Lysosome-related organelles contain an expansion compartment that mediates delivery of zinc transporters to promote homeostasis.

Zinc is an essential nutrient-it is stored during periods of excess to promote detoxification and released during periods of deficiency to sustain function. Lysosome-related organelles (LROs) are an evolutionarily conserved site of zinc storage, but mechanisms that control the directional zinc flow necessary for homeostasis are not well understood. In Caenorhabditis elegans intestinal cells, the CDF-2 transporter stores zinc in LROs during excess. Here, we identify ZIPT-2.3 as the transporter that releases zinc during deficiency; ZIPT-2.3 transports zinc, localizes to the membrane of LROs in intestinal cells, and is necessary for zinc release from LROs and survival during zinc deficiency. In zinc excess and deficiency, the expression levels of CDF-2 and ZIPT-2.3 are reciprocally regulated at the level of mRNA and protein, establishing a fundamental mechanism for directional flow to promote homeostasis. To elucidate how the ratio of CDF-2 and ZIPT-2.3 is altered, we used super-resolution microscopy to demonstrate that LROs are composed of a spherical acidified compartment and a hemispherical expansion compartment. The expansion compartment increases in volume during zinc excess and deficiency. These results identify the expansion compartment as an unexpected structural feature of LROs that facilitates rapid transitions in the composition of zinc transporters to mediate homeostasis, likely minimizing the disturbance to the acidified compartment.

AlInAsSb Geiger-mode SWIR and eSWIR SPADs with high avalanche probability.

Single-photon avalanche diodes (SPADs) that are sensitive to photons in the Short-wave infrared and extended short-wave infrared (SWIR and eSWIR) spectra are important components for communication, ranging, and low-light level imaging. The high gain, low excess noise factor, and widely tunable bandgap of AlxIn1-xAsySb1-y avalanche photodiodes (APDs) make them a suitable candidate for these applications. In this work, we report single-photon-counting results for a separate absorption, charge, and multiplication (SACM) Geiger-mode SPAD within a gated-quenching circuit. The single-photon avalanche probabilities surpass 80% at 80 K, corresponding with single-photon detection efficiencies of 33% and 12% at 1.55 µm and 2 µm, respectively.

Dentate nucleus: a review and implications for dentatotomy.

PURPOSE: The dentate nucleus (DN) is the largest, most lateral, and phylogenetically most recent of the deep cerebellar nuclei. Its pivotal role encompasses the planning, initiation, and modification of voluntary movement but also spans non-motor functions like executive functioning, visuospatial processing, and linguistic abilities. This review aims to offer a comprehensive description of the DN, detailing its embryology, anatomy, physiology, and clinical relevance, alongside an analysis of dentatotomy. METHODS AND RESULTS: We delve into the history, embryology, anatomy, vascular supply, imaging characteristics, and clinical significance of the DN. Furthermore, we thoroughly review the dentatotomy, emphasizing its role in treating spasticity. CONCLUSIONS: Understanding the intricacies of the anatomy, physiology, vasculature, and projections of the DN has taken on increased importance in current neurosurgical practice. Advances in technology have unveiled previously unknown functions of the deep cerebellar nuclei, predominantly related to non-motor domains. Such discoveries are revitalizing older techniques, like dentatotomy, and applying them to newer, more localized targets.

Genetic polymorphisms rs1800871 and rs1800872 of IL-10 gene are associated with dengue infection, especially with serotype 1 and DwoWS in Mexican population.

INTRODUCTION: Dengue infection is generated by a complex interaction between DENV (Dengue Virus) and the host's immune response. Interleukin-10 is an immunoregulatory cytokine during DENV infection. The objective of this study was to investigate whether genetic variants in IL-10 could be useful as a predictive and susceptibility marker in the prognosis of DENV infection, particularly with serotype 1, and in participants with dengue without warning signs. MATERIAL AND METHODS: A study of cases (n = 365) and controls (n = 364) was carried out. Genotyping was performed by real-time PCR using TaqMan probes. Sample size power was calculated using Quanto software RESULTS: This is the first report showing the independent association of the T allele of rs1800871 (P = 0.023) and the A allele of rs1800872 (P = 0.010) with the risk of dengue infection. Statistical analysis established the genotypic association of IL-10 SNPs with DENV infection under different inheritance models. Our results also showed the association of the CC, TC, and CA haplotypes (P = 0.0064, P = 0.0032, and P = 0.0010 respectively) with infection. Furthermore, both polymorphic sites were associated with the risk of DwoWS and serotype 1 (Den-1) under different inheritance models. Finally, under the dominant model, we identified a positive correlation between IL-10 levels vs. IFN-γ and IL-8. CONCLUSION: Our results show the first independent association of the T and A alleles of the polymorphic sites rs1800871 and rs1800872, with dengue infection, particularly with Den-1, and in participants with DwoWs.

Counting the Capital's cats: Estimating drivers of abundance of free-roaming cats with a novel hierarchical model.

Free-roaming cats are a conservation concern in many areas but identifying their impacts and developing mitigation strategies requires a robust understanding of their distribution and density patterns. Urban and residential areas may be especially relevant in this process because free-roaming cats are abundant in these anthropogenic landscapes. Here, we estimate the occupancy and density of free-roaming cats in Washington D.C. and relate these metrics to known landscape and social factors. We conducted an extended camera trap survey of public and private spaces across D.C. and analyzed data collected from 1483 camera deployments from 2018 to 2020. We estimated citywide cat distribution by fitting hierarchical occupancy models and further estimated cat abundance using a novel random thinning spatial capture-recapture model that allows for the use of photos that can and cannot be identified to individual. Within this model, we utilized individual covariates that provided identity exclusions between photos of unidentifiable cats with inconsistent coat patterns, thus increasing the precision of abundance estimates. This combined model also allowed for unbiased estimation of density when animals cannot be identified to individual at the same rate as for free-roaming cats whose identifiability depended on their coat characteristics. Cat occupancy and abundance declined with increasing distance from residential areas, an effect that was more pronounced in wealthier neighborhoods. There was noteworthy absence of cats detected in larger public spaces and forests. Realized densities ranged from 0.02 to 1.75 cats/ha in sampled areas, resulting in a district-wide estimate of ~7296 free-roaming cats. Ninety percent of cat detections lacked collars and nearly 35% of known individuals were ear-tipped, indicative of district Trap-Neuter-Return (TNR) programs. These results suggest that we mainly sampled and estimated the unowned cat subpopulation, such that indoor/outdoor housecats were not well represented. The precise estimation of cat population densities is difficult due to the varied behavior of subpopulations within free-roaming cat populations (housecats, stray and feral cats), but our methods provide a first step in establishing citywide baselines to inform data-driven management plans for free-roaming cats in urban environments.

Usability and perceptions of a one-on-one telementoring program for young physicians in rural settings of Peru: a mixed method study.

BACKGROUND: Telementoring seems to be a promising strategy to deliver training and counselling to physicians in remote areas. In Peru, early graduated physicians must work for the Rural and Urban-Edge Health Service Program where they face important training needs. The aim of this study was to describe the usage of a one-on-one telementoring program for rural physicians and evaluate the aspects related to the perceptions of acceptability and usability. METHODS: Mixed methods study on recently graduated physicians who work in rural areas and participate in the telementoring program. The program used a mobile application to connect these young doctors with specialized mentors to answer queries about real-life problems raised by working in a rural area. We summarize administrative data to assess participant characteristics and their participation in the program. Additionally, we conducted in-depth interviews to explore the perceived usability, ease of use, and reason for non-use of the telementoring program. RESULTS: Of 74 physicians (mean age 25, 51.4% women) enrolled, 12 (16.2%) actively used the program and performed a total of 27 queries, which received response in an average time of 5.4 ± 6.3 h. In the interviews, the main reasons for non-use were connectivity issues, feelings of shame, and self-efficacy. For those who used the telementoring program they referred it was easy to use and solve their inquiries timely. CONCLUSIONS: The implementation of a telementoring program sought to provide guidance to recently graduated physicians working in rural areas. Low use rates show that administrative and process-related deficiencies in the program implementation need to be improved.

Microsurgical and illustrative anatomy of the cavernous sinus, middle fossa, and paraclival triangles: a straightforward, comprehensive review.

The middle fossa, cavernous sinus, and paraclival triangles consist of ten triangles. Their use in a surgical approach is vast; most are used as landmarks to access and identify other structures of surgical interest. Multiple labels, borders, and contents mentioned by different authors make understanding and reproduction challenging and confusing. This study aims to organize and clarify recent or most relevant publications and disclose our portrayal of the ten triangles using cadaveric dissection and simple and practical figures. Four middle fossa triangles, four cavernous sinus triangles, and two paraclival triangles were dissected and delineated in a cadaveric specimen. Drawings were simplified to eliminate confusion and evaluate the triangles effortlessly. Similarities and differences in triangle names, border limits, and contents are described in a precise form. The recognition of triangle landmarks allows for treating pathologies in a frequently distorted anatomy or challenging to access structure. That is why an accurate knowledge of the surgical anatomy should be mastered, and a safe approach should be accomplished.

On the effects of diabetes mellitus on the mechanical properties of DRG sensory neurons and their possible relation with diabetic neuropathy.

Diabetic neuropathy (DN) is one of the principal complications of diabetes mellitus (DM). Dorsal root ganglion (DRG) neurons are the primary sensory neurons that transduce mechanical, chemical, thermal, and pain stimuli. Diabetes-caused sensitivity alterations and presence of pain are due to cellular damage originated by persistent hyperglycemia, microvascular insufficiency, and oxidative and nitrosative stress. However, the underlying mechanisms have not been fully clarified. The present work addresses this problem by hypothesizing that sensitivity changes in DN result from mechanotransduction-system alterations in sensory neurons; especially, plasma membrane affectations. This hypothesis is tackled by means of elastic-deformation experiments performed on DGR neurons from a murine model for type-1 DM, as well a mathematical model of the cell mechanical structure. The obtained results suggest that the plasma-membrane fluidity of DRG sensory neurons is modified by the induction of DM, and that this alteration may correlate with changes in the cell calcium transient that results from mechanical stimuli.

Comparative analysis of bacterial content, levels of lipopolysaccharides and lipoteichoic acid in symptomatic and asymptomatic endodontic infections at different stages of endodontic treatment.

OBJECTIVES: This study aimed to detect the presence of specific bacteria and to evaluate the levels of lipopolysaccharides (LPS) and lipoteichoic acid (LTA) in symptomatic necrotic root canals associated with acute apical abscess (symptomatic group - GI). It also aimed to compare the findings with those presented by asymptomatic necrotic root canals (asymptomatic group - GII) in the different stages of the endodontic treatment. MATERIALS AND METHODS: Microbiological samples were collected from 20 root canals, including purulent collection from acute apical abscesses, before and after chemo-mechanical preparation (CMP) preparation (CMP) with chlorhexidine gel 2% and after 30 days of intracanal medication (ICM) with (Ca[OH]2) + chlorhexidine. The culture method was used to evaluate the efficacy of CMP and ICM. Nested PCR was used to detect the presence of 17 specific bacteria. Levels of LPS were measured by using limulus amebocyte lysate, whereas enzyme-linked immunosorbent assay was used for the quantification of LTA. RESULTS: CMP was effective in reducing the microbial load in both groups (P < 0.05). LPS levels were higher in GI than in GII (P < 0.05). There was a significant reduction in the LPS levels after CMP and ICM (P < 0.05) in GI and GII. LTA levels were significantly reduced in GI after ICM and in GII after CMP and ICM (both P < 0.05). Fusobacterium nucleatum and Enterococcus faecalis were frequently identified in both groups, alone or in combination with each other. CONCLUSION: Different species were detected in all stages of the endodontic treatment. CMP was able to reduce bacterial content and the levels of LPS, but not of LTA in the symptomatic group. High levels of LPS were correlated with spontaneous pain and pain to percussion in the symptomatic group. CLINICAL RELEVANCE: This clinical study showed that chemo-mechanical preparation was able to reduce bacterial load and levels of LPS, but not of LTA in the symptomatic group. Elevated levels of LPS were correlated with the presence of symptomatology.

Has the COVID-19 Pandemic Impacted Interest in Cosmetic Facial Plastic Surgery? A Google Trends Analysis.

Facial cosmetic surgery trends are evolving in the current climate of the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to evaluate public interest in elective facial plastic surgery during the COVID-19 pandemic including the period of the COVID-19 vaccine distribution using Google Trends. A Google Trends analysis was completed using popular terms related to facial cosmetic surgery and procedures from March 2017 to August 2021. Three stages were identified (baseline, pre-COVID-19 vaccine distribution, and post-COVID-19 vaccine distribution). Descriptive statistics were calculated and two-tailed t-tests were performed between the pre-vaccine and the post-vaccine phases. Linear regression analysis was also performed to determine percent deflection of search terms. There was significantly greater interest in facial aesthetic procedure search terms, except for tear trough filler, during the post-COVID-19 vaccine phase compared with the pre-COVID-19 vaccine phase. There was greater interest in lower facial procedure interest during this phase compared with upper facial procedures (p-value = 0.0011). The search terms with the greatest deflection percentage during the post-vaccine phase were lip filler, brow lift, and lip flip. There continues to be high demands of facial plastic surgery and procedures despite COVID-19 pandemic.

Comparison of Photoscreening to Chart Methodology for Vision Screening.

The goal of this study is to assess the referral rate accuracy of photoscreening versus the chart methodology in identifying preschool children at risk of amblyopia and amblyogenic refractive error. Vision screenings using the plusoptiX S12 and the LEA chart were performed on 127 children, aged 3-5 years old. Comprehensive eye exams were performed after screenings. The sensitivity and specificity of the plusoptiX S12 were 80.3% and 92.1% and the LEA chart were 43.6% and 94.8%, respectively. The sensitivity of the plusoptiX S12 is significantly higher than the LEA (p value: <.001). After eye exams, 82.9% were correctly passed by the plusoptiX S12 and 64% were correctly passed by the LEA chart (p value: .009). Objective photoscreening is significantly more accurate in identifying preschool children at risk of developing amblyopia and should be considered best practice. The chart methodology provides an inaccurate report on a preschool child's amblyopic risk.

Noisy stimulation effect in calcium dynamics on cardiac cells.

Noise is present in nature, and it affects the nervous and cardiovascular system. Noise added to stimuli may change the performance of excitable cells. In this paper, we study the effect of noise on the two main heart cell types: pacemaker and myocardial cells. This study investigates whether noise can induce changes in calcium dynamics on the two main heart cell types: pacemaker and myocardial cells, when stimuli with periodic electrical signals are disturbed by Gaussian white noise. Calcium dynamic parameters were obtained using imaging signals. Our results show that low intensities of noise favor amplitude and raise rate calcium dynamics, although our results show that the pacemaker cells are not affected by a noisy stimulus. Altogether, these findings suggest that noise plays a key role in calcium dynamics.

Detection of Streptococcus mutans in symptomatic and asymptomatic infected root canals.

OBJECTIVES: To investigate the presence of Streptococcus mutans in root canals of symptomatic necrotic teeth (SNT) and their associated acute apical abscesses (AAA) and in the root canals of asymptomatic necrotic teeth (ANT). It also aimed to investigate the presence of the cnm and cbm genes in specimens that harbored S. mutans. MATERIALS AND METHODS: DNA was extracted from samples collected from 10 patients presenting pulpal necrosis associated with radiographic evidence of apical periodontitis (ANT) and from 10 patients in need of endodontic therapy due to the presence of pulpal necrosis (SNT) and AAA. The control group consisted of 10 patients with teeth with normal vital pulp and requiring endodontic treatment for prosthetic reasons. The presence of S. mutans was detected by quantitative real-time-PCR (qPCR) using species-specific primers. Samples harboring S. mutans were further evaluated for the presence of CBP genes by qPCR as well. RESULTS: All studied sites showed a high prevalence of S. mutans, except the control group. Specifically, 60% of ANT and 70% of AAA/SNT paired samples were positive for S. mutans. The cnm gene was detected positive for S. mutans only in ANT samples (66.6%). The cbm gene was not detected in any of the investigated sites. CONCLUSIONS: S. mutans was found in high prevalence in both asymptomatic and symptomatic endodontic infections, including in abscesses, but it was not detected in the root canals of teeth with normal vital pulp. Interestingly, cnm+ S. mutans was only detected in asymptomatic/chronic primary endodontic infections associated with apical lesion. Therefore, it appears that cnm, and possibly other CBPs, may play an underestimated role in chronic endodontic infections. CLINICAL RELEVANCE: A high prevalence of Streptococcus mutans cnm+ gene was detected only in asymptomatic primary endodontic infections associated with apical lesion. Therefore, it appears that this collagen-binding protein gene plays an underestimated role in asymptomatic/chronic endodontic infections.

COVID-19 epidemiology in a Mexican tertiary care hospital.

INTRODUCTION: As a result of COVID-19, many hospitals underwent a conversion for the care for this disease. OBJECTIVE: To analyze COVID-19 hospital epidemiological behavior from March to August 2020. METHODS: Through a series of cases, COVID-19 epidemiological behavior at the hospital was analyzed, for which simple case rates, percentages and incidence of COVID-19 per 100 hospital discharges were estimated. RESULTS: Out of 491 subjects who tested positive for SARS-CoV-2, 156 (31.7 %) were hospitalized for clinical data of moderate to severe disease. Average age was 59.1 years; 121 cases (75 %) were discharged due to improvement, and 32 (20.5 %), due to death. Average age of those who died was 69.7 years, and the most affected age group was 60 to 80 years (45.4 %). Calculated lethality was 20.5 per 100 hospital discharges, while that calculated taking into account positive patients (outpatients and hospitalized patients) was 6.5. CONCLUSIONS: COVID-19 epidemiological behavior was similar to that described in other studies; however, lethality and mortality are above national average. The analysis of this and of the factors that favored it in our population is pending.

INTRODUCCIÓN: A consecuencia de COVID-19, numerosos hospitales sufrieron una reconversión para la atención de esta enfermedad. OBJETIVO: Analizar el comportamiento epidemiológico hospitalario de COVID-19 entre marzo y agosto de 2020. MÉTODOS: En una serie de casos se analizó el comportamiento epidemiológico de COVID-19 en un hospital de tercer nivel, para lo cual se estimaron frecuencias simples de casos, porcentajes e incidencia por cada 100 egresos hospitalarios. RESULTADOS: De 491 sujetos con prueba positiva para SARS-CoV-2, 156 (31.7 %) fueron hospitalizados por datos clínicos de enfermedad moderada a grave. La edad promedio fue de 59.1 años; 121 casos (75 %) egresaron por mejoría y 32 (20.5 %), por defunción. El promedio de edad de quienes fallecieron fue de 69.7 años y el grupo etario más afectado fue el de 60 a 80 años (45.4 %). La letalidad calculada fue de 20.5 por 100 egresos hospitalarios, mientras que la calculada tomando en cuenta los pacientes positivos (ambulatorios y hospitalizados) fue de 6.5. CONCLUSIONES: El comportamiento epidemiológico de COVID-19 fue similar al descrito en otros estudios; sin embargo, la letalidad y la mortalidad están por encima de la media nacional. Está pendiente el análisis de estas y de los factores que las favorecieron en nuestra población.

Efficacy and safety of dabrafenib-trametinib in the treatment of unresectable or metastatic melanoma with BRAF V600 mutation: A systematic review and network meta-analysis.

The current systematic review aimed to evaluate the efficacy and safety of dabrafenib plus trametinib (dabrafenib-trametinib) with those of other therapeutic alternatives in the treatment of patients with BRAF V600 mutation unresectable or metastatic melanoma. The search was carried out on four databases up to July-2018. Two separate network meta-analyses (NMA) were performed using the frequentist method (random effects): one with an exclusive population with BRAF V600 mutation (NMA-pBRAFV600) and another with a mixed population (with or without the mutation: NMA-pMixed). An evidence profile was included using the GRADE method for NMA. The validity of the final estimator in the NMA-pMixed was assessed via sensitivity analysis. Five clinical trials were included in the NMA-pBRAFV600. In the NMA-pBRAFV600 population, dabrafenib-trametinib had a favorable effect on overall survival (OS) and progression-free survival (PFS) compared with dabrafenib, vemurafenib, and dacarbazine, and on partial response rate (PRR) and overall response rate (ORR) compared with dacarbazine and vemurafenib. In the NMA-pMixed population, dabrafenib-trametinib had a positive effect on OS vs ipilimumab 3 mg/kg and on PFS and PRR vs ipilimumab (3 and 10 mg/kg), nivolumab, and pembrolizumab. However, dabrafenib-trametinib, and vemurafenib-cobimetinib were comparable in terms of clinical efficacy. In addition, dabrafenib-trametinib was associated with less grades 3 and 4 adverse events.

Efficacy and safety of dabrafenib-trametinib in the treatment of unresectable advanced/metastatic melanoma with BRAF-V600 mutation: A systematic review and network meta-analysis.

The current systematic review aimed to evaluate and compare the efficacy and safety of dabrafenib-trametinib with those of other therapeutic alternatives in the treatment of patients with unresectable advanced/metastatic melanoma with BRAF-V600 mutation. The search was carried out on four databases up to July 2018. Two separate network meta-analyses (NMA) were performed using the frequentist method (random effects): one with an exclusive population with BRAF-V600 mutation (NMA-pBRAFV600) and another with mixed population (with or without the mutation: NMA-pMixed). An evidence profile was included using the GRADE method for NMA. The validity of the final estimator in the NMA-pMixed was assessed via a sensitivity analysis. Nine clinical trials were included in the NMA-pBRAFV600. Dabrafenib-trametinib was found to have a favorable effect on overall survival (OS) and progression-free survival (PFS) compared with dabrafenib, vemurafenib, and dacarbazine and on partial response rate (PRR) and overall response rate compared with dacarbazine and vemurafenib. In the NMA-pMixed, dabrafenib-trametinib was found to have a positive effect on OS versus ipilimumab 3 mg/kg and on PFS and PRR versus ipilimumab, nivolumab, and pembrolizumab. However, dabrafenib-trametinib and vemurafenib-cobimetinib significantly differed in terms of efficacy. In addition, dabrafenib-trametinib has a favorable effect on Grades 3 and 4 adverse events.

Mechanically-Induced Long-Period Fiber Gratings Using Laminated Plates.

This work presents a formation method of mechanically-induced long-period fiber gratings using laminated plates. The mechanically-induced long-period fiber grating is temporarily inscribed by compressing the optical fiber between a flat plate and the proposed laminated plate. In turn, the new laminated plate consists of a parallel assembling of single-edged utility blades. We present the experimental characterization of mechanically-induced long-period fiber gratings while employing three laminated plates with a period of 480 ± 20 µm and low duty cycles. These mechanically-induced long-period fiber gratings display a leading rejection band (>15 dB) with a couple of shallow rejection bands (<2 dB) in the range of 1100-1700 nm. This spectral behavior is due to the new mechanical fabrication process that is based on laminated plates that we have proposed, which consists of piling multiple blades with trapezoidal edges that are polished with different levels to obtain different duty-cycles. With the proposed method, we can obtain values of duty-cycles around 10%, much lower than those obtained using traditional methods. Additionally, with this new method, the required mechanical pressure to form the grating is remarkably reduced, which minimizes the probability of the optical fiber failure in the mechanically-induced long-period fiber gratings (MI-LPFGs). Moreover, the proposed mechanically-induced long-period fiber gratings with a single rejection band open the feasibility to implement coarse wavelength division multiplexing systems that are based on long-period fiber gratings.

Scleral surgical repair through the use of nanostructured fibrin/agarose-based films in rabbits.

Scleral defects can result as a consequence of trauma, infectious diseases or cancer and surgical repair with allogeneic scleral grafts can be required. However, this method has limitations and novel alternatives are needed. Here, the efficacy of acellular nanostructured fibrin-agarose hydrogel-based substitutes (NFAH) in the repair of scleral defects in rabbits was studied. For this, scleral defects of 5-mm diameter were made on 18 adult-male New Zealand rabbits and repaired with acellular NFAH, NFAH crosslinked with genipin (NFAH-GP) or glutaraldehyde (NFAH-GA), allogeneic scleral grafts as control (C-CTR) or not repaired (negative control N-CTR) (n = 3 each). Macroscopic and histological analyses were performed after 40-days. Macroscopy confirmed the repair of all defects in a comparable manner than the C-CTR. Histology showed no degradation nor integration in C-CTR while NFAH-GP and NFAH-GA biomaterials were encapsulated by connective and inflammatory tissues with partial biodegradation. The NFAH were fully biodegraded and replaced by a loose connective tissue and sclera covering the defects. This in vivo study demonstrated that the NFAH are a promising biocompatible and pro-regenerative alternative to the use of allogeneic cadaveric grafts. However, large defects and long-term studies are needed to demonstrate the potential clinical usefulness of these substitutes.

Mechanosensitive ion channel inhibitors promote the stiffening of the plasma membrane of mouse sensory neurons.

The mechanosensitivity of cells depends on the lipid-protein interactions of the plasma membrane. Affectations in the lipid region of the plasma membrane affect the transduction of mechanical forces, and any molecule that modifies the biophysical integrity of the lipid bilayer can alter the mechanical activity of the proteins inside the membrane. To understand whether inhibitors of mechanically activated ion channels affect the mechanical properties of the plasma membrane, we evaluated the rigidity of the membrane of sensory neurons of the DRG of mice using a variant of the scanning ion conductance microscopy method, which allows us to calculate the Young's modulus of individual cells before and after the perfusion of different doses of Gd3+, ruthenium red and GsMTx-4. Our results suggest that these molecules compromise the membrane by increasing the Young's modulus value, which indicates that the membrane becomes more rigid; these compounds act through different mechanisms and by a non-specific manner, each one shows a certain preference for specific cell subpopulations, depending on their cell size and their reactivity to isolectin B4. Our results support the idea that the biophysical properties that result from the interactions that arise in the membranes are part of the mechanotransduction process.

Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV).

OBJECTIVE: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. DESIGN: International, multicenter, prospective, randomized controlled clinical trial. SETTING: A network of university hospitals. PARTICIPANTS: The study comprises 1,380 patients scheduled for thoracic surgery. INTERVENTIONS: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. MEASUREMENTS AND MAIN RESULTS: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients.