Unravelling the analgesic effects of perioperative magnesium in general abdominal surgery: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Prior research has established the effectiveness of magnesium in relieving postoperative pain. This article aims to evaluate magnesium sulfate for perioperative analgesia in adults undergoing general abdominal surgery under general anesthesia. OBJECTIVE: The primary aim was to assess pain scores at 6 and 24 hours postoperatively in patients receiving magnesium sulfate vs. the control group. Secondary outcomes were postoperative opioid consumption, perioperative complications, and time to rescue analgesia. METHODS: A comprehensive database search identified studies comparing magnesium sulfate with control in adults undergoing general anesthesia for general abdominal surgery. Using random-effects models, data were presented as mean ± Standard Deviation (SD) or Odds Ratios (OR) with corresponding 95% Confidence Intervals (95% CI). A two-sided p-value < 0.05 was considered statistically significant. RESULTS: In total, 31 studies involving 1762 participants met the inclusion criteria. The magnesium group showed significantly lower postoperative pain scores at both early (within six hours) and late (up to 24 hours) time points compared to the control group. The early mean score was 3.1 ± 1.4 vs. 4.2 ± 2.3, and the late mean score was 2.3 ± 1.1 vs. 2.7 ± 1.5, resulting in an overall Mean Difference (MD) of -0.72; 95% CI -0.99, -0.44; p < 0.00001. The magnesium group was associated with lower rates of postoperative opioid consumption and shivering and had a longer time to first analgesia administration compared to the saline control group. CONCLUSION: Magnesium sulfate administration was linked to reduced postoperative pain and opioid consumption following general abdominal surgery.

Comparison of Different Weight Scalars to Dose Sugammadex for the Reversal of Neuromuscular Blockade in Morbidly Obese Patients: A Systematic Review.

This systematic review was conducted to evaluate the optimal weight scalar to dose sugammadex in a morbidly obese (MO) patient population (BMI≥40 kg/m2). The primary outcome was recovery time from moderate neuromuscular blockade (NMB) or deep NMB. Secondary outcomes included time to extubation and incidence of postoperative residual curarization (PORC). Eight randomized controlled trials (RCTs) involving 645 participants were included. The different dose scalars included were total body weight (TBW), ideal body weight (IBW), 20% corrected body weight (CBW) and 40% CBW). A dose of 2 mg/kg of sugammadex based on 40% CBW and a 4 mg/kg dose of sugammadex based on 40% CBW provide a reliable and timely reversal of moderate and deep NMB respectively in the MO patients.

Three-year clinical outcome of XEN45 Gel Stent implantation versus trabeculectomy in patients with open angle glaucoma.

OBJECTIVE: To reliably compare the three-year clinical outcome and safety of XEN45 Gel Stent implantation (XEN) vs. trabeculectomy (TRAB) in patients with glaucoma. SUBJECT/METHODS: We conducted a retrospective cohort study with patients with primary open angle or pseudoexfoliation glaucoma with uncontrolled intraocular pressure (IOP) undergoing XEN or TRAB at the Innsbruck University Clinic of Ophthalmology and Optometry, Austria and analysed changes in IOP, numbers of IOP-lowering medications, and complete surgical success (i.e., IOP ≤ 18 mmHg, ≥20% IOP reduction and not requiring IOP-lowering medication) up to 36 months postoperatively. RESULTS: Between 2013 and 2019, we performed XEN Gel Stent implantation in 58 eyes and trabeculectomy in 84 eyes. From baseline to 36 months, mean IOP decreased from 23.4 to 13.8 mmHg (mean reduction 35%, 95% confidence interval 23-48%, p < 0.001) in the XEN group and from 25.1 to 11.2 mmHg (mean reduction 50%, 41-60%, p < 0.001) in the TRAB group. TRAB provided higher IOP reduction than XEN Gel Stent implantation at 12, 24, and 36 months (all p < 0.05). In XEN versus TRAB, IOP-lowering medication was required by 98.3% vs. 97.6% before surgery (p = 0.781), differed significantly at month 12 (43.2% vs. 2.0%, p < 0.001)but not at month 24 or 36. Complete surgical success was achieved in 40.0% vs. 62.8% at month 24 (adjusted odds ratio 2.70; 1.04-7.00, p = 0.040) and 27.3% vs. 56.8% at month 36 (4.36; 1.25-15.18, p = 0.021). CONCLUSION: Compared to XEN, TRAB was associated with lower intraocular pressure, less IOP-lowering medication, and higher probability of achieving complete surgical success over a 36-month follow-up period.

The impact of music, play, and pet therapies in managing pain and anxiety in paediatric patients in hospital: a rapid systematic review.

Background: Hospitalized children face pain and anxiety associated with the environment and procedures. Objective: This review aimed to assess the impact of music, play, pet and art therapies on pain and anxiety in hospitalized paediatric patients. RCTs assessing the impact of music, play, pet, and/or art therapies on pain and/or anxiety in hospitalized paediatric patients were eligible. Methods: Database searching and citation screening was completed to identify studies. A narrative synthesis was used to summarize study findings and certainty of evidence was assessed using GRADE. Of the 761 documents identified, 29 were included spanning music (n = 15), play (n = 12), and pet (n = 3) therapies. Results: A high certainty of evidence supported play in reducing pain and moderate certainty for music and pet. A moderate certainty of evidence supported music and play in reducing anxiety. Conclusion: Complementary therapies utilized alongside conventional medical treatment may mitigate pain and anxiety in hospitalized paediatric patients.

Protocol for a systematic review on effective patient positioning for rapid sequence intubation.

INTRODUCTION: Rapid sequence intubation (RSI) is an advanced airway technique to perform endotracheal intubation in patients at high risk of aspiration. Although RSI is recognised as a life-saving technique and performed by many physicians in various settings (emergency departments, intensive care units), there is still a lack of consensus on various features of the procedure, most notably patient positioning. Previously, experts have commented on the unique drawbacks and benefits of various positions and studies have been published comparing patient positions and how it can affect endotracheal intubation in the context of RSI. The purpose of this systematic review is to compile the existing evidence to understand and compare how different patient positions can potentially affect the success of RSI. METHODS AND ANALYSIS: We will use MEDLINE, EMBASE and the Cochrane Library to source studies from 1946 to 2021 that evaluate the impact of patient positioning on endotracheal intubation in the context of RSI. We will include randomised control trials, case-control studies, prospective/retrospective cohort studies and mannequin simulation studies for consideration in this systematic review. Subsequently, we will generate a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram to display how we selected our final studies for inclusion in the review. Two independent reviewers will complete the study screening, selection and extraction, with a third reviewer available to address any conflicts. The reviewers will extract this data in accordance with our outcomes of interest and display it in a table format to highlight patient-relevant outcomes and difficulty airway management outcomes. We will use the Risk of Bias tool and the Newcastle-Ottawa Scale to assess included studies for bias. ETHICS AND DISSEMINATION: This systematic review does not require ethics approval, as all patient-centred data will be reported from published studies. PROSPERO REGISTRATION NUMBER: CRD42022289773.

Yoga as medicine: Understanding Bhutanese refugee perspectives on health and healthcare.

Bhutanese refugees in the U.S. often struggle to access culturally competent health treatment. Addressing this problem requires understanding how refugees perceive their health and healthcare needs. Since 2015, a community agency has implemented community-based, peer-led support groups for Bhutanese refugees, with 17 groups in 2018-2019. This study describes the agency's quality assurance evaluation through group leader feedback, observation reports, and focus groups. The results of 46 quality assurance documents show that this group of Bhutanese refugees perceive their health through the mind-body connection, viewing physical and mental health as linked and supported by yoga, mindfulness, exercise, nutrition, and creative expression.

A functional connectome phenotyping dataset including cognitive state and personality measures.

The dataset enables exploration of higher-order cognitive faculties, self-generated mental experience, and personality features in relation to the intrinsic functional architecture of the brain. We provide multimodal magnetic resonance imaging (MRI) data and a broad set of state and trait phenotypic assessments: mind-wandering, personality traits, and cognitive abilities. Specifically, 194 healthy participants (between 20 and 75 years of age) filled out 31 questionnaires, performed 7 tasks, and reported 4 probes of in-scanner mind-wandering. The scanning session included four 15.5-min resting-state functional MRI runs using a multiband EPI sequence and a hig h-resolution structural scan using a 3D MP2RAGE sequence. This dataset constitutes one part of the MPI-Leipzig Mind-Brain-Body database.

BMS 493 Modulates Retinoic Acid-Induced Differentiation During Expansion of Human Hematopoietic Progenitor Cells for Islet Regeneration.

Cellular therapies are emerging as a novel treatment strategy for diabetes. Thus, the induction of endogenous islet regeneration in situ represents a feasible goal for diabetes therapy. Umbilical cord blood-derived hematopoietic progenitor cells (HPCs), isolated by high aldehyde dehydrogenase activity (ALDHhi), have previously been shown to reduce hyperglycemia after intrapancreatic (iPan) transplantation into streptozotocin (STZ)-treated nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. However, these cells are rare and require ex vivo expansion to reach clinically applicable numbers for human therapy. Therefore, we investigated whether BMS 493, an inverse retinoic acid receptor agonist, could prevent retinoic acid-induced differentiation and preserve islet regenerative functions during expansion. After 6-day expansion, BMS 493-treated cells showed a twofold increase in the number of ALDHhi cells available for transplantation compared with untreated controls. Newly expanded ALDHhi cells showed increased numbers of CD34 and CD133-positive cells, as well as a reduction in CD38 expression, a marker of hematopoietic cell differentiation. BMS 493-treated cells showed similar hematopoietic colony-forming capacity compared with untreated cells, with ALDHhi subpopulations producing more colonies than low aldehyde dehydrogenase activity subpopulations for expanded cells. To determine if the secreted proteins of these cells could augment the survival and/or proliferation of ß-cells in vitro, conditioned media (CM) from cells expanded with or without BMS 493 was added to human islet cultures. The total number of proliferating ß-cells was increased after 3- or 7-day culture with CM generated from BMS 493-treated cells. In contrast to freshly isolated ALDHhi cells, 6-day expansion with or without BMS 493 generated progeny that were unable to reduce hyperglycemia after iPan transplantation into STZ-treated NOD/SCID mice. Further strategies to reduce retinoic acid differentiation during HPC expansion is required to expand ALDHhi cells without the loss of islet regenerative functions.

A Bench-Stable, Single-Component Precatalyst for Silyl-Heck Reactions.

Studies of the silyl-Heck reaction aimed at identifying active palladium complexes have revealed a new species that is formed in situ. This complex has been identified as the palladium iodide dimer, [(JessePhos)PdI2]2, which has been found to be a competent single-component precatalyst for the silyl-Heck reaction. This complex is easily prepared and is temperature, moisture, and air stable. Additionally, this precatalyst provides higher activity and greater reproducibility compared to previous systems.

Predation risk and abiotic habitat parameters affect personality traits in extremophile populations of a neotropical fish (Poecilia vivipara).

Understanding whether and how ambient ecological conditions affect the distribution of personality types within and among populations lies at the heart of research on animal personality. Several studies have focussed on only one agent of divergent selection (or driver of plastic changes in behavior), considering either predation risk or a single abiotic ecological factor. Here, we investigated how an array of abiotic and biotic environmental factors simultaneously shape population differences in boldness, activity in an open-field test, and sociability/shoaling in the livebearing fish Poecilia vivipara from six ecologically different lagoons in southeastern Brazil. We evaluated the relative contributions of variation in predation risk, water transparency/visibility, salinity (ranging from oligo- to hypersaline), and dissolved oxygen. We also investigated the role played by environmental factors for the emergence, strength, and direction of behavioral correlations. Water transparency explained most of the behavioral variation, whereby fish from lagoons with low water transparency were significantly shyer, less active, and shoaled less than fish living under clear water conditions. When we tested additional wild-caught fish from the same lagoons after acclimating them to homogeneous laboratory conditions, population differences were largely absent, pointing toward behavioral plasticity as a mechanism underlying the observed behavioral differences. Furthermore, we found correlations between personality traits (behavioral syndromes) to vary substantially in strength and direction among populations, with no obvious associations with ecological factors (including predation risk). Altogether, our results suggest that various habitat parameters simultaneously shape the distribution of personality types, with abiotic factors playing a vital (as yet underestimated) role. Furthermore, while predation is often thought to lead to the emergence of behavioral syndromes, our data do not support this assumption.

Shared and unique patterns of phenotypic diversification along a stream gradient in two congeneric species.

Stream ecosystems show gradual variation of various selection factors, which can result in a zonation of species distributions and gradient evolution of morphological and life-history traits within species. Identifying the selective agents underlying such phenotypic evolution is challenging as different species could show shared and/or unique (species-specific) responses to components of the river gradient. We studied a stream gradient inhabited by two mosquitofishes (genus Gambusia) in the Río Grijalva basin in southern Mexico and found a patchy distribution pattern of both congeners along a stretch of 100 km, whereby one species was usually dominant at a given site. We uncovered both shared and unique patterns of diversification: some components of the stream gradient, including differences in piscine predation pressure, drove shared patterns of phenotypic divergence, especially in females. Other components of the gradient, particularly abiotic factors (max. annual temperature and temperature range) resulted in unique patterns of divergence, especially in males. Our study highlights the complexity of selective regimes in stream ecosystems. It exemplifies that even closely related, congeneric species can respond in unique ways to the same components of the river gradient and shows how both sexes can exhibit quite different patterns of divergence in multivariate phenotypic character suites.

Synthesis of Secondary Unsaturated Lactams via an Aza-Heck Reaction.

The preparation of unsaturated secondary lactams via the palladium-catalyzed cyclization of O-phenyl hydroxamates onto a pendent alkene is reported. This method provides rapid access to a broad range of lactams that are widely useful building blocks in alkaloid synthesis. Mechanistic studies support an aza-Heck-type pathway.

Direct Synthesis of Alkenyl Boronic Esters from Unfunctionalized Alkenes: A Boryl-Heck Reaction.

We report the first example of a boryl-Heck reaction using an electrophilic boron reagent. This palladium-catalyzed process allows for the conversion of terminal alkenes to trans-alkenyl boronic esters using commercially available catecholchloroborane (catBCl). In situ transesterification allows for rapid access to a variety of boronic esters, amides, and other alkenyl boron adducts.

No association of oral lichen planus and hepatitis C virus infection in central Germany.

OBJECTIVES: Co-occurrence of oral lichen planus (OLP) and chronic hepatitis C virus (HCV) infection suggests a strong association, but the relation between mucocutaneus, autoimmune lichen planus and HCV infection remains unclear. In areas with higher prevalence of HCV infection in general population, like Japan and southern Europe, 20 to 40 % of patients with OLP test positive for anti-HCV antibodies, whereas in German populations, a co-occurrence of 4.2 to 16 % was reported. MATERIAL AND METHODS: We screened 143 patients with histopathologically proven OLP for prevalence of anti-HCV antibodies. Additionally, we examined 51 anti-HCV-positive subjects with current or past HCV infection for clinical symptoms of OLP. In all patients, confirmatory diagnosis was made by the detection of HCV RNA via reverse transcription-polymerase chain reaction (RT-PCR). A randomized control group comprised 109 blood sera samples of patients without any characteristics of OLP. RESULTS: The results of all patients showed no co-occurrence in either cohort. CONCLUSION: In conclusion, no association between oral lichen planus and chronic HCV infection in our study population was found. CLINICAL RELEVANCE: Anti-HCV antibody screening in patients with confirmed oral lichen planus is not indicated routinely in central Germany.

Simplified Preparation of Trialkylvinylsilanes via the Silyl-Heck Reaction Utilizing a Second Generation Catalyst.

Recently we reported a second-generation ligand, bis(3,5-di-tert-butylphenyl)(tert-butyl)phosphine, for the preparation of allyl silanes using the silyl-Heck reaction. We now show that this new ligand also provides superior reactivity in the preparation of vinylsilanes from styrene derivatives. For the first time, this new ligand provides exceptionally high yields of trialkylvinylsilanes using a widely available palladium pre-catalyst, Pd2(dba)3. Finally, we demonstrate that this new catalyst system is able to form more highly decorated all carbon substituted vinylsilanes that have been shown to possess superior reactivity in oxidation and cross coupling reactions.

Mer tyrosine kinase promotes the survival of t(1;19)-positive acute lymphoblastic leukemia (ALL) in the central nervous system (CNS).

Patients with t(1;19)-positive acute lymphoblastic leukemia (ALL) are prone to central nervous system (CNS) relapses, and expression of the TAM (Tyro3, Axl, and Mer) receptor Mer is upregulated in these leukemias. We examined the functional role of Mer in the CNS in preclinical models and performed correlative studies in 64 t(1;19)-positive and 93 control pediatric ALL patients. ALL cells were analyzed in coculture with human glioma cells and normal rat astrocytes: CNS coculture caused quiescence and protection from methotrexate toxicity in Mer(high) ALL cell lines, which was antagonized by short hairpin RNA-mediated knockdown of Mer. Mer expression was upregulated, prosurvival Akt and mitogen-activated protein kinase signaling were activated, and secretion of the Mer ligand Galectin-3 was stimulated. Mer(high) t(1;19) primary cells caused CNS involvement to a larger extent in murine xenografts than in their Mer(low) counterparts. Leukemic cells from Mer(high) xenografts showed enhanced survival in coculture. Treatment of Mer(high) patient cells with the Mer-specific inhibitor UNC-569 in vivo delayed leukemia onset, reduced CNS infiltration, and prolonged survival of mice. Finally, a correlation between high Mer expression and CNS positivity upon initial diagnosis was observed in t(1;19) patients. Our data provide evidence that Mer is associated with survival in the CNS in t(1;19)-positive ALL, suggesting a role as a diagnostic marker and therapeutic target.

Novel bispecific antibodies increase γδ T-cell cytotoxicity against pancreatic cancer cells.

The ability of human γδ T cells from healthy donors to kill pancreatic ductal adenocarcinoma (PDAC) in vitro and in vivo in immunocompromised mice requires the addition of γδ T-cell-stimulating antigens. In this study, we demonstrate that γδ T cells isolated from patients with PDAC tumor infiltrates lyse pancreatic tumor cells after selective stimulation with phosphorylated antigens. We determined the absolute numbers of γδ T-cell subsets in patient whole blood and applied a real-time cell analyzer to measure their cytotoxic effector function over prolonged time periods. Because phosphorylated antigens did not optimally enhance γδ T-cell cytotoxicity, we designed bispecific antibodies that bind CD3 or Vγ9 on γδ T cells and Her2/neu (ERBB2) expressed by pancreatic tumor cells. Both antibodies enhanced γδ T-cell cytotoxicity with the Her2/Vγ9 antibody also selectively enhancing release of granzyme B and perforin. Supporting these observations, adoptive transfer of γδ T cells with the Her2/Vγ9 antibody reduced growth of pancreatic tumors grafted into SCID-Beige immunocompromised mice. Taken together, our results show how bispecific antibodies that selectively recruit γδ T cells to tumor antigens expressed by cancer cells illustrate the tractable use of endogenous γδ T cells for immunotherapy.

TGF-ß2 dictates disseminated tumour cell fate in target organs through TGF-ß-RIII and p38α/ß signalling.

In patients, non-proliferative disseminated tumour cells (DTCs) can persist in the bone marrow (BM) while other organs (such as lung) present growing metastasis. This suggested that the BM might be a metastasis 'restrictive soil' by encoding dormancy-inducing cues in DTCs. Here we show in a head and neck squamous cell carcinoma (HNSCC) model that strong and specific transforming growth factor-ß2 (TGF-ß2) signalling in the BM activates the MAPK p38α/ß, inducing an (ERK/p38)(low) signalling ratio. This results in induction of DEC2/SHARP1 and p27, downregulation of cyclin-dependent kinase 4 (CDK4) and dormancy of malignant DTCs. TGF-ß2-induced dormancy required TGF-ß receptor-I (TGF-ß-RI), TGF-ß-RIII and SMAD1/5 activation to induce p27. In lungs, a metastasis 'permissive soil' with low TGF-ß2 levels, DTC dormancy was short-lived and followed by metastatic growth. Importantly, systemic inhibition of TGF-ß-RI or p38α/ß activities awakened dormant DTCs, fuelling multi-organ metastasis. Our work reveals a 'seed and soil' mechanism where TGF-ß2 and TGF-ß-RIII signalling through p38α/ß regulates DTC dormancy and defines restrictive (BM) and permissive (lung) microenvironments for HNSCC metastasis.