Validation of Math Model Using Porous Media for Determining Alveolar CO 2 in Ventilated Patients.

OBJECTIVES: To validate a mathematical model using porous media theory for alveolar CO2 determination in ventilated patients. DESIGN: Mathematical modeling study with prospective clinical validation to simulate CO2 exchange from bloodstream to airway entrance. SETTING: ICU. PATIENTS: Thirteen critically ill patients without chronic or acute lung disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Model outcomes compared with patient data showed correlations for end-tidal CO2 (EtCO 2 ), area under the CO2 curve, and Pa CO2 of 0.918, 0.954, and 0.995. Determination coefficients ( R2 ) were 0.843, 0.910, and 0.990, indicating precision and predictive power. CONCLUSIONS: The mathematical model shows potential in pulmonary critical care. Although promising, practical application demands further validation, clinician training, and patient-specific adjustments. The path to clinical use will be iterative, involving validation and education.

Laparoscopic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy, an Update From the International PSOGI Registry.

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are established treatments for peritoneal surface malignancies, traditionally performed via laparotomy. Recent advancements in laparoscopic approaches (L-CRS + HIPEC) have shown promising results in selected patients. METHODS: The PSOGI registry, established in November 2019, collects data from specialized centers performing L-CRS + HIPEC. Data were collected prospectively and analyzed retrospectively, excluding risk-reducing procedures without peritoneal disease. The learning curve was assessed using a 14-cases cutoff. RESULTS: Today, 323 patients have been registered, 193 were included finally. Perioperative outcomes improved after 14 cases: Length of hospital stay was 7.78 ± 3.64 days (consolidation) versus 8.8 ± 8.79 days (learning) and major morbidity was 0% (consolidation) versus 5% (learning), (p = n.s.). Estimated blood loss was lower in the consolidation phase. Oncological outcomes also improved: Recurrence rate was 8.7% (consolidation) versus 17.8% (learning). Disease-free survival 5 years, 65% (learning) versus 88% (consolidation) (p = 0.012). CONCLUSION: The L-CRS + HIPEC is a safe procedure with non-inferior oncologic outcomes which it is evaluating in an IDEAL setting by an international group. The validation of the learning curve, gives us the knowledge that a mentoring program must be setup to reduce the learning curve impact in oncologic failure.

Early focal electroencephalogram and neuroimaging findings predict epilepsy development after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Seizures are a common complication of subarachnoid hemorrhage (SAH) in both acute and late stages: 10-20 % acute symptomatic seizures, 12-25 % epilepsy rate at five years. Our aim was to identify early electroencephalogram (EEG) and computed tomography (CT) findings that could predict long-term epilepsy after SAH. MATERIAL AND METHODS: This is a multicenter, retrospective, longitudinal study of adult patients with aneurysmal SAH admitted to two tertiary care hospitals between January 2011 to December 2022. Routine 30-minute EEG recording was performed in all subjects during admission period. Exclusion criteria were the presence of prior structural brain lesions and/or known epilepsy. We documented the presence of SAH-related cortical involvement in brain CT and focal electrographic abnormalities (epileptiform and non-epileptiform). Post-SAH epilepsy was defined as the occurrence of remote unprovoked seizures ≥ 7 days from the bleeding. RESULTS: We included 278 patients with a median follow-up of 2.4 years. The mean age was 57 (+/-12) years, 188 (68 %) were female and 49 (17.6 %) developed epilepsy with a median latency of 174 days (IQR 49-479). Cortical brain lesions were present in 189 (68 %) and focal EEG abnormalities were detected in 158 patients (39 epileptiform discharges, 119 non-epileptiform abnormalities). The median delay to the first EEG recording was 6 days (IQR 2-12). Multiple Cox regression analysis showed higher risk of long-term epilepsy in those patients with CT cortical involvement (HR 2.6 [1.3-5.2], p 0.009), EEG focal non-epileptiform abnormalities (HR 3.7 [1.6-8.2], p 0.002) and epileptiform discharges (HR 6.7 [2.8-15.8], p < 0.001). Concomitant use of anesthetics and/or antiseizure medication during EEG recording had no influence over its predictive capacity. ROC-curve analysis of the model showed good predictive capability at 5 years (AUC 0.80, 95 %CI 0.74-0.87). CONCLUSIONS: Focal electrographic abnormalities (both epileptiform and non-epileptiform abnormalities) and cortical involvement in neuroimaging predict the development of long-term epilepsy. In-patient EEG and CT findings could allow an early risk stratification and facilitate a personalized follow-up and management of SAH patients.

Early diverting stoma closure is feasible and safe: results from a before-and-after study on the implementation of an early closure protocol at a tertiary referral center.

BACKGROUND: Evidence on early closure (EC) of defunctioning stoma (DS) after colorectal surgery shows a favorable effect when patients are carefully selected. Therefore, a clinical pathway adapted to the implementation of an EC strategy was developed in our center. The aim of this study was to carry out a comparative analysis of time until DS closure and DS-related morbidity before and after the implementation of an EC protocol (ECP). METHODS: This study is a before-and-after comparative analysis. Patients were divided into two cohorts according to the observational period: patients from the period before the ECP implementation (January 2015-December 2019) [Period 1] and those from the period after that (January 2020-December 2022) [Period 2]. All consecutive patients subjected to elective DS closure within both periods were eligible. Early closure was defined as the reversal within 30 days from DS creation. Patients excluded from EC or those not closed within 30 days since primary surgery were analyzed as late closure (LC). Baseline characteristics and DS-related morbidity were recorded. RESULTS: A total of 145 patients were analyzed. Median time with DS was shorter in patients after ECP implementation [42 (21-193) days versus 233 (137-382) days, p < 0.001]. This reduction in time to closure did not impact the DS closure morbidity and resulted in less DS morbidity (68.8% versus 49.2%, p = 0.017) and fewer stoma nurse visits (p = 0.029). CONCLUSIONS: The ECP was able to significantly reduce intervals to restoration of bowel continuity in patients with DS, which in turn resulted in a direct impact on the reduction of DS morbidity without negatively affecting DS closure morbidity.

Regulation of human oocyte maturation in vivo during the final maturation of follicles.

STUDY QUESTION: Which substances and signal transduction pathways are potentially active downstream to the effect of FSH and LH in the regulation of human oocyte maturation in vivo? SUMMARY ANSWER: The regulation of human oocyte maturation appears to be a multifactorial process in which several different signal transduction pathways are active. WHAT IS KNOWN ALREADY: Many studies in animal species have provided insight into the mechanisms that govern the final maturation of oocytes. Currently, these studies have identified several different mechanisms downstream to the effects of FSH and LH. Some of the identified mechanisms include the regulation of cAMP/cGMP levels in oocytes involving C-type natriuretic peptide (CNP), effects of epidermal growth factor (EGF)-related peptides such as amphiregulin (AREG) and/or epiregulin (EREG), effect of TGF-ß family members including growth differentiation factor 9 (GDF9) and morphogenetic protein 15 (BMP15), activins/inhibins, follicular fluid meiosis activating sterol (FF-MAS), the growth factor midkine (MDK), and several others. However, to what extent these pathways and mechanisms are active in humans in vivo is unknown. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 50 women undergoing fertility treatment in a standard antagonist protocol at a university hospital affiliated fertility clinic in 2016-2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: We evaluated the substances and signalling pathways potentially affecting human oocyte maturation in follicular fluid (FF) and granulosa cells (GCs) collected at five time points during the final maturation of follicles. Using ELISA measurement and proteomic profiling of FF and whole genome gene expression in GC, the following substances and their signal transduction pathways were collectively evaluated: CNP, the EGF family, inhibin-A, inhibin-B, activins, FF-MAS, MDK, GDF9, and BMP15. MAIN RESULTS AND THE ROLE OF CHANCE: All the evaluated substances and signal transduction pathways are potentially active in the regulation of human oocyte maturation in vivo except for GDF9/BMP15 signalling. In particular, AREG, inhibins, and MDK were significantly upregulated during the first 12-17 h after initiating the final maturation of follicles and were measured at significantly higher concentrations than previously reported. Additionally, the genes regulating FF-MAS synthesis and metabolism were significantly controlled in favour of accumulation during the first 12-17 h. In contrast, concentrations of CNP were low and did not change during the process of final maturation of follicles, and concentrations of GDF9 and BMP15 were much lower than reported in small antral follicles, suggesting a less pronounced influence from these substances. LARGE SCALE DATA: None. LIMITATIONS, REASONS FOR CAUTION: Although GC and cumulus cells have many similar features, it is a limitation of the current study that information for the corresponding cumulus cells is not available. However, we seldom recovered a cumulus-oocyte complex during the follicle aspiration from 0 to 32 h. WIDER IMPLICATIONS OF THE FINDINGS: Delineating the mechanisms governing the regulation of human oocyte maturation in vivo advances the possibility of developing a platform for IVM that, as for most other mammalian species, results in healthy offspring with good efficacy. Mimicking the intrafollicular conditions during oocyte maturation in vivo in small culture droplets during IVM may enhance oocyte nuclear and cytoplasmic maturation. The primary outlook for such a method is, in the context of fertility preservation, to augment the chances of achieving biological children after a cancer treatment by subjecting oocytes from small antral follicles to IVM. Provided that aspiration of oocytes from small antral follicles in vivo can be developed with good efficacy, IVM may be applied to infertile patients on a larger scale and can provide a cheap alternative to conventional IVF treatment with ovarian stimulation. Successful IVM has the potential to change current established techniques for infertility treatment. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the University Hospital of Copenhagen, Rigshospitalet, the Independent Research Fund Denmark (grant number 0134-00448), and the Interregional EU-sponsored ReproUnion network. There are no conflicts of interest to be declared.

Protocol for the SEHNeCa randomised clinical trial assesing Supervised Exercise for Head and Neck Cancer patients.

OBJECTIVES: To evaluate the effectiveness of an innovative supervised exercise programme to mitigate the loss of lean body mass, functional capacity and quality of life in people with head and neck cancer, as well as to identify the optimal moment to apply it, before or after radiotherapy treatment, compared with the prescription of a physical activity plan carried out autonomously. METHODS: Patients with squamous cell carcinoma of the head and neck (n = 144), treated with radiotherapy, will be randomly assigned to one of 3 comparison groups: pre-radiotherapy supervised exercise, post-radiotherapy supervised exercise and autonomous exercise, stratifying by human papillomavirus infection and previous surgery. The exercise programme will be carried out in 36 sessions over 12 weeks, combining moderate and high intensity strength and aerobic exercises. The main outcome variable is the change in lean body mass at 6 months measured by bioimpedance, while secondary variables are functional capacity, symptoms, quality of life and adverse effects. Longitudinal generalised mixed models will be used for the analyses of the repeated measurements at 3, 6, and 12 months after baseline. CONCLUSIONS: The pilot study supports the feasibility and safety of the project. However, as the programme progressed, attendance at the sessions decreased. Strategies will be necessary for increasing attendance, as well as involving the patient in their recovery and other incentives. Follow-up after treatment to assess acute/late toxicity will enable us to know the response to both the exercise programme and its adherence. TRIAL REGISTRATION: NCT04658706 Date and version identifier: March 1, 2023. Version 1.1.

Prevalence, risk factors and evolution of diabetes mellitus after treatment in primary aldosteronism. Results from the SPAIN-ALDO registry.

PURPOSE: To evaluate the prevalence, risk factors and evolution of diabetes mellitus (DM) after targeted treatment in patients with primary aldosteronism (PA). METHODS: A retrospective multicenter study of PA patients in follow-up at 27 Spanish tertiary hospitals (SPAIN-ALDO Register). RESULTS: Overall, 646 patients with PA were included. At diagnosis, 21.2% (n = 137) had DM and 67% of them had HbA1c levels < 7%. In multivariate analysis, family history of DM (OR 4.00 [1.68-9.53]), the coexistence of dyslipidemia (OR 3.57 [1.51-8.43]) and advanced age (OR 1.04 per year of increase [1.00-1.09]) were identified as independent predictive factors of DM. Diabetic patients were on beta blockers (46.7% (n = 64) vs. 27.5% (n = 140), P < 0.001) and diuretics (51.1% (n = 70) vs. 33.2% (n = 169), p < 0.001) more frequently than non-diabetics. After a median follow-up of 22 months [IQR 7.5-63.0], 6.9% of patients developed DM, with no difference between those undergoing adrenalectomy and those treated medically (HR 1.07 [0.49-2.36], p = 0.866). There was also no significant difference in the evolution of glycemic control between DM patients who underwent surgery and those medically treated (p > 0.05). CONCLUSION: DM affects about one quarter of patients with PA and the risk factors for its development are common to those of the general population. Medical and surgical treatment provides similar benefit in glycemic control in patients with PA and DM.

The 2021 SIIM-FISABIO-RSNA Machine Learning COVID-19 Challenge: Annotation and Standard Exam Classification of COVID-19 Chest Radiographs.

We describe the curation, annotation methodology, and characteristics of the dataset used in an artificial intelligence challenge for detection and localization of COVID-19 on chest radiographs. The chest radiographs were annotated by an international group of radiologists into four mutually exclusive categories, including "typical," "indeterminate," and "atypical appearance" for COVID-19, or "negative for pneumonia," adapted from previously published guidelines, and bounding boxes were placed on airspace opacities. This dataset and respective annotations are available to researchers for academic and noncommercial use.

Stationary flow driven by non-sinusoidal time-periodic pressure gradients in wavy-walled channels.

The classical problem of secondary flow driven by a sinusoidally varying pressure gradient is extended here to address periodic pressure gradients of complex waveform, which are present in many oscillatory physiological flows. A slender two-dimensional wavy-walled channel is selected as a canonical model problem. Following standard steady-streaming analyses, valid for small values of the ratio ε of the stroke length of the pulsatile motion to the channel wavelength, the spatially periodic flow is described in terms of power-law expansions of ε, with the Womersley number assumed to be of order unity. The solution found at leading order involves a time-periodic velocity with a zero time-averaged value at any given point. As in the case of a sinusoidal pressure gradient, effects of inertia enter at the following order to induce a steady flow in the form of recirculating vortices with zero net flow rate. An improved two-term asymptotic description of this secondary flow is sought by carrying the analysis to the following order. It is found that, when the pressure gradient has a waveform with multiple harmonics, the resulting velocity corrections display a nonzero flow rate, not present in the single-frequency case, which enables stationary convective transport along the channel. Direct numerical simulations for values of ε of order unity are used to investigate effects of inertia and delineate the range of validity of the asymptotic limit ε≪1. The comparisons of the time-averaged velocity obtained numerically with the two-term asymptotic description reveals that the latter remains remarkably accurate for values of ε exceeding 0.5. As an illustrative example, the results of the model problem are used to investigate the cerebrospinal-fluid flow driven along the spinal canal by the cardiac and respiratory cycles, characterized by markedly non-sinusoidal waveforms.

A critical review of textile industry wastewater: green technologies for the removal of indigo dyes.

The denim textile industry represents an important productive sector. It generates wastewater with low biodegradability due to the presence of persistent pollutants, which can produce toxic and carcinogenic compounds; therefore, wastewater treatment reduces risks to aquatic life and public health. This paper presents a review of 172 papers regarding textile industry wastewater treatment for the removal of contaminants, especially indigo dyes used in the denim industry, in the context of green technologies. The physicochemical characteristics of textile wastewater, its environmental and health impacts, and the permissible limit regulations in different countries were reviewed. Biological, physicochemical and advanced oxidation processes for the removal of indigo dyes were reviewed. The goal of this study was to analyze the characteristics of green technologies; however, the research does not clearly demonstrate an effect on energy consumption savings, carbon footprint decreases, and/or waste generation. Advanced oxidation processes showed the highest color removal efficiency (95 and 97% in synthetic or real wastewater, respectively). Photocatalysis and Fenton reactions were the most efficient processes. None of the revised works presented results regarding upscaling for industrial application, and the results should be discussed in terms of the guidelines and maximum permissible limits established by international legislation. New technologies need to be developed and evaluated in a sustainable context with real wastewater.

ScipionTomo: Towards cryo-electron tomography software integration, reproducibility, and validation.

Image processing in cryogenic electron tomography (cryoET) is currently at a similar state as Single Particle Analysis (SPA) in cryogenic electron microscopy (cryoEM) was a few years ago. Its data processing workflows are far from being well defined and the user experience is still not smooth. Moreover, file formats of different software packages and their associated metadata are not standardized, mainly since different packages are developed by different groups, focusing on different steps of the data processing pipeline. The Scipion framework, originally developed for SPA (de la Rosa-Trevín et al., 2016), has a generic python workflow engine that gives it the versatility to be extended to other fields, as demonstrated for model building (Martínez et al., 2020). In this article, we provide an extension of Scipion based on a set of tomography plugins (referred to as ScipionTomo hereafter), with a similar purpose: to allow users to be focused on the data processing and analysis instead of having to deal with multiple software installation issues and the inconvenience of switching from one to another, converting metadata files, managing possible incompatibilities, scripting (writing a simple program in a language that the computer must convert to machine language each time the program is run), etcetera. Additionally, having all the software available in an integrated platform allows comparing the results of different algorithms trying to solve the same problem. In this way, the commonalities and differences between estimated parameters shed light on which results can be more trusted than others. ScipionTomo is developed by a collaborative multidisciplinary team composed of Scipion team engineers, structural biologists, and in some cases, the developers whose software packages have been integrated. It is open to anyone in the field willing to contribute to this project. The result is a framework extension that combines the acquired knowledge of Scipion developers in close collaboration with third-party developers, and the on-demand design of functionalities requested by beta testers applying this solution to actual biological problems.

Prediction of molecular mimicry between proteins from Trypanosoma sp. and human antigens associated with systemic lupus erythematosus.

The immune response against pathogens induces protection from future infection, however, molecular mimicry between the pathogen and the human host can promote autoreactive responses. Using in silico approaches, we identified molecular mimicry between Trypanosoma sp. and human autoantigens involved in the development of systemic lupus erythematosus (SLE). We retrieved all reported autoantigen amino acid sequences for SLE from the AAgAtlas database to perform PSI-BLAST against the Trypanosoma sp proteome to determine amino acid sequence identity with each other. The antigens given in the Protein Data Bank without a 3D structure were modeled by homology with the "Swiss Modeller Server". Epitopes shared between Trypanosoma sp. and human antigens were identified using the Ellipro server and the Immune Epitope Database (IEDB), and cross-reactive epitopes were assigned to the 3D models. 36 autoantigens involved in SLE showed molecular mimicry with Trypanosoma sp. Antigens Epitope prediction revealed that some autoantigens shared several antigenic.

Mid-infrared photoluminescence revealing internal quantum efficiency enhancement of type-I and type-II InAs core/shell nanowires.

Internal quantum efficiency (IQE) is an important figure of merit for photoelectric applications. While the InAs core/shell (c/s) nanowire (NW) is a promising solution for efficient quantum emission, the relationship between the IQE and shell coating remains unclear. This Letter reports mid-infrared PL measurements on InAs/InGaAs, InAs/AlSb, and InAs/GaSb c/s NWs, together with bare InAs NWs as a reference. Analyses show that the IQE is depressed by a shell coating at 9 K but gets improved by up to approximately 50% for the InGaAs shell coating at 40 -140 K and up to approximately 20% beyond 110 K for the AlSb shell. The effect is ascribed not only to the crystal quality but more importantly to the radial band alignment. The result indicates the high-temperature IQE improvement of the type-I and type-II c/s NWs and the appropriateness of the mid-infrared PL analyses for narrow-gap NW evaluation.

Mid-infrared photoluminescence revealing internal quantum efficiency enhancement of type-I and type-II InAs core/shell nanowires: publisher's note.

This publisher's note contains corrections to Opt. Lett.47, 5208 (2022)10.1364/OL.473154.

The Biosynthesis of Penicillin and Cephalosporin C are Regulated by ROS at Transcriptional Level.

In a recent work we showed that, besides lovastatin, ROS also accumulate during the production phase in Pencillium chrysogenum and in Acremonium chrysogenum, and that these ROS regulate the biosynthesis of penicillin and cephalosporin C. In the present study, we investigated the level at which this positive regulation is exerted. Internal ROS levels were manipulated, i.e., increased or decreased, in the production phase of the respective fermentations. Penicillin production decreased by 51.2% when internal ROS concentration was diminished by 50%, while a 62% production increase was observed when ROS were increased (62%). Similarly, Cephalosporin production decreased (35%) with antioxidants and increased (54.1%) with exogenous ROS. Expression analysis of the respective pcbAB genes, encoding the non-ribosomal peptide synthetase enzymes, was performed. Results showed down regulation of these genes in fermentations with lower ROS content, and upregulation in the cultures with higher ROS content, in both species. This showed that ROS regulation of penicillin in P. chrysogenum and of cephalosporin C in A. chrysogenum, is exerted at transcriptional level. In silico analysis of the pcbAB gene promoters in both species, suggested that this regulation could be mediated by stress-response transcription factors like Yap1, SrrA and/or MsnA, and/or by the Hap complex.

Initial experience with intraoperative testing and repair of colorectal anastomosis using a TAMIS approach after a positive leak test.

Anastomotic leak is one of the most feared complications of colorectal anastomosis. Different techniques have been described for intraoperative testing of anastomotic integrity. These include air insufflation, methylene blue and endoscopic visualisation. If an anastomotic leak is identified intraoperatively, there are various management options. Redo anastomosis is a possibility, but may be difficult in some cases. Defunctioning is another option, but there is an associated morbidity and signficant detrimental effect on quality of life. Direct transanal repair is only possible when a low anastomosis has been performed. When the anastomotic leak occurs high in the rectum or a partial mesorectal excision is performed a transanal approach is technically very challenging. We present our experience with transanal minimally invasive surgery (TAMIS) approach for anastomotic assessment and repair in four patients. In all cases, a colorectal anastomosis was performed and the air insufflation test was positive. We assessed the anastomosis with TAMIS. In three cases, a defect was found and subsequently sutured. In one case, a scar in the rectal mucosa was found and reinforced with a suture. A protective ileostomy was performed in two cases, while in the other two cases, no stoma was added. All four patients were discharged with no further complications. Both protective ileostomies were taken down after radiological and endoscopic confirmation of anastomotic integrity and all 4 anastomoses remain intact after follow-up. TAMIS intraoperative assessment and repair of anastomotic leak is a safe and feasible technique whcih may avoid the need for a defunctioning stoma.

Characterisation of clays from Alicante province (SE Spain) for use in the recovery of degraded soils.

The goal of this paper is the characterisation of seven clays of the province of Alicante (SE Spain) and their possible use to improve the fertility, water absorption and contaminant-retaining capacity of degraded soils. Three soils affected by the dumping of construction debris were also studied to diagnose the problems and possible recovery strategies. Several physicochemical properties were measured, such as the water holding capacity, soil organic matter, lime, pH, EC and CEC. A high correlationship between mineralogical and elemental composition was obtained. Illite was present in all clays and soils. Some of the samples also contained kaolinite and significant amounts of lime. The CEC, as expected, was more closely related to the organic matter content. Soil organic matter was detected in the second derivative of the FTIR spectra by the signals of the CH2 groups at 2850 and 2919. This way, the FTIR spectrum for the soils of the area would make it possible to estimate both the organic matter content and the CEC. Despite their origin, soils did not show heavy metal pollution; however, salinisation risk seemed to be the most probable cause of degradation. According to the organic matter, lime and illite content, two clays were selected as the most suitable for soil degradation recovery. Furthermore, organic matter additions may help to improve the self-depurative ability of the soil.

Heterozygous CAPN3 missense variants causing autosomal-dominant calpainopathy in seven unrelated families.

AIMS: Recessive variants in CAPN3 gene are the cause of the commonest form of autosomal recessive limb girdle muscle dystrophy. However, two distinct in-frame deletions in CAPN3 (NM_000070.3:c.643_663del21 and c.598_621del15) and more recently, Gly445Arg and Arg572Pro substitutions have been linked to autosomal dominant (AD) forms of calpainopathy. We report 21 affected individuals from seven unrelated families presenting with an autosomal dominant form of muscular dystrophy associated with five different heterozygous missense variants in CAPN. METHODS: We have used massively parallel gene sequencing (MPS) to determine the genetic basis of a dominant form of limb girdle muscular dystrophy in affected individuals from seven unrelated families. RESULTS: The c.700G> A, [p.(Gly234Arg)], c.1327T> C [p.(Ser443Pro], c.1333G> A [p.(Gly445Arg)], c.1661A> C [p.(Tyr554Ser)] and c.1706T> C [p.(Phe569Ser)] CAPN3 variants were identified. Affected individuals presented in young adulthood with progressive proximal and axial weakness, waddling walking and scapular winging or with isolated hyperCKaemia. Muscle imaging showed fatty replacement of paraspinal muscles, variable degrees of involvement of the gluteal muscles, and the posterior compartment of the thigh and minor changes at the mid-leg level. Muscle biopsies revealed mild myopathic changes. Western blot analysis revealed a clear reduction in calpain 3 in skeletal muscle relative to controls. Protein modelling of these variants on the predicted structure of calpain 3 revealed that all variants are located in proximity to the calmodulin-binding site and are predicted to interfere with proteolytic activation. CONCLUSIONS: We expand the genotypic spectrum of CAPN3-associated muscular dystrophy due to autosomal dominant missense variants.

Toward high laser power beam manipulation with nanophotonic materials: evaluating thin film damage performance.

Nanophotonic materials enable unprecedented control of light-matter interactions, including the ability to dynamically steer or shape wavefronts. Consequently, nanophotonic systems such as metasurfaces have been touted as promising candidates for free-space optical communications, directed energy and additive manufacturing, which currently rely on slow mechanical scanners or electro-optical components for beam steering and shaping. However, such applications necessitate the ability to support high laser irradiances (> kW/cm2) and systematic studies on the high-power laser damage performance of nanophotonic materials and designs are sparse. Here, we experimentally investigate the pulsed laser-induced damage performance (at λ ∼ 1 µm) of model nanophotonic thin films including gold, indium tin oxide, and refractory materials such as titanium nitride and titanium oxynitride. We also model the spatio-thermal dissipation dynamics upon single-pulse illumination by anchoring experimental laser damage thresholds. Our findings show that gold exhibits the best laser damage resistance, but we argue that alternative materials such as transparent conducting oxides could be optimized to balance the tradeoff between damage resistance and optical tunability, which is critical for the design of thermally robust nanophotonic systems. We also discuss damage mitigation and ruggedization strategies for future device-scale studies and applications requiring high power beam manipulation.

Cytokines and growth factors in a biologic product obtained from patients' urine as immune-modulators to treat autoimmune and allergic diseases.

At "Instituto de Alergias y Autoinmunidad Dr. Maximiliano Ruiz Castañeda, A.C." in Mexico City, a non-traditional health care center focused on the treatment of autoimmune and allergic diseases using personalized medicine, an alternative treatment referred to as an "immune-modulator" has been developed. In this study, we will refer to this treatment substance as the "immune-modulator." In brief, a urine sample is collected from the patient and processed to obtain the peptide fraction, which is conditioned and then administered sublingually to the patient. Sample processing involves multiple steps aimed at the removal of toxic compounds and enrichment for cytokines, growth factors, and other immune peptides that may contribute to the function of the immune-modulator. This treatment has been administered for many years, and patients testify that it is useful and reliable. Despite the benefits of this treatment, the molecular mechanisms underlying its effects have not been thoroughly investigated. Therefore, this study aims to identify immunoregulatory peptides, such as cytokines and growth factors, in the immune-modulator. Urine and immune-modulator concentrations of cytokines and growth factors were assessed using a Luminex assay. Twenty-one cytokines and growth factors were identified in immune-modulator samples. MCP-1 was identified in 100% of the samples; MIP-1ß, IL-8, RANTES, INF-γ, and IP-10 were identified in approximately 65-70% of samples; IL5, IL-1B, and IL-17 in 50-60%; eotaxin, VEGF, IL-6, and FGF in about 40%; MIP-1α, IL-9, GM-CSF, G-CSF, IL-12, and IL-15 in about 20-30%; and IL-13 and PDGF-bb were identified in <6% of samples. Additionally, patients exhibited significant changes in IL-1ß, IFN-γ, and MCP-1 concentrations after treatment with the immune-modulator, whereas healthy individuals showed no significant change in response to the treatment. The immune-modulator is an alternative treatment based on the administration of cytokines and growth factors obtained from the urine of patients. In this study, its composition was characterized. The isolated products could be responsible for the effects of the immune-modulator. Further trials are required to evaluate the effective delivery of these molecules by the administration route described.