The study included a total of 190 patients (male / female: 58% / 42%). PICU was required in 11 (6%). The mean± SD ABSS-maximal score for patients who required and did not require PICU was 10.55 ± 1.12 and 6.35 ± 2.3, respectively (P<.001). The AUC for ABSS-maximal was 0.94 (P<.001, 95% CI: 0.90-0.98). The optimal cut-off point was set at ≥10 points for a sensitivity of 82% and a specificity of 91%. CONCLUSIONS: ABSS estimates the severity of AB regarding the need for PICU admission, with a sensitivity and specificity of clinical usefulness

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Voltage-dependent KCNH family potassium channel functionality can be reconstructed using non-covalently linked voltage-sensing domain (VSD) and pore modules (split channels). However, the necessity of a covalent continuity for channel function has not been evaluated at other points within the two functionally independent channel modules. We find here that by cutting Kv11.1 (hERG, KCNH2) channels at the different loops linking the transmembrane spans of the channel core, not only channels split at the S4-S5 linker level, but also those split at the intracellular S2-S3 and the extracellular S3-S4 loops, yield fully functional channel proteins. Our data indicate that albeit less markedly, channels split after residue 482 in the S2-S3 linker resemble the uncoupled gating phenotype of those split at the C-terminal end of the VSD S4 transmembrane segment. Channels split after residues 514 and 518 in the S3-S4 linker show gating characteristics similar to those of the continuous wild-type channel. However, breaking the covalent link at this level strongly accelerates the voltage-dependent accessibility of a membrane impermeable methanethiosulfonate reagent to an engineered cysteine at the N-terminal region of the S4 transmembrane helix. Thus, besides that of the S4-S5 linker, structural integrity of the intracellular S2-S3 linker seems to constitute an important factor for proper transduction of VSD rearrangements to opening and closing the cytoplasmic gate. Furthermore, our data suggest that the short and probably rigid characteristics of the extracellular S3-S4 linker are not an essential component of the Kv11.1 voltage sensing machinery.

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RESUMEN Se presenta el caso de gestante de 26 años de edad, afecta del síndrome Klippel Trenaunay Weber congénito, con su primer embarazo el cual concluyó a las 39 semanas, mediante cesárea, obteniéndose recién nacido de 3450 gramos, buen Apgar al nacer, con evolución satisfactoria para el binomio madre-hijo. Se revisó bibliografía universal sobre esta patología, resaltándose los riesgos potenciales para la madre y su producto. Aún cuando la frecuencia de aparición de esta entidad es rara, resulta importante su conocimiento para los profesionales que laboran, tanto en la atención primaria de salud, como en la atención secundaria (AU).

ABSTRACT The case of a 26-years-old woman is presented. She presented the Klippel-Trenaunay-Weber syndrome in her first pregnancy finished at the 39th week through caesarian section; the newborn was 3450 grams, with good Apgar at birth: the mother-child binomial had a satisfactory evolution. The universal bibliography on this disease was reviewed, highlighting the potential risk for mother and child. Even when the frequency of this entity is rare, it is important its knowledge for the professionals working in the primary health care as much as in the secondary health care (AU).

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RESUMEN Se presenta el caso de gestante de 26 años de edad, afecta del síndrome Klippel Trenaunay Weber congénito, con su primer embarazo el cual concluyó a las 39 semanas, mediante cesárea, obteniéndose recién nacido de 3450 gramos, buen Apgar al nacer, con evolución satisfactoria para el binomio madre-hijo. Se revisó bibliografía universal sobre esta patología, resaltándose los riesgos potenciales para la madre y su producto. Aún cuando la frecuencia de aparición de esta entidad es rara, resulta importante su conocimiento para los profesionales que laboran, tanto en la atención primaria de salud, como en la atención secundaria (AU).

ABSTRACT The case of a 26-years-old woman is presented. She presented the Klippel-Trenaunay-Weber syndrome in her first pregnancy finished at the 39th week through caesarian section; the newborn was 3450 grams, with good Apgar at birth: the mother-child binomial had a satisfactory evolution. The universal bibliography on this disease was reviewed, highlighting the potential risk for mother and child. Even when the frequency of this entity is rare, it is important its knowledge for the professionals working in the primary health care as much as in the secondary health care. (AU)

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