Tandem-repeat lectins: structural and functional insights.

Multivalency in lectins plays a pivotal role in influencing glycan cross-linking, thereby affecting lectin functionality. This multivalency can be achieved through oligomerization, the presence of tandemly repeated carbohydrate recognition domains, or a combination of both. Unlike lectins that rely on multiple factors for the oligomerization of identical monomers, tandem-repeat lectins inherently possess multivalency, independent of this complex process. The repeat domains, although not identical, display slightly distinct specificities within a predetermined geometry, enhancing specificity, affinity, avidity and even oligomerization. Despite the recognition of this structural characteristic in recently discovered lectins by numerous studies, a unified criterion to define tandem-repeat lectins is still necessary. We suggest defining them multivalent lectins with intrachain tandem repeats corresponding to carbohydrate recognition domains, independent of oligomerization. This systematic review examines the folding and phyletic diversity of tandem-repeat lectins and refers to relevant literature. Our study categorizes all lectins with tandemly repeated carbohydrate recognition domains into nine distinct folding classes associated with specific biological functions. Our findings provide a comprehensive description and analysis of tandem-repeat lectins in terms of their functions and structural features. Our exploration of phyletic and functional diversity has revealed previously undocumented tandem-repeat lectins. We propose research directions aimed at enhancing our understanding of the origins of tandem-repeat lectin and fostering the development of medical and biotechnological applications, notably in the design of artificial sugars and neolectins.

Impact of Universal Use of the McGrath Videolaryngoscope as a Device for All Intubations in the Cardiac Operating Room. A Prospective Before-After VIDEOLAR-CAR Study.

OBJECTIVE: Tracheal intubation in cardiac surgery patients has a higher incidence of difficult laryngoscopic views compared with patients undergoing other types of surgery. The authors hypothesized that using the McGrath Mac videolaryngoscope as the first intubation option for cardiac surgery patients improves the percentage of patients with "easy intubation" compared with using a direct Macintosh laryngoscope. DESIGN: A prospective, observational, before-after study. SETTING: At a tertiary-care hospital. PARTICIPANTS: One thousand one hundred nine patients undergoing cardiac surgery. INTERVENTION: Consecutive patients undergoing cardiac surgery were intubated using, as the first option, a Macintosh laryngoscope (preinterventional phase) or a McGrath Mac videolaryngoscope (interventional phase). MEASUREMENTS AND MAIN RESULTS: The main objective was to assess whether the use of the McGrath videolaryngoscope, as the first intubation option, improves the percentage of patients with "easy intubation," defined as successful intubation on the first attempt, modified Cormack-Lehane grades of I or IIa, and the absence of the need for adjuvant airway devices. A total of 1,109 patients were included, 801 in the noninterventional phase and 308 in the interventional phase. The incidence of "easy intubation" was 93% in the interventional phase versus 78% in the noninterventional phase (p < 0.001). First-success-rate intubation was higher in the interventional phase (304/308; 98.7%) compared with the noninterventional phase (754/801, 94.1%; p = 0.005). Intubation in the interventional phase showed decreases in the incidence of difficult laryngoscopy (12/308 [3.9%] v 157/801 [19.6%]; p < 0.001), as well as moderate or difficult intubation (5/308 [1.6%] v 57/801 [7.1%]; p < 0.001). CONCLUSIONS: The use of the McGrath videolaryngoscope as the first intubation option for tracheal intubation in cardiac surgery improves the percentage of patients with "easy" intubation," increasing glottic view and first-success-rate intubation and decreasing the incidence of moderate or difficult intubation.

An isolated bioinductive repair vs. sutured repair for full-thickness rotator cuff tears: 2-year results of a double blinded, randomized controlled trial.

BACKGROUND: Partial-thickness rotator cuff tears treated with an isolated bioinductive repair (IBR) in lieu of a completion-and-repair have shown complete healing. This treatment option is afforded by the remaining tendon's structural integrity, which is similar to that present in small/medium full-thickness tears (FTTs) when the rotator cable remains intact. This randomized controlled trial (RCT) investigated whether an IBR for small/medium FTTs resulted in superior healing and patient-reported outcomes (PROs) compared with a sutured repair. METHODS: This prospective, double blinded (patients and outcome assessors), single-center RCT enrolled patients ≥18 years with a small/medium (≤2.5cm) full thickness supraspinatus tear and intact rotator cable. Patients were randomized and blinded to arthroscopic transosseous-equivalent repair (control, n = 30) or IBR (n = 30). The primary outcome was tendon quality on biopsy at 6 months. Secondary outcomes were PROs (American Shoulder and Elbow Surgeons [ASES], Constant-Murley Shoulder [CMS], and pain visual analogue scale scores) and tendon thickness and healing measured via MRI at 6, 12, and 24 months; satisfaction at 12 and 24 months; and time to return to work. RESULTS: Baseline demographic, tear, and surgical characteristics were comparable between the groups (IBR: mean age, 54.2 years, 14 male; control: mean age, 56.4 years, 16 male). Measured via 6 month biopsy, highly organized, parallel bundles of collagen, without inflammation, were present in all IBR patients, whereas poorly organized, non-parallel collagen fibers were present in 24/30 (80%) of control patients (P < .0001), with 28/30 having minimal to mild inflammation. The increase in tendon thickness measured via MRI at 6 months from baseline was greater in the IBR group (2.0 mm) than in the control group (0.8 mm) (P < .0001). All IBR patients had 100% healing on MRI at 12 and 24 months. Compared with the control group, the IBR group had higher ASES and CMS scores at each evaluation, less pain at 6 and 12 months, and greater satisfaction at 12 and 24 months (P < .0003). The IBR group returned to work significantly faster (median 90 days [IQR, 25] vs. median 163.5 days [IQR, 24]; P < .0001) than the control group. CONCLUSION: Compared with a sutured repair, the IBR treatment resulted in superior tendon quality, patient outcomes, satisfaction, and return to work. The IBR enabled a robust healing response evident through MRI and biopsy evaluation, demonstrating superior tendon quality and healing.

Conformational Changes and ATP Hydrolysis in Zika Helicase: The Molecular Basis of a Biomolecular Motor Unveiled by Multiscale Simulations.

We computationally study the Zika NS3 helicase, a biological motor, using ATP hydrolysis energy for nucleic acid remodeling. Through molecular mechanics and hybrid quantum mechanics/molecular mechanics simulations, we explore the conformational landscape of motif V, a conserved loop connecting the active sites for ATP hydrolysis and nucleic acid binding. ATP hydrolysis, initiated by a meta-phosphate group formation, involves the nucleophilic attack of a water molecule activated by Glu286 proton abstraction. Motif V hydrogen bonds to this water via the Gly415 backbone NH group, assisting hydrolysis. Posthydrolysis, free energy is released when the inorganic phosphate moves away from the coordination shell of the magnesium ion, inducing a significant shift in the conformational landscape of motif V to establish a hydrogen bond between the Gly415 NH group and Glu285. According to our simulations, the Zika NS3 helicase acts as a ratchet biological motor with motif V transitions steered by Gly415's γ-phosphate sensing in the ATPase site.

Structural and functional analysis of a tandem repeat galacturonic acid-binding lectin from the sea hare Aplysia californica.

A d-galacturonic acid-specific lectin, named AcL, was purified from the sea hare Aplysia californica by galactose-agarose affinity chromatography. AcL has a molecular mass of 27.5 kDa determined by MALDI-TOF mass spectrometry. This lectin shows a good affinity for d-galacturonic acid and a lower affinity for galactosides: raffinose, melibiose, α and ß-lactose, and d-galactose. We determined the amino acid sequence of AcL by trypsin digestion and subsequent peptide analysis by mass spectrometry, resulting in a 238 amino acid protein with a theoretical molecular mass of 26.4 kDa. The difference between the theoretical and experimental values can be attributed to post-translational modifications. Thiol-disulfide quantification discerned five disulfide bonds and three free cysteines. The structure of Acl is mainly comprised of beta sheets, determined by circular dichroism, and predicted with AlphaFold. Theoretical models depict three nearly identical tandem domains consisting of two beta sheets each. From docking analysis, we identified AcL glycan-binding sites as multiple conserved motifs in each domain. Furthermore, phylogenetic analysis based on its structure and sequence showed that AcL and its closest homologues (GalULs) form a clear monophyletic group, distinct from other glycan-binding proteins with a jelly-roll fold: lectins of types F and H. GalULs possess four conserved sequence regions that distinguish them and are either ligand-binding motifs or stabilizing network hubs. We suggest that this new family should be referred to as GalUL or D-type, following the traditional naming of lectins; D standing for depilans, the epithet for the species (Aplysia depilans) from which a lectin of this family was first isolated and described.

[Critical patients COVID-19 has changed the management and outcomes in the ICU after 1 year of the pandemic? A multicenter, prospective, observational study]. / Pacientes críticos COVID-19. ¿Han variado el manejo y los resultados en la UCI tras un año de pandemia? Estudio multicéntrico, prospectivo, observacional.

Objective: To compare the clinical characteristics, treatments, and evolution of critical patients with COVID-19 pneumonia treated in intensive care units (ICU) after one year of pandemic. Methodology: Multicenter, prospective study, which included critical COVID-19 patients in 9 ICUs in northwestern Spain. The clinical characteristics, treatments, and evolution of patients admitted to the ICU during the months of March-April 2020 (period 1) were compared with patients admitted in January-February 2021 (period 2). Results: 337 patients were included (98 in period 1 and 239 in period 2). In period 2, fewer patients required invasive mechanical ventilation (IMV) (65% vs. 84%, P < .001), using high-flow nasal cannulas (CNAF) more frequently (70% vs. 7%, P < .001), ventilation non-invasive mechanical (NIMV) (40% vs. 14%, P < .001), corticosteroids (100% vs. 96%, P = .007) and prone position in both awake (42% vs. 28%, P = .012), and intubated patients (67% vs. 54%, P = .034). The days of IMV, ICU stay and hospital stay were lower in period 2. Mortality was similar in the two periods studied (16% vs. 17%). Conclusions: After one year of pandemic, we observed that in patients admitted to the ICU, CNAF, NIMV, use of the prone position, and corticosteroids have been used more frequently, reducing the number of patients in IMV, and the length of stay in the ICU and hospital stay. Mortality was similar in the two study periods.

On-Surface Synthesis and Characterization of a High-Spin Aza-[5]-Triangulene.

Triangulenes are a class of open-shell triangular graphene flakes with total spin increasing with their size. In the last years, on-surface-synthesis strategies have permitted fabricating and engineering triangulenes of various sizes and structures with atomic precision. However, direct proof of the increasing total spin with their size remains elusive. In this work, we report the combined in-solution and on-surface synthesis of a large nitrogen-doped triangulene (aza-[5]-triangulene) on a Au(111) surface, and the detection of its high-spin ground state. Bond-resolved scanning tunneling microscopy images uncovered radical states distributed along the zigzag edges, which were detected as weak zero-bias resonances in scanning tunneling spectra. These spectral features reveal the partial Kondo screening of a high-spin state. Through a combination of several simulation tools, we find that the observed distribution of radical states is explained by a quintet ground state (S=2), instead of the quartet state (S=3/2) expected for the neutral species. This confirms that electron transfer to the metal substrate raises the spin of the ground state. We further provide a qualitative description of the change of (anti)aromaticity introduced by N-substitution, and its role in the charge stabilization on a surface, resulting in an S=2 aza-triangulene on Au(111).

Structural and evolutionary insights into the multidomain galectin from the red abalone Haliotis rufescens with specificity for sulfated glycans.

Galectins are an evolutionarily ancient family of lectins characterized by their affinity for ß-galactosides and a conserved binding site in the carbohydrate recognition domain (CRD). These lectins are involved in multiple physiological functions, including the recognition of glycans on the surface of viruses and bacteria. This feature supports their role in innate immune responses in marine mollusks. Here, we identified and characterized a galectin, from the mollusk Haliotis rufescens (named HrGal), with four CRDs that belong to the tandem-repeat type. HrGal was purified by affinity chromatography in a galactose-agarose resin and exhibited a molecular mass of 64.11 kDa determined by MALDI-TOF mass spectrometry. The identity of HrGal was verified by sequencing, confirming that it is a 555 amino acid protein with a mass of 63.86 kDa. This protein corresponds to a galectin reported in GenBank with accession number AHX26603. HrGal is stable in the presence of urea, reducing agents, and ions such as Cu2+ and Zn2+. The recombinant galectin (rHrGal) was purified from inclusion bodies in the presence of these ions. A theoretical model obtained with the AlphaFold server exhibits four non-identical CRDs, with a ß sandwich folding and the representative motifs for binding ß-galactosides. This allows us to classify HrGal within the tandem repeat galectin family. On the basis of a phylogenetic analysis, we found that the mollusk sequences form a monophyletic group of tetradomain galectins unrelated to vertebrate galectins. HrGal showed specificity for galactosides and glucosides but only the sulfated sugars heparin and ι-carrageenan inhibited its hemagglutinating activity with a minimum inhibitory concentration of 4 mM and 6.25 X 10-5% respectively. The position of the sulfate groups seemed crucial for binding, both by carrageenans and heparin.

Multitarget drugs as potential therapeutic agents for alzheimer's disease. A new family of 5-substituted indazole derivatives as cholinergic and BACE1 inhibitors.

Multitarget drugs are a promising therapeutic approach against Alzheimer's disease. In this work, a new family of 5-substituted indazole derivatives with a multitarget profile including cholinesterase and BACE1 inhibition is described. Thus, the synthesis and evaluation of a new class of 5-substituted indazoles has been performed. Pharmacological evaluation includes in vitro inhibitory assays on AChE/BuChE and BACE1 enzymes. Also, the corresponding competition studies on BuChE were carried out. Additionally, antioxidant properties have been calculated from ORAC assays. Furthermore, studies of anti-inflammatory properties on Raw 264.7 cells and neuroprotective effects in human neuroblastoma SH-SY5Y cells have been performed. The results of pharmacological tests have shown that some of these 5-substituted indazole derivatives 1-4 and 6 behave as AChE/BuChE and BACE1 inhibitors, simultaneously. In addition, some indazole derivatives showed anti-inflammatory (3, 6) and neuroprotective (1-4 and 6) effects against Aß-induced cell death in human neuroblastoma SH-SY5Y cells with antioxidant properties.

Effectiveness and safety of erenumab and galcanezumab in the prevention of chronic and episodic migraine: A retrospective cohort study.

WHAT IS KNOWN AND OBJECTIVE?: Erenumab and galcanezumab have shown great results for migraine prevention. However, strict inclusion criteria, absence of concomitant medication and selective outcome report of clinical trials may sometimes be barely representative of the real-world daily practice. Therefore, this study was designed to evaluate effectiveness and safety of these two monoclonal antibodies targeting calcitonin gene-related peptide in real-world patients. METHODS: This observational, retrospective study evaluated the effectiveness and safety of erenumab 140 mg and galcanezumab 120 mg in 142 real-world patients who had previously not responded to three well-established pharmacological alternatives for migraine prevention. To do so, a combination of objective parameters (monthly headache days and acute migraine-specific medication days) and subjective measurements (Migraine Disability Assessment questionnaire, Headache Impact Test and Visual Analogue Scale), validated for clinical research in migraine, were assessed during clinical interview. RESULTS AND DISCUSSION: Findings here reported show that erenumab and galcanezumab reduced monthly headache days, acute migraine specific medication days per month, Headache Impact Test score, Migraine Disability Assessment Test score and Visual Analogue Scale score after 3 and 6 doses (p < 0.01). Additionally, more than 25% of the patients enrolled in the study experienced a reduction by a half in monthly headache days, and more than 50% of the patients also reported a reduction by a half in the number of migraine specific medication days. Both treatments exhibited a great safety profile, rarely leading to discontinuation because of poor tolerance. WHAT IS NEW AND CONCLUSIONS?: Altogether, these results support previous real-life studies regarding effectiveness and safety and provide an interesting insight in how these preventive therapies are also effective in patients diagnosed with difficult to treat migraine who have previously failed, at least, three different drug classes stablished by current neurology guidelines for migraine prevention. Moreover, these data may suggest that erenumab and galcanezumab are able to not only diminish frequency, but also migraine intensity, and that it should be also considered as an effectiveness measure in line with other authors suggestion.

Prevalence of Glucose-6-Phosphate Dehydrogenase Deficiency in Newborns in Northeast Mexico.

OBJECTIVE: Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is the most common enzymatic disease worldwide and the prevalence is not well established because of the lack of screening. This study aimed to estimate the prevalence of G6PDd in a Hispanic population from Northeast Mexico. STUDY DESIGN: In this retrospective study, a database was used to analyze the G6PDd in neonates included in the expanded newborn metabolic screening of inherited metabolic disorders during a period of 4 years through the GSP Neonatal G6 kit (PerkinElmer). RESULTS: Among 96,152 (48,462 male) neonates screened for G6PD enzyme activity, a total of 566 (0.58%) cases were deficient for G6PD. Of those 566 patients, 469 (82.8%) attended the second test and the other 97 (17.2%) patients were lost. Of those 469 who did attend, 384 (81.9%) neonates were deficient in the second test and 85 (18.1%) were normal. With the data collected, 384 neonates were confirmed with G6PDd, 348 (88.6%) were male and 36 (11.4%) patients were female. The calculated prevalence for this population was 0.72 cases per 100 male newborns. CONCLUSION: The prevalence of G6PDd in the Northeastern Mexican population is high. Since migration is increasing in the United States, pediatricians should be aware of the need to search for G6PDd in newborns and the wide clinical manifestations they can present. KEY POINTS: · The calculated prevalence of glucose-6-phosphate dehydrogenase deficiency in Northeast Mexico is 3.99 cases per 1,000 newborns.. · Glucose-6-phosphate dehydrogenase deficiency screenings should be included in all newborn metabolic screenings.. · Glucose-6-phosphate dehydrogenase deficiency is a common erythroenzymopathy that must be addressed as a public health concern. To anticipate clinical complications, target population monitoring is required..

Identification of Microcrustaceans as Potential Bioindicators of Arsenic in Tropical Water Bodies.

We investigated microcrustaceans inhabiting arsenic contaminated and non-contaminated freshwater to identify potential bioindicators of arsenic contamination in the tropical freshwater of Matehuala in northern Mexico. We collected water, sediment, and zooplankton, at five sampling points during three sampling campaigns. We determined water temperature, pH, electrical conductivity, dissolved oxygen, alkalinity, salinity, and total arsenic concentration in water. Additionally, we determined total arsenic and arsenic speciation in sediment samples. We identified microcrustaceans and determined abundance, richness, and Shannon Index. We also investigated relationships and correlations between physiochemical and ecological variables. Results showed that arsenic concentrations in freshwater ranged from 0.001 to 53.23 mg/L, while total arsenic in sediments ranged from 10.37 to 2472.84 mg/kg as As + 5. Six microcrustacean species were found in highly and moderately contaminated water (Latonopsis australis, Eucyclops chihuahuensis, Acanthocyclops americanus, Pleuroxus (Picripleuroxus) quasidenticulatus, Macrocyclops albidus, and Paracyclops chiltoni), while five species were found in arsenic-free water (Simocephalus punctatus, Alona glabra, Eucyclops leptacanthus, M. albidus, and P. quasidenticulatus). An inverse relationship was observed between microcrustacean richness and arsenic. However, the scope of the data did not allow for a strong and significant correlation. Nevertheless, among the species inhabiting As-free water, S. punctatus showed potential to be further tested as a bioindicator of As contamination in Matehuala. Identification of potential bioindicators could help monitor water quality and increase understanding of the incorporation and toxicity of As in freshwater-sensitive and freshwater-metallotolerant microcrustaceans, which, in turn, might help us to understand As incorporation in the food web.

Simple anthropometry-based calculations to monitor body composition in athletes: Scoping review and reference values.

BACKGROUND: Kinanthropometry offers to exercise and health professionals a standardized procedure of acquiring surface anatomical measurements that might be used to track changes in body composition. AIM: To describe simple anthropometric indices to monitor body composition changes in amateur and elite athletes, and to provide reference values during the competition phase. METHODS: A search of articles indexed in PubMed/MEDLINE, ScienceDirect, Cochrane, and SciELO databases using the string body composition AND (anthropometric OR skinfolds OR circumferences OR girth OR estimation equation) AND "body fat". Inclusion criteria were: quantitative and/or qualitative research published between 2009 and 2020, written in English or Spanish, reporting simple anthropometric indices that included skinfolds, girths, or basic measures in amateur and elite athletes. RESULTS: A total of 51 studies (Price's index = 66.4%) met all the inclusion criteria and were included in this scoping review. Contrary to the frequent practice, the use of a regression equation might not be accurate to evaluate body composition. To avoid this, anthropometrists should base their analysis on the absolute values of the sum of skinfolds (∑S) and related variables, such as skinfold-corrected girths and lean mass index. While not definitive, because further research is required, the practical recommendations and updated reference values in competition phase provided by this review would contribute to the accurate identification of body composition changes. CONCLUSIONS: ∑S and lean mass index have been shown to be valid for monitoring changes in fat mass and fat-free mass, respectively. More research is needed to derive the lean mass index-specific coefficient for each sports population.

On-DNA Palladium-Catalyzed Hydrogenation-like Reaction Suitable for DNA-Encoded Library Synthesis.

Herein we describe a method to orthogonally remove on-DNA N-Cbz, N-Alloc, N-Allyl, O-Bn, and O-Allyl protecting groups in the presence of other common protecting groups to afford free amines and carboxylic acids, respectively. The developed method uses NaBH4 as the source of hydrogen in the presence of Pd(OAc)2 under DNA aqueous conditions. In addition, under the developed conditions we were able to successfully hydrogenate triple and double bonds to totally saturated compounds. Furthermore, we introduce a new alternative procedure to reduce azides and aromatic nitro compounds to primary amines.

Effectiveness of Prone Positioning in Nonintubated Intensive Care Unit Patients With Moderate to Severe Acute Respiratory Distress Syndrome by Coronavirus Disease 2019.

BACKGROUND: In the treatment for severe acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19), the World Health Organization (WHO) recommends prone positioning (PP) during mechanical ventilation for periods of 12-16 h/d to potentially improve oxygenation and survival. In this prospective observational study, we evaluated the ability of long PP sessions to improve oxygenation in awake intensive care unit (ICU) patients with moderate or severe ARDS due to COVID-19. METHODS: The study was approved by the ethics committee of Galicia (code No. 2020-188), and all patients provided informed consent. In this case series, awake patients with moderate or severe ARDS by COVID-19 admitted to the ICU at University Hospital of Santiago from March 21 to April 5, 2020 were prospectively analyzed. Patients were instructed to remain in PP as long as possible until the patient felt too tired to maintain that position. Light sedation was administered with dexmedetomidine. The following information was collected: number and duration of PP sessions; tissue O2 saturation (StO2) and blood gases before, during, and following a PP session; need of mechanical ventilation; duration of ICU admission; and ICU outcome. Linear mixed-effects models (LMM) were fit to estimate changes from baseline with a random effect for patient. RESULTS: Seven patients with moderate or severe ARDS by COVID-19 were included. All patients received at least 1 PP session. A total of 16 PP sessions were performed in the 7 patients during the period study. The median duration of PP sessions was 10 hours. Dexmedetomidine was used in all PP sessions. Oxygenation increased in all 16 sessions performed in the 7 patients. The ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FIO2) significantly increased during PP (change from baseline 110 with 97.5% confidence interval [CI], 19-202) and, after PP, albeit not significantly (change from baseline 38 with 97.5% CI, -9.2 to 85) compared with previous supine position. Similarly, tissue oxygenation underwent a small improvement during PP (change from baseline 2.6% with 97.5% CI, 0.69-4.6) without significant changes after PP. Two patients required intubation. All patients were discharged from the ICU. CONCLUSIONS: We found that PP improved oxygenation in ICU patients with COVID-19 and moderate or severe ARDS. PP was relatively well tolerated in our patients and may be a simple strategy to improve oxygenation trying to reduce the number of patients in mechanical ventilation and the length of stay in the ICU, especially in COVID-19 pandemic.

RETROPUPILLARY IRIS-CLAW INTRAOCULAR LENS AND PARS PLANA VITRECTOMY IN APHAKIA MANAGEMENT: A National Multicenter Audit.

PURPOSE: To evaluate the outcomes and safety of retropupillary iris-claw intraocular lens implantation and associated pars plana vitrectomy. METHODS: Multicenter, national audit of 325 eyes (325 patients). Demographics, surgical details, and complications are described. Visual acuity, intraocular pressure, and central retinal thickness assessed by optical coherence tomography were collected at 1, 3, 6, and 12 months after surgery. Kaplan-Meier curves were created to assess the cumulative probability of postoperative visual acuity and intraocular pressure levels, macular edema development, and corneal decompensation. RESULTS: The cumulative probability of the final visual acuity ≤0.3 logarithm of the minimum angle of resolution (≥20/40 Snellen) was 75.6% at 12-month follow-up. The probability of intraocular pressure >21, ≥25, and ≥30 mmHg was 48.1%, 33.1%, and 19.0%, and the probability of intraocular pressure-lowering drops was 50.9% at 12 months. Glaucoma surgery was required in 4.3% of the eyes (14/325). The cumulative probability of macular edema was 20.5% at 12 months and was greater in complicated cataract surgery than in intraocular lens-luxation eyes (26% vs. 16.7%, P = 0.04). Corneal transplantation was required in 2.8% of the eyes (9/325). CONCLUSION: This study on 325 eyes with aphakia or intraocular lens dislocation managed with the retropupillary iris-claw intraocular lens technique provides clinical outcomes in a real-world scenario, reporting relevant data for patient counseling and preoperative discussions.

Sarcopenia: Etiology, Nutritional Approaches, and miRNAs.

Sarcopenia, an age-related decline in skeletal muscle mass and function, dramatically affects the quality of life. Although there is a consensus that sarcopenia is a multifactorial syndrome, the etiology and underlying mechanisms are not yet delineated. Moreover, research about nutritional interventions to prevent the development of sarcopenia is mainly focused on the amount and quality of protein intake. The impact of several nutrition strategies that consider timing of food intake, anti-inflammatory nutrients, metabolic control, and the role of mitochondrial function on the progression of sarcopenia is not fully understood. This narrative review summarizes the metabolic background of this phenomenon and proposes an integral nutritional approach (including dietary supplements such as creatine monohydrate) to target potential molecular pathways that may affect reduce or ameliorate the adverse effects of sarcopenia. Lastly, miRNAs, in particular those produced by skeletal muscle (MyomiR), might represent a valid tool to evaluate sarcopenia progression as a potential rapid and early biomarker for diagnosis and characterization.

Iris-Claw Intraocular Lens: Anterior Chamber or Retropupillary Implantation? A Systematic Review and Meta-Analysis.

Background and Objectives: Iris-claw intraocular lens (ICIOL) could be implanted in the anterior chamber (AC) or retropupillary (RP) in eyes lacking capsular and/or zonular support. Several studies have focused on comparing the efficacy and complications of these two techniques and we designed this research to review the published literatures. Materials and Methods: Peer-reviewed studies were collected through network databases (PubMed, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) and analyzed. The primary outcome was the standardized mean differences (SMDs) of pre- and post-operative corrected distant visual acuity (CDVA). The secondary outcome was the SMDs of pre- and post-operative intraocular pressure (IOP), endothelial cell counts (ECC), and the odds ratios (ORs) of post-operative IOP elevation and cystoid macular edema (CME). Comprehensive Meta-Analysis software was utilized to conduct statistical analysis. Results: Six studies (one randomized controlled trial and five retrospective case series) were relevant and included a total of 516 eyes (255 and 261 eyes in the AC ICIOL and RP ICIOL groups, respectively). The quantitative analysis showed no significant differences in CDVA (SMD: 0.164, 95% confidence interval (CI): -0.171 to 0.500), ECC (SMD: -0.011, 95% CI: -0.195 to 0.173), and IOP elevation events (OR: 0.797, 95% CI: 0.459 to 1.383). Lesser IOP reduction (SMD: 0.257, 95%CI: 0.023 to 0.490) and a relative increase in the incidence of CME (OR:2.315, 95% CI: 0.950 to 5.637) were observed in the AC ICIOL group compared with RP ICIOL group. Conclusions: Our meta-analysis indicated that AC and RP ICIOL seem to have equivalent visual outcomes. RP ICIOL may perform slightly better with more IOP reduction and lesser CME. More randomized controlled trials, which have higher patient participation and more outcomes are needed to confirm our conclusions.

Gender differences in the effects of cannabidiol on ethanol binge drinking in mice.

The purpose of this study was to explore the effects of cannabidiol (CBD) on binge drinking and evaluate potential gender-related differences. To this aim, male and female C57BL/6J mice (n = 60 per sex) were exposed to the drinking in the dark (DID) model for 4 weeks (DID-1 to DID-4). Dose-response effects of CBD on the ethanol intake were tested by acute (day-4 of DID-3) or repeated administration (day-1 to 4 of DID-4) (experiment 1: CBD 15, 30, and 60 mg/kg, i.p.; experiment 2: CBD 90 mg/kg, i.p.). Finally, we analyzed the relative gene expression of tyrosine hydroxylase (TH) and µ-opioid receptor (OPRM1) and cannabinoid CB1 receptor (CB1 r) in the ventral tegmental area (VTA) and in the nucleus accumbens (NAc), respectively, by real-time quantitative PCR. Females exhibited higher ethanol intake during each DID session. Interestingly, females also showed higher expression of TH and OPRM1, without any difference in CB1 r. Only the acute administration of CBD at the highest dose (90 mg/kg) reduced significantly ethanol consumption in both sexes. Chronic CBD administration (30, 60 and 90 mg/kg) reduced ethanol intake in males, whereas in females a significant reduction was only achieved with the highest dose (90 mg/kg). Repeated administration with CBD (60 mg/kg) significantly reduced TH and OPRM1 in males. In addition, CBD (30 and 60 mg/kg) significantly reduced CB1 r in males. No effect was observed in females. Taken together, these findings suggest that CBD may be of interest for treating binge-drinking patterns and that gender-related difference may affect the treatment outcome.

Does glitazone treatment have a role on the prevention of Parkinson's disease in adult diabetic population? A systematic review.

Lately, focus on the relation between Parkinson's disease (PD) and Diabetes has risen greatly, as neuroprotective properties have been attributed to insulin use. Several studies have assessed the effect of glitazones, an insulin-sensitizing agent, in diabetic population on PD future risk. However, reports on the effect of their use have been heterogeneous. We aimed to synthesize the available scientific evidence which assesses the effect of glitazone use in type 2 diabetes patients on PD incidence. A systematic review was performed on multiple electronic databases. Considered for inclusion were studies that assessed the incidence of PD in type 2 diabetes glitazone users. Two reviewers worked independently and in duplicate to assess all studies, extract information and assess the methodological quality in each included study. Four high quality retrospective cohorts fulfilled inclusion criteria. Comparison groups varied across studies. In each study, incidence of PD was lower in glitazone-exposed patients compared to their respective comparison group. Pooled analysis showed lesser risk of PD in ever versus never glitazone users (RR 0.75 [95% C.I. 0.67-0.85; p < .0001; I2 = 0]). Our pooled analysis showed lesser risk of PD in glitazone versus non glitazone users, however, we advise to take results with caution since results are non-adjusted to possible confounding variables, furthermore, different glitazone-exposure time, follow up and comparison groups are aspects that also need to be pointed out. More clinical research focused on glitazone use and its relation with PD is needed, as this could result in new potential treatment modalities.