Evidence of combined flower thermal and drought vulnerabilities portends reproductive failure under hotter-drought conditions.

Despite the abundant evidence of impairments to plant performance and survival under hotter-drought conditions, little is known about the vulnerability of reproductive organs to climate extremes. Here, by conducting a comparative analysis between flowers and leaves, we investigated how variations in key morphophysiological traits related to carbon and water economics can explain the differential vulnerabilities to heat and drought among these functionally diverse organs. Due to their lower construction costs, despite having a higher water storage capacity, flowers were more prone to turgor loss (higher turgor loss point; ΨTLP) than leaves, thus evidencing a trade-off between carbon investment and drought tolerance in reproductive organs. Importantly, the higher ΨTLP of flowers also resulted in narrow turgor safety margins (TSM). Moreover, compared to leaves, the cuticle of flowers had an overall higher thermal vulnerability, which also resulted in low leakage safety margins (LSM). As a result, the combination of low TSMs and LSMs may have negative impacts on reproduction success since they strongly influenced the time to turgor loss under simulated hotter-drought conditions. Overall, our results improve the knowledge of unexplored aspects of flower structure and function and highlight likely threats to successful plant reproduction in a warmer and drier world.

Pandemic policies and sleeping problems in older adults.

Sleep quality is fundamental to physical and mental health. Recent research shows that the COVID-19 pandemic has affected individuals' sleep quality. This study aims to investigate whether the containment and health policies (Oxford Coronavirus Government Response Tracker indexes) adopted by European countries and Israel during the pandemic are related to sleep problems in people aged 50 and over. A cross-sectional study was conducted using a logistic regression analysis based on data from the Survey of Health, Ageing and Retirement in Europe, collected in 27 European countries and Israel, in 2021. The results show that containment and health policies affect older adults' sleep, once we neutralise the influence of the sociodemographic, economic, and health characteristics of the individuals and close contact with COVID-19. In fact, the more containment and health policies, the fewer chances of sleep problems. A possible explanation for this is that these policies give people over 50 a sense of safety and security in relation to COVID-19, which may reduce sleep problems.

Anti-inflammatory actions of aspirin-triggered resolvin D1 (AT-RvD1) in bronchial epithelial cells stimulated by cigarette smoke extract.

Smoking causes several diseases such as chronic obstructive pulmonary disease (COPD). Aspirin-triggered-resolvin D1 (AT-RvD1) is a lipid mediator produced during the resolution of inflammation and demonstrates anti-inflammatory and pro-resolution effects in several inflammatory experimental models including in the airways. Here we evaluated the role of AT-RvD1 (100 nM) in bronchial epithelial cells (BEAS-2B) stimulated by cigarette smoke extract (CSE; 1%; 1 cigarette) for 24 h. CSE induced the productions of IL-1ß, TNF-α, IL-10, IL-4 and IFN-γ as well as the activations of NF-κB and STAT3 and the expression of ALX/FPR2 receptor. AT-RvD1 reduced the IL-1ß and TNF-α production and increased the production of IFN-γ. These effects were reversed BOC2, an antagonist of ALX/FPR2 receptor for AT-RvD1. The production of IL-4 and IL-10 were not altered by AT-RvD1. In addition, AT-RvD1 reduced the phosphorylation of NF-κB and STAT3 when compared to CSE-stimulated BEAS-2B cells. No alteration of ALX/FPR2 expression was observed by AT-RvD1 when compared to CSE group. In the human monocytic leukemia cell line, the relative number of copies of IL-1ß and IL-4 was significantly higher in CSE + AT-RvD1 group compared CSE group, however, the expression of M1 cytokine was more pronounced than M2 profile. AT-RvD1 could be an important target for the reduction of inflammation in the airways associated with smoking.

Assessment of the association of myofibroblasts and structural components of the extracellular matrix with histopathological parameters of actinic cheilitis and lower lip squamous cell carcinoma.

BACKGROUND: To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs). METHODS: Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-ß, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05). RESULTS: ACs showed higher number of α-SMA+ MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-ß (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA+ MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA+ cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047). CONCLUSIONS: Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.

Hippocampal Microglia Activation Induced by Acute Pancreatic Injury in Rats.

BACKGROUND: Acute pancreatitis is an inflammation of the pancreatic glandular parenchyma that causes injury with or without the destruction of pancreatic acini. Clinical and experimental evidence suggest that certain systemic proinflammatory mediators may be responsible for initiating the fundamental mechanisms involved in microglial reactivity. Here, we investigated the possible repercussions of acute pancreatitis (AP) on the production of inflammatory mediators in the brain parenchyma focusing on microglial activation in the hippocampus. METHODS: The acute pancreatic injury in rats was induced by a pancreas ligation surgical procedure (PLSP) on the splenic lobe, which corresponds to approximately 10% of total mass of the pancreas. Blood samples were collected via intracardiac puncture for the measurement of serum amylase. After euthanasia, frozen or paraffin-embedded brains and pancreas were analyzed using qRT-PCR or immunohistochemistry, respectively. RESULTS: Immunohistochemistry assays showed a large number of Iba1 and PU.1-positive cells in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus of the PLSP group. TNF-α mRNA expression was significantly higher in the brain from PLSP group. NLRP3 inflammasome expression was found to be significantly increased in the pancreas and brain of rats of the PLSP group. High levels of BNDF mRNA were found in the rat brain of PLSP group. In contrast, NGF mRNA levels were significantly higher in the control group versus PLSP group. CONCLUSION: Our findings suggest that AP has the potential to induce morphological changes in microglia consistent with an activated phenotype.

Muscle Strength of Lower Limbs as a Postoperative Predictor in Bariatric Surgery.

OBJECTIVE: The aim of our study was to assess postoperative lower limbs muscle strength (MS) as a predictor of late surgical success (36 months). METHODS: Body composition analyses and isokinetic dynamometry evaluation were performed before (T0: n=123), six months (T1: n=123) and 36 months (T2: n=79) after Roux-en-y gastric bypass (RYGB). Surgical success (SS) was defined as ≥ 50% excess weight loss (EWL) 36 months after surgery or ≤ 50% surgical failure (SF). RESULTS: There was no difference between relative MS extension (Ext) and flexion (Flex) in T1 and T2. There was also, no difference between relative MS Ext and Flex in T1 and T2 between patients with SS and SF. There was a difference in relative MS Ext (144.9 ± 39.8 Nm/kg x 125.5 ± 29.2 Nm/kg; p=0.04) and Flex (73.6 ± 21.8 Nm/kg x 60.4 ± 15.8 Nm/kg; p=0.02) between SS and SF patients only in T2. Patients with an increment in Ext and Flex MS ≥4 Nm/kg at T1 had approximately 76% of SS at 36 months. CONCLUSION: An increase of lower limbs MS ≥4 Nm/kg 6 months after RYGB predicts SS at 36 months. CLINICALTRIALS: gov ID: NCT04129801.

Anthropometric measures and obstructive sleep apnea in children and adolescents: a systematic review of the literature and meta-analysis.

BACKGROUND: Anthropometric measurements can be used to identify children at risk of developing obstructive sleep apnea (OSA). The study aimed to assess which anthropometric measurements (AMs) are most associated with an increased predisposition to develop OSA in healthy children and adolescents. METHODS: We performed a systematic review (PROSPERO #CRD42022310572) that searched eight databases and gray literature. RESULTS: In eight studies with low-to-high risk of bias, investigators reported the following AMs: body mass index (BMI), neck circumference, hip circumference, waist-to-hip ratio, neck-to-waist ratio, waist circumference, waist-to-height ratio, and facial AMs. The meta-analysis showed that the OSA group had an average of 1.00 cm greater for the neck circumference (p < 0.001; Cohen's d = 2.26 [0.72, 5.23]), 3.07 cm greater for the waist circumference (p = 0.030; Cohen's d = 0.28 [0.02, 0.53]), 3.96 cm greater for the hip circumference (p = 0.040; Cohen's d = 0.28 [0.02, 0.55]), 5.21° greater for the cervicomental angle (p = 0.020; Cohen's d = 0.31 [0.03, 0.59]), and 1.23° greater for maxillary-mandibular relationship angle (p < 0.001; Cohen's d = 0.47 [0.22, 0.72]) than the control group. The mandibular depth angle had a reduction of 1.86° (p = 0.001; Cohen's d = -0.36° [-0.65, -0.08]) in control than in patients with OSA. The BMI (p = 0.180), waist-to-hip ratio (p = 0.280), neck-to-waist ratio (p = 0.070), maxillary depth angle (p = 0.250), and upper/lower face height ratio (p = 0.070) showed no significant differences between groups. CONCLUSIONS: Compared to the control group, the OSA group exhibited a greater mean difference in neck circumference, the only anthropometric measurement with high certainty of evidence.

Optimized delay of the second COVID-19 vaccine dose reduces ICU admissions.

Slower than anticipated, COVID-19 vaccine production and distribution have impaired efforts to curtail the current pandemic. The standard administration schedule for most COVID-19 vaccines currently approved is two doses administered 3 to 4 wk apart. To increase the number of individuals with partial protection, some governments are considering delaying the second vaccine dose. However, the delay duration must take into account crucial factors, such as the degree of protection conferred by a single dose, the anticipated vaccine supply pipeline, and the potential emergence of more virulent COVID-19 variants. To help guide decision-making, we propose here an optimization model based on extended susceptible, exposed, infectious, and removed (SEIR) dynamics that determines the optimal delay duration between the first and second COVID-19 vaccine doses. The model assumes lenient social distancing and uses intensive care unit (ICU) admission as a key metric while selecting the optimal duration between doses vs. the standard 4-wk delay. While epistemic uncertainties apply to the interpretation of simulation outputs, we found that the delay is dependent on the vaccine mechanism of action and first-dose efficacy. For infection-blocking vaccines with first-dose efficacy ≥50%, the model predicts that the second dose can be delayed by ≥8 wk (half of the maximal delay), whereas for symptom-alleviating vaccines, the same delay is recommended only if the first-dose efficacy is ≥70%. Our model predicts that a 12-wk second-dose delay of an infection-blocking vaccine with a first-dose efficacy ≥70% could reduce ICU admissions by 400 people per million over 200 d.

Tropane Alkaloid Isolated from Erythroxylum bezerrae Exhibits Neuropharmacological Potential in an Adult Zebrafish (Danio rerio) Model.

This study carried out to investigate the anti-inflammatory and antinociceptive effect of tropane alkaloid (EB7) isolated from E. bezerrae. It evaluated the toxicity and possible involvement of ion channels in the antinociceptive effect of EB7, as well as its anti-inflammatory effect in adult zebrafish (Zfa). Docking studies with EB7 and COX-1 and 2 were also performed. The tested doses of EB7 (4, 20 and 40 mg/kg) did not show any toxic effect on Zfa during the 96h of analysis (LD50>40 mg/kg). They did not produce any alteration in the locomotor behavior of the animals. Furthermore, EB7 showed promising pharmacological effects as it prevented the nociceptive behavior induced by hypertonic saline, capsaicin, formalin and acid saline. EB7 had its analgesic effect blocked by amiloride involving the neuromodulation of ASICs in Zfa. In evaluating the anti-inflammatory activity, the edema induced by κ-carrageenan 3.5 % was reduced by the dose of 40 mg/kg of EB7 observed after the fourth hour of analysis, indicating an effect similar to that of ibuprofen. Molecular docking results indicated that EB7 exhibited better affinity energy when compared to ibuprofen control against the two evaluated targets binding at different sites in the cocrystallized COX-1 and 2 inhibitors.

Neuromodulation of Acid-Sensitive Ion Channels (ASICs) and Anti-Inflammatory Potential by Lichenxanthone in Adult Zebrafish (Danio rerio): Experimental and Docking Studies.

The xanthone lichenxanthone did not show toxic effects (LC50>1.0 mg/mL). lichenxanthone prevented nociceptive behavior induced by acidic saline, and its analgesic effect was blocked by amiloride, highlighting the involvement of neuromodulation of acid-sensitive ion channels (ASICs). In the analysis of anti-inflammatory activity, concentrations of 0.1 and 0.5 mg/mL of lichenxanthone reduced the edema induced by k-carrageenan 3.5 %, observed from the fourth hour of analysis. This effect was similar to that observed with ibuprofen (positive control). No leukocyte infiltrates were observed in lichenxanthone, suggesting that the compound acts in the acute inflammatory response. The results of the molecular docking study revealed that lichenxanthone exhibited better affinity energy when compared to the ibuprofen control against the two targets evaluated.

Withanicandrin Isolated from Datura Ferox Promotes Antinociception by Modulating the Asics and TRPS Channels and Anti-Inflammation in Adult Zebrafish.

This is the first study to analyze the anti-inflammatory and antinociceptive effect of withanicandrin, isolated from Datura Ferox leaves, and the possible mechanism of action involved in adult zebrafish (ZFa). To this end, the animals were treated intraperitoneally (i. p.) with withanicandrin (4; 20 and 40 mg/kg; 20 µL) and subjected to locomotor activity and acute toxicity. Nociception tests were also carried out with chemical agents, in addition to tests to evaluate inflammatory processes induced by κ-Carrageenan 1.5 % and a Molecular Docking study. As a result, withanicandrin reduced nociceptive behavior by capsaicin at a dose of 40 mg/kg and by acid saline at doses of 4 and 40 mg/kg, through neuromodulation of TRPV1 channels and ASICs, identified through blocking the antinociceptive effect of withanicandrin by the antagonists capsazepine and naloxone. Furthermore, withanicandrin caused an anti-inflammatory effect through the reduction of abdominal edema, absence of leukocyte infiltrate in the liver tissue and reduction of ROS in thel liver tissue and presented better affinity energy compared to control morphine (TRPV1) and ibuprofen (COX-1 and COX-2).

Evaluation of condylar and mandibular movements on the upper airway during the use of mandibular advancement device for obstructive sleep apnea treatment.

OBJECTIVES: To evaluate the temporomandibular joint (TMJ), condylar and mandibular movements in obstructive sleep apnea (OSA) patients treated with mandibular advancement device (MAD) and to identify the influence of these anatomic factors on upper airway (UA) volume and polysomnographic outcomes after treatment. MATERIALS AND METHODS: Twenty OSA patients were prospectively treated with MAD. Clinical examinations, cone-beam computed tomography, and polysomnography were performed before MAD treatment and after achieving therapeutic protrusion. Polysomnographic variables and three-dimensional measurements of the TMJ, mandible, and upper airway were statistically analyzed. RESULTS: Condylar rotation, anterior translation, and anterior mandibular displacement were directly correlated with total UA volume, while vertical mandibular translation was inversely correlated with the volume of the inferior oropharynx. MAD treatment resulted in an increase in the volume and area of the superior oropharynx. There was no statistically significant correlation between condylar rotation and translation and polysomnographic variables. With MAD, there was a significant increase in vertical dimension, changes in condylar position (rotation and translation), and mandibular displacement. The central and medial lengths of the articular eminence were inversely correlated with condylar rotation and translation, respectively. The lateral length of the eminence was directly correlated with condylar translation, and the lateral height was directly correlated with condylar rotation and translation. CONCLUSION: Condylar and mandibular movements influenced UA volume. The articular eminence played a role in the amount of condylar rotation and translation. CLINICAL RELEVANCE: Individualized anatomical evaluation of the TMJ proves to be important in the therapy of OSA with MAD.

Cytomegalovirus in Adenoma and Carcinoma Lesions: Detecting Mono-Infection and Co-Infection in Salivary Glands.

Salivary glands' neoplasms are hard to diagnose and present a complex etiology. However, several viruses have been detected in these neoplasms, such as HCMV, which can play a role in certain cancers through oncomodulation. The co-infections between HCMV with betaherpesviruses (HHV-6 and HHV-7) and polyomaviruses (JCV and BKV) has been investigated. The aim of the current study is to describe the frequency of HCMV and co-infections in patients presenting neoplastic and non-neoplastic lesions, including in the salivary gland. Multiplex quantitative polymerase chain reaction was used for betaherpesvirus and polyomavirus quantification purposes after DNA extraction. In total, 50.7% of the 67 analyzed samples were mucocele, 40.3% were adenoma pleomorphic, and 8.9% were mucoepidermoid carcinoma. Overall, 20.9% of samples presented triple-infections with HCMV/HHV-6/HHV-7, whereas 9.0% were co-infections with HCMV/HHV-6 and HCMV/HHV-7. The largest number of co-infections was detected in pleomorphic adenoma cases. All samples tested negative for polyomaviruses, such as BKV and JCV. It was possible to conclude that HCMV can be abundant in salivary gland lesions. A high viral load can be useful to help better understand the etiological role played by viruses in these lesions. A lack of JCV and BKV in the samples analyzed herein does not rule out the involvement of these viruses in one or more salivary gland lesion subtypes.

Ages at peak height velocity in male soccer players 11-16 years: relationships with skeletal age and comparisons among longitudinal studies.

Estimated ages at take-off (TO) and at peak height velocity (PHV) based on two models and maturity status based upon age at PHV and skeletal age (SA) were compared in a longitudinal sample of male soccer players. In addition, estimated ages at PHV in 13 longitudinal samples of soccer players were compared. The longitudinal height records of 58 players of European ancestry, measured annually on four or five occasions between 11 and 16 years, were modeled with Superimposition by Translation and Rotation (SITAR) and Functional Principal Component Analysis (FPCA) to estimate ages at TO and PHV. SAs were assessed with the Fels method. Ages at PHV in 13 longitudinal samples of soccer players (Europe 7, Japan 6) were evaluated with meta-analysis. Estimated ages at TO, 11.2 ± 0.8 (SITAR) and 11.0 ± 0.8 (FCPA) years, and at PHV, 13.6 ± 0.9 (SITAR) and 13.7 ± 0.0 (FCPA) years, were similar. An earlier age at PHV was associated with advanced skeletal maturity status (rho = -0.77 at ~14 years). Ages at PHV among European players indicated a north (later) - south (earlier) gradient, and were later than ages at PHV among Japanese players. In summary, ages at TO and PHV were similar with SITAR and FPCA, and ages at PHV were most strongly correlated with SA at ~14 years. Mean ages at PHV showed a north-south gradient among European samples, and were later compared to Japanese samples.

CLINICAL EFFICACY OF PHOTODYNAMIC THERAPY IN MANAGEMENT OF ORAL POTENTIALLY MALIGNANT DISORDERS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVES: Despite phototherapy (in the form of photodynamic therapy (PDT)-mediated oxidative stress) being utilized in the management of oral potentially malignant disorders (OPMDs), the evidence of certainty remains unclear. Hence, this systematic review and meta-analysis (PROSPERO # CRD42021218748) is aimed to evaluate the clinical efficacy of PDT-induced oxidative stress in OPMDs METHODS: PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases were searched without restriction of language or year of publication. In addition, gray literature was searched and a manual search was performed. Two independent reviewers screened all the studies, assessing data extraction, risk of bias and certainty of evidence. A narrative synthesis was carried out. For the meta-analysis, random effects were considered to determine the prevalence of a total and a partial remission (PR) of oral potentially malignant disorders (OPMDs). The certainty of evidence was explored using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twenty-three studies were included in the qualitative and quantitative syntheses. A total of 880 patients were included (564 males; 218 females) with an age range between 24 and 89-years-old. The results showed the prevalence of the total and partial remissions respectively for the following OPMLs: actinic cheilitis (AC): 69.9% and 2.4%; oral leukoplakia (OL): 44% and 36.9%; oral verrucous hyperplasia (OVH): 98.5%; oral erythroleukoplakia (OEL): 92.1% and 7.9%. The prevalence of no remission of OL was 18.8%. CONCLUSIONS: PDT demonstrated significant results in clinical remission of OPMDs and most of the eligible studies have shown a total or a partial remission of the included lesions, but at a low or a very low certainty of evidence. Hence, further clinical studies with robust methodology are warranted to offer further validated data. Also, further evidence is required to understand further the mechanism of PDT-induced oxidative stress.

Cholesterol-Containing Liposomes Decorated With Au Nanoparticles as Minimal Tunable Fusion Machinery.

Membrane fusion is essential for the basal functionality of eukaryotic cells. In physiological conditions, fusion events are regulated by a wide range of specialized proteins, operating with finely tuned local lipid composition and ionic environment. Fusogenic proteins, assisted by membrane cholesterol and calcium ions, provide the mechanical energy necessary to achieve vesicle fusion in neuromediator release. Similar cooperative effects must be explored when considering synthetic approaches for controlled membrane fusion. We show that liposomes decorated with amphiphilic Au nanoparticles (AuLips) can act as minimal tunable fusion machinery. AuLips fusion is triggered by divalent ions, while the number of fusion events dramatically changes with, and can be finely tuned by, the liposome cholesterol content. We combine quartz-crystal-microbalance with dissipation monitoring (QCM-D), fluorescence assays, and small-angle X-ray scattering (SAXS) with molecular dynamics (MD) at coarse-grained (CG) resolution, revealing new mechanistic details on the fusogenic activity of amphiphilic Au nanoparticles (AuNPs) and demonstrating the ability of these synthetic nanomaterials to induce fusion regardless of the divalent ion used (Ca2+ or Mg2+ ). The results provide a novel contribution to developing new artificial fusogenic agents for next-generation biomedical applications that require tight control of the rate of fusion events (e.g., targeted drug delivery).

A bitter future for coffee production? Physiological traits associated with yield reveal high vulnerability to hydraulic failure in Coffea canephora.

The increase in frequency and intensity of drought events have hampered coffee production in the already threatened Amazon region, yet little is known about key aspects underlying the variability in yield potential across genotypes, nor to what extent higher productivity is linked to reduced drought tolerance. Here we explored how variations in morphoanatomical and physiological leaf traits can explain differences in yield and vulnerability to embolism in 11 Coffea canephora genotypes cultivated in the Western Amazon. The remarkable variation in coffee yield across genotypes was tightly related to differences in their carbon assimilation and water transport capacities, revealing a diffusive limitation to photosynthesis linked by hydraulic constraints. Although a clear trade-off between water transport efficiency and safety was not detected, all the studied genotypes operated in a narrow and/or negative hydraulic safety margin, suggesting a high vulnerability to leaf hydraulic failure (HF), especially on the most productive genotypes. Modelling exercises revealed that variations in HF across genotypes were mainly associated with differences in leaf water vapour leakage when stomata are closed, reflecting contrasting growth strategies. Overall, our results provide a new perspective on the challenges of sustaining coffee production in the Amazon region under a drier and warmer climate.

Functional characterization of a novel PRRT2 variant found in a Portuguese patient with hemiplegic migraine.

Familial hemiplegic migraine (FHM) is a rare autosomal-dominant form of migraine with aura. Three disease-causing genes have been identified for FHM: CACNA1A, ATP1A2 and SCN1A. However, not all families are linked to one of these three genes.PRRT2 variants were also commonly associated with HM symptoms; therefore, PRRT2 is hypothesized as the fourth gene causing FHM. PRRT2 plays an important role in neuronal migration, spinogenesis, and synapse mechanisms during development and calcium-dependent neurotransmitter release. We performed exome sequencing to unravel the genetic cause of migraine in one family, and a novel PRRT2 variant (c.938C > T;p.Ala313Val) was identified with further functional studies to confirm its pathogenicity. PRRT2-A313V reduced protein stability, led to protein premature degradation by the proteasome and altered the subcellular localization of PRRT2 from the plasma membrane (PM) to the cytoplasm. We identified and characterized for the first time in a Portuguese patient, a novel heterozygous missense variant in PRRT2 associated with HM symptoms. We suggest that PRRT2 should be included in the diagnosis of HM.

Simultaneous Electrophysiology and Imaging Reveal Changes in Lipid Membrane Thickness and Tension upon Uptake of Amphiphilic Gold Nanoparticles.

Amphiphilic gold core nanoparticles (AmNPs) striped with hydrophilic 11-mercapto-1-undecanesulfonate (MUS) and hydrophobic 1-octanethiol (OT) ligands are promising candidates for drug carriers that passively and nondisruptively enter cells. Yet, how they interact with cellular membranes is still only partially understood. Herein, we use electrophysiology and imaging to carefully assess changes in droplet interface bilayer lipid membranes (DIBs) incurred by striped AmNPs added via microinjection. We find that AmNPs spontaneously reduce the steady-state specific capacitance and contact angle of phosphatidylcholine DIBs by amounts dependent on the final NP concentration. These reductions, which are greater for NPs with a higher % OT ligands and membranes containing unsaturated lipids but negligible for MUS-only-coated NPs, reveal that AmNPs passively embed in the interior of the bilayer where they increase membrane thickness and lateral tension through disruption of lipid packing. These results demonstrate the enhanced evaluation of nano-bio interactions possible via electrophysiology and imaging of DIBs.

Profile analysis of emerging respiratory virus in children.

Acute respiratory infections (ARIs) are caused by a variety of microorganisms. Of all ARIs, 80% are caused by viruses such as human respiratory syncytial virus, metapneumovirus, influenza, parainfluenza, rhinovirus, and, more recently, Sars-CoV-2, which has been responsible for the COVID-19 pandemic. The objective of our study was to evaluate clinical data from a viral panel performed in children hospitalized with SARS or COVID-19 in the infirmary or ICU of 5 pediatric hospitals in the city of Goiânia, Goiás, Brazil. Demographic, clinical, and laboratory data were collected for analysis, and data on the outcomes underwent statistical treatment. A total of 128 patients were selected for the study, 54% of whom were male and 46% female. The viral panel included rhinovirus, COVID-19, metapneumovirus, adenovirus, and parainfluenza. Descriptive analyses of age profile showed differences in the involvement of particular viruses. The percentage of patients who required hospitalization in the ICU, infirmary, as well as individuals who were discharged after therapy or who died, were described. Our work shows that epidemiological surveillance measures are indispensable, especially if used in the continued analysis of viral panels in all pediatric patients with SARS.