Sex Differences in Chronic Postsurgical Pain after Open Thoracotomy.

STUDY OBJECTIVE: To determine the incidence of chronic postsurgical pain (CPSP) in women after open thoracotomy. Secondary objectives were to compare relevant patient and procedural variables between women and men. DESIGN: Observational cohort study. SETTING: Ten university-affiliated hospitals. SUBJECTS: Ninety-six women and 137 men. INTERVENTIONS: Scheduled open thoracotomy. MEASUREMENTS: Pain histories, psychological measures, and perceived health status and catastrophizing scores were obtained. The diagnosis of chronic postsurgical pain was by physical examination at 4 months. Standard preoperative, intraoperative, and postoperative data were also recorded. MAIN RESULTS: The chronic postsurgical pain incidence was significantly higher in women (53.1%) than in men (38.0%) (p = 0.023). At baseline, women had significantly worse scores on psychological measures (perception of mental state [p = 0.01], depression [p = 0.006], and catastrophizing [p < 0.001]). Women also reported more preoperative pain in the operative area (p = 0.011) and other areas (p = 0.030). CONCLUSION: These findings show that the incidence of physician-diagnosed chronic postsurgical pain is higher in women than in men after surgeries involving thoracotomy. Sex and gender should be included in future clinical research on pain in surgical settings.

Minimum spanning tree analysis of unimpaired individuals at risk of Alzheimer's disease.

Identifying early and non-invasive biomarkers to detect individuals in the earliest stages of the Alzheimer's disease continuum is crucial. As a result, electrophysiology and plasma biomarkers are emerging as great candidates in this pursuit due to their low invasiveness. This is the first magnetoencephalography study to assess the relationship between minimum spanning tree parameters, an alternative to overcome the comparability and thresholding problem issues characteristic of conventional brain network analyses, and plasma phosphorylated tau231 levels in unimpaired individuals, with different risk levels of Alzheimer's disease. Seventy-six individuals with available magnetoencephalography recordings and phosphorylated tau231 plasma determination were included. The minimum spanning tree for the theta, alpha and beta bands for each subject was obtained, and the leaf fraction, tree hierarchy and diameter were calculated. To study the relationship between these topological parameters and phosphorylated tau231, we performed correlation analyses, for the whole sample and considering the two risk sub-groups separately. Increasing concentrations of phosphorylated tau231 were associated with greater leaf fraction and tree hierarchy values, along with lower diameter values, for the alpha and theta frequency bands. These results emerged for the whole sample and the higher risk group, but not for the lower risk group. Our results indicate that the network topology of cognitively unimpaired individuals with elevated plasma phosphorylated tau231 levels, a marker of Alzheimer's disease pathology and amyloid-ß accumulation, is already altered, shifting towards a more integrated network increasing its vulnerability and hub-dependency, mostly in the alpha band. This is indicated by increases in leaf fraction and tree hierarchy, along with reductions in diameter. These results match the initial trajectory proposed by theoretical models of disease progression and network disruption and suggest that changes in brain function and organization begin early on.

Association of Malocclusion with Temporomandibular Disorders: A Cross-Sectional Study.

Background/Objectives: Temporomandibular disorders (TMD) encompass a range of musculoskeletal and neuromuscular conditions affecting the temporomandibular joint (TMJ) and associated structures. This cross-sectional study, conducted in a Portuguese TMD department, aimed to assess the relationship between malocclusion and TMD severity. Methods: Data on demographic variables, TMD clinical symptoms, and malocclusion classes were collected using the EUROTMJ database. The Chi-square test (χ2) identified associations, with their intensity measured by Cramér's V (φc). Results: The study included 1170 patients (932 females and 238 males), with a mean age of 41.73 ± 16.80 years. Most patients exhibited Angle Class I malocclusion (85.5%), followed by Angle Class II (13.5%) and Angle Class III (1.1%). Class II malocclusion was associated with increased TMD severity (p < 0.001), higher myalgia levels (p = 0.002), more frequent disc displacement without reduction (p = 0.002) and lower maximum mouth opening values (Class II: 38.13 ± 7.78 mm, Class I: 39.93 ± 8.67 mm). Significant associations were also found between malocclusion type and arthralgia (p = 0.021), mouth-opening limitation (p = 0.016), and TMJ crepitus (p = 0.017). In cases of malocclusion, the presence of oral signs of bruxism explained the degree of myalgia, disc displacement, and severity (p = 0.003; p = 0.048; p = 0.045). Conclusions: This study highlights that (1) the most common type of dental malocclusion in TMD patients was Class I; (2) Class II malocclusion was associated with increased TMD severity and oral signs of bruxism; and (3) Class III was rarely observed in TMD consultation. The findings suggest that bruxism behavior in cases of malocclusion may be significant in TMD.

Effectiveness of simultaneous bilateral visual diaphragm biofeedback under low back pain: influence of age and sex.

Introduction: The aim of the present study was to determine the effectiveness of simultaneous bilateral visual diaphragm biofeedback (BFB) from ultrasonography in conjunction with inspiratory muscle training (IMT) on diaphragmatic thickness during normal breathing and respiratory and clinical outcomes in patients with non-specific low back pain (NSLBP) and determine the influence of age and sex. Methods: A single-blind randomized clinical trial was carried out (NCT04582812). A total sample of 96 patients with NSLBP was recruited and randomized by sex-based stratification into IMT (n = 48) and BFB + IMT (n = 48) interventions over 8 weeks. Bilateral diaphragmatic thickness at maximum inspiration (Tins) and expiration (Texp), respiratory pressures, lung function, pain intensity, bilateral pressure pain threshold (PPT), disability, and quality of life were measured at baseline and after 8 weeks. Results: The BFB + IMT group showed significant differences (p < 0.05) with increased left hemidiaphragm thickness at Tins and Tins-exp (d = 0.38-053), and right and left PPT (d = 0.71-0.74) versus the IMT group. The interaction with sex was statistically significant (p = 0.007; F(1,81) = 7.756; ηp 2 = 0.087) and higher left hemidiaphragm thickness at Tins was predicted by the BFB + IMT group (R 2 = 0.099; ß = 0.050; F(1,82) = 8.997; p = 0.004) and male sex (R 2 = 0.079; ß = 0.045; F(1,81) = 7.756;p = 0.007). Furthermore, greater left hemidiaphragm thickness at Tins-exp was predicted by younger age (R 2 = 0.052; ß = -0.001; F(1,82) = 4.540; p = 0.036). Discussion: The simultaneous bilateral visual diaphragm biofeedback by ultrasonography in conjunction with IMT was effective in both increasing the left diaphragmatic thickness during inspiration, which was positively influenced and predicted by male sex and younger age, and increasing the bilateral PPT of the paraspinal muscles in patients with NSLBP.

Optimization of TiO2-natural hydrogels for paracetamol and ibuprofen degradation in wastewaters.

Agarose/micrometer titanium dioxide (TiO2) beads were essayed to test the photocatalytic capacity of two of the most widely prescribed drugs worldwide: paracetamol and ibuprofen. Although the initial tests demonstrated promising degradation rates for both drugs, the presence of turbidity, due to TiO2 leakage, during the photocatalytic essays induced to improve the stability of the photocatalytic composites. Among the different strategies adopted to strengthen such materials, crosslinking with citric acid and the use of alternative gelling agents: gellan, agargel™, and agar were chosen. Composites obtained by merging both strategies were characterized and employed to degrade both drugs under a simulated light that mimics the solar spectrum (indoor). Considering the superior degradation rates obtained when agar and agarose were used to shape the titanium oxide particles (up to 70-75% of drug destruction), such composites were subjected to a more realistic experiment (outdoor): solar illumination, tap water, and higher volumes, that should facilitate its ulterior scale up as a real wastewater depollution procedure. Degradation rates between 80 and 90% are attained under such conditions for both drugs.

A case series on a new reference in mandibular angles harmonization: the Frontozygomatic-Infraorbital Line (FZ-IOL).

the aim of this paper, is to propose a new reference line: the Frontozygomatic-Infraorbital Line (FZ-IOL). This reference line can guide the surgical team planning mandibular angle harmonization, based on the patient's skeletal proportion. The Frontozygomatic-Infraorbital Line has been adopted for symmetrization surgery, masculinization surgery, and in unsatisfactory results of previous orthognathic surgery. From March 2021 to December 2022, 3 patients were treated for severe facial asymmetry affecting mainly the lower third of the face. All cases were planned with the reference FZ-IOL. Patients were treated in the same center, at the Orthognathic Surgery Department of the Instituto Portugues da Face, Lisbon, Portugal. The Frontozygomatic-Infraorbital Line is designed virtually using software to reconstruct a 3D image from a digital imaging and communications in medicine (DICOM) file obtained from a cone beam computer tomography (CBCT). , connecting the two orbital rims. Then, a vertical line, the frontozygomatic line perpendicular to the IOL and passing through the outmost lateral portion of the frontozygomatic suture is drawn. The proposed line demonstrated how establishing appropriate reference lines is crucial for the success of the surgery. The selection of reference lines should be based on the patient's anatomy, the symmetrization process's complexity, and the surgery's desired outcome. The Frontozygomatic-Infraorbital Line represents an adequate reference line for managing mandibular angle lateral projection, improving lower third of the face symmetrization.

A Secondary Analysis of Gender Respiratory Features for Ultrasonography Bilateral Diaphragm Thickness, Respiratory Pressures, and Pulmonary Function in Low Back Pain.

The aim of the present study was to determine the gender respiratory differences of bilateral diaphragm thickness, respiratory pressures, and pulmonary function in patients with low back pain (LBP). A sample of 90 participants with nonspecific LBP was recruited and matched paired by sex (45 women and 45 men). Respiratory outcomes included bilateral diaphragm thickness by ultrasonography, respiratory muscle strength by maximum inspiratory (MIP) and expiratory (MEP) pressures, and pulmonary function by forced expiratory volume during 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC spirometry parameters. The comparison of respiratory outcomes presented significant differences (p < 0.001), with a large effect size (d = 1.26-1.58) showing means differences (95% CI) for MIP of -32.26 (-42.99, -21.53) cm H2O, MEP of -50.66 (-64.08, -37.25) cm H2O, FEV1 of -0.92 (-1.18, -0.65) L, and FVC of -1.00 (-1.32, -0.69) L, with lower values for females versus males. Gender-based respiratory differences were presented for maximum respiratory pressures and pulmonary function in patients with nonspecific LBP. Women presented greater inspiratory and expiratory muscle weakness as well as worse lung function, although these differences were not linked to diaphragm thickness during normal breathing.

Artificial-intelligence-model to optimize biocide dosing in seawater-cooled industrial process applications considering environmental, technical, energetic, and economic aspects.

This research introduces an Artificial Intelligence (AI) based model designed to concurrently optimize energy supply management, biocide dosing, and maintenance scheduling for heat exchangers. This optimization considers energetic, technical, economic, and environmental considerations. The impact of biofilm on heat exchangers is assessed, revealing a 41% reduction in thermal efficiency and a 113% increase in flow frictional resistance of the fluid compared to the initial state. Consequently, the pump's power consumption, required to maintain hydraulic conditions, rises by 9%. The newly developed AI model detects the point at which the heat exchanger's performance begins to decline due to accumulating dirt, marking day 44 of experimentation as the threshold to commence the antifouling biocide dosing. Leveraging this AI model to monitor heat exchanger efficiency represents an innovative approach to optimizing antifouling biocide dosing and reduce the environmental impact stemming from industrial plants.

Resting State Electrophysiological Profiles and Their Relationship with Cognitive Performance in Cognitively Unimpaired Older Adults: A Systematic Review.

Background: Aging is a complex and natural process. The physiological decline related to aging is accompanied by a slowdown in cognitive processes, which begins shortly after individuals reach maturity. These changes have been sometimes interpreted as a compensatory sign and others as a fingerprint of deterioration. Objective: In this context, our aim is to uncover the mechanisms that underlie and support normal cognitive functioning in the brain during the later stages of life. Methods: With this purpose, a systematic literature search was conducted using PubMed, Scopus, and Web of Science databases, which identified 781 potential articles. After applying inclusion and exclusion criteria, we selected 12 studies that examined the brain oscillations patterns in resting-state conditions associated with cognitive performance in cognitively unimpaired older adults. Results: Although cognitive healthy aging was characterized differently across studies, and various approaches to analyzing brain activity were employed, our review indicates a relationship between alpha peak frequency (APF) and improved performance in neuropsychological scores among cognitively unimpaired older adults. Conclusions: A higher APF is linked with a higher score in intelligence, executive function, and general cognitive performance, and could be considered an optimal, and easy-to-assess, electrophysiological marker of cognitive health in older adults.

When Maturation is Not Linear: Brain Oscillatory Activity in the Process of Aging as Measured by Electrophysiology.

Changes in brain oscillatory activity are commonly used as biomarkers both in cognitive neuroscience and in neuropsychiatric conditions. However, little is known about how its profile changes across maturation. Here we use regression models to characterize magnetoencephalography power changes within classical frequency bands in a sample of 792 healthy participants, covering the range 13 to 80 years old. Our findings unveil complex, non-linear power trajectories that defy the traditional linear paradigm, with notable cortical region variations. Interestingly, slow wave activity increases correlate with improved cognitive performance throughout life and larger gray matter volume in the elderly. Conversely, fast wave activity diminishes in adulthood. Elevated low-frequency activity during aging, traditionally seen as compensatory, may also signify neural deterioration. This dual interpretation, highlighted by our study, reveals the intricate dynamics between brain oscillations, cognitive performance, and aging. It advances our understanding of neurodevelopment and aging by emphasizing the regional specificity and complexity of brain rhythm changes, with implications for cognitive and structural integrity.

Quorum sensing in bacteria: in silico protein analysis, ecophysiology, and reconstruction of their evolutionary history.

BACKGROUND: Quorum sensing (QS) is a sophisticated cell-to-cell signalling mechanism that allows the coordination of important processes in microbial populations. The AI-1 and AI-2 autoinducer systems are among the best characterized bacterial QS systems at the genetic level. RESULTS: In this study, we present data derived from in silico screening of QS proteins from bacterial genomes available in public databases. Sequence analyses allowed identifying candidate sequences of known QS systems that were used to build phylogenetic trees. Eight categories were established according to the number of genes from the two major QS systems present in each genome, revealing a correlation with specific taxa, lifestyles or metabolic traits. Many species had incomplete QS systems, encoding the receptor protein but not the biosynthesis of the quorum sensing molecule (QSMs). Reconstruction of the evolutionary history of the LuxR family and prediction of the 3D structure of the ancestral protein suggested their monomeric configuration in the absence of the signal molecule and the presence of a cavity for its binding. CONCLUSIONS: Here we correlate the taxonomic affiliation and lifestyle of bacteria from different genera with the QS systems encoded in their genomes. Moreover, we present the first ancestral reconstruction of the LuxR QS receptors, providing further insight in their evolutionary history.

Effects of a respiratory and neurological rehabilitation treatment plan in post Covid-19 affected university students. Randomized clinical study.

BACKGROUND: COVID-19 demonstrated the possibility of neurological complications such as loss of sense of smell and taste, together with respiratory problems. Respiratory training and rehabilitation of neurological sequelae are essential to improve respiratory function and thus quality of life, and the aim of this study is to evaluate the efficacy of a pulmonary and neurological rehabilitation program. OBJECTIVES: To apply a treatment to reduce dyspnea, increase exertional capacity, increase vital capacity and respiratory muscle strength, together with an increase in olfactory and gustatory sensitivity in post-SARS-CoV-2 patients. METHODS: A randomised controlled experimental study was conducted in 220 patients with a medical diagnosis of COVID-19 and more than 5 months of evolution, dyspnoea or perceived fatigue, including olfactory and gustatory perception problems, of whom 200 patients completed the study. 100 patients were randomly assigned to the intervention group, consisting of an inspiratory training treatment plan (Powerbreathe Plus®) combined with aerobic exercise and olfactory gustatory treatment for 31 days, and 100 patients to the control group, for 31 days without any type of therapy. RESULTS: The study was conducted in post-Covid-19 patients for 5 months. Two hundred patients were divided into an intervention group (n = 100) and a control group (n = 100). The comparison between the groups showed significant differences in spirometric variables; forced vital capacity (p < .001; Eta2 (0.439); Mean: 0,6135), the ratio between both FEV1/FVC (p < 0.01; Eta2 (0.728); Mean:9,313), peak inspiratory pressure (p < 0.01; Eta2 (0.906); Mean:4,526); changes were observed in dyspnoea measured with the modified Borg scale (p < 0.01; Eta2 (0.811); Mean:1,481) and the modified Medical Research Council scale (p < 0.01; Eta2 (0.881); Mean: 0.777); finally, changes were found in neurological variables, in the questions of the Singapore Smell and Taste Questionnaire, How was your sense of smell after treatment? (p < 0.01; Eta2 (0.813); Mean: 1,721) and How is your sense of taste after treatment? (p < 0.01; Eta2 (0.898); Mean: 1,088). CONCLUSION: The implementation of a respiratory rehabilitation treatment plan with the Powerbreathe Plus® device, aerobic exercise and neurorehabilitation with olfactory and gustatory training, is a therapeutic option against respiratory and neurological sequelae in patients who have suffered such sequelae due to the SARS-CoV-2 virus. Clinicaltrials.gov: NCT05195099. First posted 18/01/2022; Last Update Posted 29/06/2022.

F-Chin/Feminizing the Chin: A Genioplasty Technique with Virtual Planning for Male-to-Female Transgender Patients.

The chin is an essential structure in facial harmony and an important gender marker. Advancing a receding chin is fundamental to improve the facial appearance, particularly in male-to-female transgender patients. However, in patients with microgenia and/or retrognathia, desiring a more feminine appearance, a chin advancement can result in a wider, square shape; an undesirable effect. Genioplasty is a versatile procedure used in facial feminization surgery that allows modifying the natural anatomy of the chin in all three spatial dimensions. The technique herein described proposes a simple genioplasty procedure for feminizing the chin (F-chin genioplasty) in transgender patients where anteroposterior advance is required. Virtual planning was used to establish the landmarks for an anteroposterior advancement with transverse reduction in the chin. A perpendicular line to the Frankfurt plane passing through the incisal edge of the upper central incisor was used to plan the anteroposterior movement, and two vertical lines on the outer wall of the nasal cavity  for the chin transverse measurement. The authors present three case reports with the F-chin genioplasty transgender technique with satisfactory results, ensuring a more feminine facial appearance.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Genetic underpinnings of arthropod community distributions in Populus trichocarpa.

Community genetics seeks to understand the mechanisms by which natural genetic variation in heritable host phenotypes can encompass assemblages of organisms such as bacteria, fungi, and many animals including arthropods. Prior studies that focused on plant genotypes have been unable to identify genes controlling community composition, a necessary step to predict ecosystem structure and function as underlying genes shift within plant populations. We surveyed arthropods within an association population of Populus trichocarpa in three common gardens to discover plant genes that contributed to arthropod community composition. We analyzed our surveys with traditional single-trait genome-wide association analysis (GWAS), multitrait GWAS, and functional networks built from a diverse set of plant phenotypes. Plant genotype was influential in structuring arthropod community composition among several garden sites. Candidate genes important for higher level organization of arthropod communities had broadly applicable functions, such as terpenoid biosynthesis and production of dsRNA binding proteins and protein kinases, which may be capable of targeting multiple arthropod species. We have demonstrated the ability to detect, in an uncontrolled environment, individual genes that are associated with the community assemblage of arthropods on a host plant, further enhancing our understanding of genetic mechanisms that impact ecosystem structure.

Temporomandibular Joint Minimally Invasive Procedures in the Pediatric Population: A Prospective Study.

Over recent years, temporomandibular joint (TMJ) minimally invasive procedures, such as arthrocentesis and arthroscopy, have been appointed as an initial TMJ intra-articular treatment. Both procedures present safe and effective clinical results in managing temporomandibular disorders (TMD) by reducing pain and improving mouth opening. The use of these techniques in adults is validated in the literature. However, data on the safety and effectiveness of minimally invasive TMJ interventions in pediatric patients are scarce. This study aims to investigate the effectiveness of TMJ arthrocentesis and arthroscopy in the pediatric population. A prospective study was conducted at Instituto Português da Face (IPF) in Lisbon, Portugal, including patients treated for TMD from 1 June 2019 to 30 June 2023. In the present study, 26 patients (17 female and 9 male) were included, representing a total of 48 joints operated. A statistically significant reduction was observed in the primary outcome, TMJ pain, from 3.93 ± 2.80 preoperatively (mean ± SD) to 0.50 ± 1.53 (mean ± SD) postoperatively (p < 0.05). An improvement in the secondary outcome, maximum mouth opening, from 36.92 ± 8.79 preoperatively to 42.96 ± 5.07 postoperatively, was observed (p < 0.05). The overall success rate was 84.62%. This prospective study showed that TMJ arthrocentesis and arthroscopy appear to benefit pediatric patients with TMD, significantly lowering pain and improving MMO without relevant postoperative complications.

Skin Bioimpedance Analysis to Determine Cellular Integrity by Phase Angle in Women with Fibromyalgia: A Cross-Sectional Study.

Oxidative stress has been proposed as a significant part of the pathogenesis of fibromyalgia, and the phase angle in bioelectrical impedance analysis has been explored as a potential technique to screen oxidative abnormalities. This study recruited 35 women with fibromyalgia and 35 healthy women, who underwent bioelectrical impedance analysis and maximum isometric handgrip strength tests. Women with fibromyalgia showed lower bilateral handgrip strength (right hand: 16.39 ± 5.87 vs. 27.53 ± 4.09, p < 0.001; left hand: 16.31 ± 5.51 vs. 27.61 ± 4.14, p < 0.001), as well as higher body fat mass (27.14 ± 10.21 vs. 19.94 ± 7.25, p = 0.002), body fat percentage (37.80 ± 8.32 vs. 30.63 ± 7.77, p < 0.001), and visceral fat area (136.76 ± 55.31 vs. 91.65 ± 42.04, p < 0.01) compared with healthy women. There was no statistically significant difference in muscle mass between groups, but women with fibromyalgia showed lower phase angles in all body regions when compared with healthy control women (right arm: 4.42 ± 0.51 vs. 4.97 ± 0.48, p < 0.01; left arm: 4.23 ± 0.48 vs. 4.78 ± 0.50, p < 0.001; trunk: 5.62 ± 0.77 vs. 6.78 ± 0.84, p < 0.001; right leg: 5.28 ± 0.56 vs. 5.81 ± 0.60, p < 0.001; left leg: 5.07 ± 0.51 vs. 5.69 ± 0.58, p < 0.001; whole body: 4.81 ± 0.47 vs. 5.39 ± 0.49, p < 0.001). Moreover, whole-body phase-angle reduction was only predicted by the presence of fibromyalgia (R2 = 0.264; ß = 0.639; F(1,68) = 24.411; p < 0.001). Our study revealed significantly lower phase angle values, lower handgrip strength, and higher fat levels in women with fibromyalgia compared to healthy controls, which are data of clinical relevance when dealing with such patients.

Differences in Motor Imagery Ability between People with Parkinson's Disease and Healthy Controls, and Its Relationship with Functionality, Independence and Quality of Life.

Motor imagery (MI) has been shown to be effective for the acquisition of motor skills; however, it is still unknown whether similar benefits can be achieved in neurological patients. Previous findings of differences in MI ability between people with Parkinson's disease (PwPD) and healthy controls (HCs) are mixed. This study examined differences in the ability to both create and maintain MI as well as investigating the relationship between the ability to create and maintain MI and motor function, independence and quality of life (QoL). A case-control study was conducted (31 PwPD and 31 HCs), collecting gender, age, dominance, socio-demographic data, duration and impact of the disease. MI intensity (MIQ-RS and KVIQ-34) and temporal accuracy of MI (imagined box and block test [iBBT], imagined timed stand and walk test [iTUG]) were assessed. Functional and clinical assessments included upper limb motor function, balance, gait, independence in activities of daily living and quality of life measures. Statistically significant differences in temporal accuracy were observed and partial and weak relationships were revealed between MI measures and functioning, independence and QoL. PwPD retain the ability to create MI, indicating the suitability of MI in this population. Temporal accuracy might be altered as a reflection of bradykinesia on the mentally simulated actions.

Molecular and functional correction of a deep intronic splicing mutation in CFTR by CRISPR-Cas9 gene editing.

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. The 10th most common mutation, c.3178-2477C>T (3849+10kb C>T), involves a cryptic, intronic splice site. This mutation was corrected in CF primary cells homozygous for this mutation by delivering pairs of guide RNAs (gRNAs) with Cas9 protein in ribonucleoprotein (RNP) complexes that introduce double-strand breaks to flanking sites to excise the 3849+10kb C>T mutation, followed by DNA repair by the non-homologous end-joining pathway, which functions in all cells of the airway epithelium. RNP complexes were delivered to CF basal epithelial cell by a non-viral, receptor-targeted nanocomplex comprising a formulation of targeting peptides and lipids. Canonical CFTR mRNA splicing was, thus, restored leading to the restoration of CFTR protein expression with concomitant restoration of electrophysiological function in airway epithelial air-liquid interface cultures. Off-target editing was not detected by Sanger sequencing of in silico-selected genomic sites with the highest sequence similarities to the gRNAs, although more sensitive unbiased whole genome sequencing methods would be required for possible translational developments. This approach could potentially be used to correct aberrant splicing signals in several other CF mutations and other genetic disorders where deep-intronic mutations are pathogenic.

Effectiveness of double-puncture temporomandibular joint arthrocentesis with viscosupplementation in different categories of severity - a prospective study.

This 3-year prospective study evaluated the efficacy of temporomandibular joint (TMJ) arthrocentesis with viscosupplementation in different severity stages based on the Dimitroulis classification (categories 2-4 were included). TMJ arthrocentesis was performed under local anaesthesia, and the protocol consisted of a double-puncture technique with lavage of ≥150 cc Ringer Lactate plus viscosupplementation. Incobotulinum toxin A was administered 10-15 days preoperatively in patients with concomitant masticatory myalgia. The primary outcome was TMJ pain, assessed by visual analogue scale (VAS, 0-10), and the secondary outcomes were the maximum mouth opening (MMO, mm) and myalgia degree (0-3). All outcomes were assessed on the intervention day (T0) and after the procedure (T1) (minimum 1 month and then 3 months, 6 months, 1 year and every year since). A total of 108 patients were enrolled (mean age of 43.1 ± 18.9 years); 86 (80%) were women and 22 (20%) were men. Preoperative pain was 4.02 ± 3.12 (mean ± SD), MMO was 38.10 ± 9.56 (mean ± SD) and myalgia degree was 1.80 ± 1.18 (mean ± SD). After an average of 215.4 days (31-1253 days), a statistically significant improvement of pain (P < 0.0001), MMO (P = 0.005) and myalgia degree (P < 0.0001) was observed. The overall successful outcome of TMJ arthrocentesis with viscosupplementation was 76%. The authors observed increased arthrocentesis effectiveness and success rate with viscosupplementation in Dimitroulis category 2 (88.6%) compared to 3-4 (71.4%). An association was found between arthrocentesis with viscosupplementation failure and painful myalgia (ρ = 0.477; P < 0.0001). Thirteen patients (12%) underwent a second TMJ intervention after finalising the present trial. With a low complication rate, TMJ arthrocentesis with viscosupplementation led to an overall benefit for all the included patients. This study reinforces the important role of minimally invasive TMJ arthrocentesis as a first treatment option, with better results in the early stages compared to more severe stages.

Therapeutic Exercise Parameters, Considerations and Recommendations for the Treatment of Non-Specific Low Back Pain: International DELPHI Study.

BACKGROUND: Therapeutic exercise (TE) recommendations for non-specific low back pain (LBP) are meant to support therapy choices for people who suffer from this condition. The aim of this study was to reach an agreement on the definition and use of TE in the care of people with LBP. METHODS: A Delphi study was carried out with a formal consensus procedure and sufficient scientific evidence, using an established methodology. Four rounds of anonymous questionnaires were administered to create useful suggestions and instructions in terms of the therapeutic activity for patients with LBP, and a group consensus conference. RESULTS: A consensus was reached on most of the questions after 35 physiotherapists completed the questionnaires. Participants agreed that proper TE requires correct posture, body awareness, breathing, movement control, and instruction. Patients with LBP were advised to participate in supervised sessions twice a week for 30 to 60 min for a period of 3 to 6 months. Participants added that tailored evaluation and exercise prescription, monitoring, and functional integration of exercise, as well as using specific equipment, would benefit patients with LBP. CONCLUSIONS: TE recommendations for patients with LBP should be dosed and customized based on their personal psychological needs, level of fitness, and kinesiophobia.