TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti-PD-1 tumor immunotherapy.

The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti-programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering receptor on myeloid cells 2 (TREM2) attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti-PD-1. Here, we found that anti-PD-1 treatment combined with TREM2 deficiency in mice induces proinflammatory programs in intestinal macrophages and a concomitant expansion of Ruminococcus gnavus in the gut microbiota. Gavage of wild-type mice with R. gnavus enhanced anti-PD-1-mediated tumor elimination, recapitulating the effect occurring in the absence of TREM2. A proinflammatory intestinal environment coincided with expansion, increased circulation, and migration of TNF-producing CD4+ T cells to the tumor bed. Thus, TREM2 remotely controls anti-PD-1 immune checkpoint blockade through modulation of the intestinal immune environment and microbiota, with R. gnavus emerging as a potential probiotic agent for increasing responsiveness to anti-PD-1.

Deficiency of IL-22-binding protein enhances the ability of the gut microbiota to protect against enteric pathogens.

Interleukin 22 (IL-22) promotes intestinal barrier integrity, stimulating epithelial cells to enact defense mechanisms against enteric infections, including the production of antimicrobial peptides. IL-22 binding protein (IL-22BP) is a soluble decoy encoded by the Il22ra2 gene that decreases IL-22 bioavailability, attenuating IL-22 signaling. The impact of IL-22BP on gut microbiota composition and functioning is poorly understood. We found that Il22ra2-/- mice are better protected against Clostridioides difficile and Citrobacter rodentium infections. This protection relied on IL-22-induced antimicrobial mechanisms before the infection occurred, rather than during the infection itself. Indeed, the gut microbiota of Il22ra2-/- mice mitigated infection of wild-type (WT) mice when transferred via cohousing or by cecal microbiota transplantation. Indicator species analysis of WT and Il22ra2-/- mice with and without cohousing disclosed that IL22BP deficiency yields a gut bacterial composition distinct from that of WT mice. Manipulation of dietary fiber content, measurements of intestinal short-chain fatty acids and oral treatment with acetate disclosed that resistance to C. difficile infection is related to increased production of acetate by Il22ra2-/--associated microbiota. Together, these findings suggest that IL-22BP represents a potential therapeutic target for those at risk for or with already manifest infection with this and perhaps other enteropathogens.

Prevotella copri and microbiota members mediate the beneficial effects of a therapeutic food for malnutrition.

Microbiota-directed complementary food (MDCF) formulations have been designed to repair the gut communities of malnourished children. A randomized controlled trial demonstrated that one formulation, MDCF-2, improved weight gain in malnourished Bangladeshi children compared to a more calorically dense standard nutritional intervention. Metagenome-assembled genomes from study participants revealed a correlation between ponderal growth and expression of MDCF-2 glycan utilization pathways by Prevotella copri strains. To test this correlation, here we use gnotobiotic mice colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains, with or without P. copri isolates closely matching the metagenome-assembled genomes. Combining gut metagenomics and metatranscriptomics with host single-nucleus RNA sequencing and gut metabolomic analyses, we identify a key role of P. copri in metabolizing MDCF-2 glycans and uncover its interactions with other microbes including Bifidobacterium infantis. P. copri-containing consortia mediated weight gain and modulated energy metabolism within intestinal epithelial cells. Our results reveal structure-function relationships between MDCF-2 and members of the gut microbiota of malnourished children with potential implications for future therapies.

Myoelectric, Myo-Oxygenation, and Myotonometry Changes during Robot-Assisted Bilateral Arm Exercises with Varying Resistances.

Robot-assisted bilateral arm training has demonstrated its effectiveness in improving motor function in individuals post-stroke, showing significant enhancements with increased repetitions. However, prolonged training sessions may lead to both mental and muscle fatigue. We conducted two types of robot-assisted bimanual wrist exercises on 16 healthy adults, separated by one week: long-duration, low-resistance workouts and short-duration, high-resistance exercises. Various measures, including surface electromyograms, near-infrared spectroscopy, heart rate, and the Borg Rating of Perceived Exertion scale, were employed to assess fatigue levels and the impacts of exercise intensity. High-resistance exercise resulted in a more pronounced decline in electromyogram median frequency and recruited a greater amount of hemoglobin, indicating increased muscle fatigue and a higher metabolic demand to cope with the intensified workload. Additionally, high-resistance exercise led to increased sympathetic activation and a greater sense of exertion. Conversely, engaging in low-resistance exercises proved beneficial for reducing post-exercise muscle stiffness and enhancing muscle elasticity. Choosing a low-resistance setting for robot-assisted wrist movements offers advantages by alleviating mental and physiological loads. The reduced training intensity can be further optimized by enabling extended exercise periods while maintaining an approximate dosage compared to high-resistance exercises.

Bioactive glycans in a microbiome-directed food for children with malnutrition.

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1-4. Here we analyse biospecimens from a randomized, controlled trial of a microbiome-directed complementary food (MDCF-2) that produced superior rates of weight gain compared with a calorically more dense conventional ready-to-use supplementary food in 12-18-month-old Bangladeshi children with moderate acute malnutrition4. We reconstructed 1,000 bacterial genomes (metagenome-assembled genomes (MAGs)) from the faecal microbiomes of trial participants, identified 75 MAGs of which the abundances were positively associated with ponderal growth (change in weight-for-length Z score (WLZ)), characterized changes in MAG gene expression as a function of treatment type and WLZ response, and quantified carbohydrate structures in MDCF-2 and faeces. The results reveal that two Prevotella copri MAGs that are positively associated with WLZ are the principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilizing the component glycans of MDCF-2. The predicted specificities of carbohydrate-active enzymes expressed by their polysaccharide-utilization loci are correlated with (1) the in vitro growth of Bangladeshi P. copri strains, possessing varying degrees of polysaccharide-utilization loci and genomic conservation with these MAGs, in defined medium containing different purified glycans representative of those in MDCF-2, and (2) the levels of faecal carbohydrate structures in the trial participants. These associations suggest that identifying bioactive glycan structures in MDCFs metabolized by growth-associated bacterial taxa will help to guide recommendations about their use in children with acute malnutrition and enable the development of additional formulations.

Prevotella copri-related effects of a therapeutic food for malnutrition.

Preclinical and clinical studies are providing evidence that the healthy growth of infants and children reflects, in part, healthy development of their gut microbiomes1-5. This process of microbial community assembly and functional maturation is perturbed in children with acute malnutrition. Gnotobiotic animals, colonized with microbial communities from children with severe and moderate acute malnutrition, have been used to develop microbiome-directed complementary food (MDCF) formulations for repairing the microbiomes of these children during the weaning period5. Bangladeshi children with moderate acute malnutrition (MAM) participating in a previously reported 3-month-long randomized controlled clinical study of one such formulation, MDCF-2, exhibited significantly improved weight gain compared to a commonly used nutritional intervention despite the lower caloric density of the MDCF6. Characterizing the 'metagenome assembled genomes' (MAGs) of bacterial strains present in the microbiomes of study participants revealed a significant correlation between accelerated ponderal growth and the expression by two Prevotella copri MAGs of metabolic pathways involved in processing of MDCF-2 glycans1. To provide a direct test of these relationships, we have now performed 'reverse translation' experiments using a gnotobiotic mouse model of mother-to-offspring microbiome transmission. Mice were colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains cultured from Bangladeshi infants/children in the study population, with or without P. copri isolates resembling the MAGs. By combining analyses of microbial community assembly, gene expression and processing of glycan constituents of MDCF-2 with single nucleus RNA-Seq and mass spectrometric analyses of the intestine, we establish a principal role for P. copri in mediating metabolism of MDCF-2 glycans, characterize its interactions with other consortium members including Bifidobacterium longum subsp. infantis, and demonstrate the effects of P. copri-containing consortia in mediating weight gain and modulating the activities of metabolic pathways involved in lipid, amino acid, carbohydrate plus other facets of energy metabolism within epithelial cells positioned at different locations in intestinal crypts and villi. Together, the results provide insights into structure/function relationships between MDCF-2 and members of the gut communities of malnourished children; they also have implications for developing future prebiotic, probiotic and/or synbiotic therapeutics for microbiome restoration in children with already manifest malnutrition, or who are at risk for this pervasive health challenge.

Bioactive glycans in a microbiome-directed food for malnourished children.

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1-4. Designing effective microbiome-directed therapeutic foods to repair these perturbations requires knowledge about how food components interact with the microbiome to alter its expressed functions. Here we use biospecimens from a randomized, controlled trial of a microbiome-directed complementary food prototype (MDCF-2) that produced superior rates of weight gain compared to a conventional ready-to-use supplementary food (RUSF) in 12-18-month-old Bangladeshi children with moderate acute malnutrition (MAM)4. We reconstructed 1000 bacterial genomes (metagenome-assembled genomes, MAGs) present in their fecal microbiomes, identified 75 whose abundances were positively associated with weight gain (change in weight-for-length Z score, WLZ), characterized gene expression changes in these MAGs as a function of treatment type and WLZ response, and used mass spectrometry to quantify carbohydrate structures in MDCF-2 and feces. The results reveal treatment-induced changes in expression of carbohydrate metabolic pathways in WLZ-associated MAGs. Comparing participants consuming MDCF-2 versus RUSF, and MDCF-2-treated children in the upper versus lower quartiles of WLZ responses revealed that two Prevotella copri MAGs positively associated with WLZ were principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilization of its component glycans. Moreover, the predicted specificities of carbohydrate active enzymes expressed by polysaccharide utilization loci (PULs) in these two MAGs correlate with the (i) in vitro growth of Bangladeshi P. copri strains, possessing differing degrees of PUL and overall genomic content similarity to these MAGs, cultured in defined medium containing different purified glycans representative of those in MDCF-2, and (ii) levels of carbohydrate structures identified in feces from clinical trial participants. In the accompanying paper5, we use a gnotobiotic mouse model colonized with age- and WLZ-associated bacterial taxa cultured from this study population, and fed diets resembling those consumed by study participants, to directly test the relationship between P. copri, MDCF-2 glycan metabolism, host ponderal growth responses, and intestinal gene expression and metabolism. The ability to identify bioactive glycan structures in MDCFs that are metabolized by growth-associated bacterial taxa will help guide recommendations about use of this MDCF for children with acute malnutrition representing different geographic locales and ages, as well as enable development of bioequivalent, or more efficacious, formulations composed of culturally acceptable and affordable ingredients.

Trends and treatments of pelvic and acetabular fractures in Taiwan: facing an aging society.

Pelvic-acetabular fractures lead to high mortality in elders and their association between different groups is not known. Our results indicate that older age with pelvic-acetabular fracture was significantly associated with mortality. This finding may help planning and allocating healthcare resources, risk stratification, and optimizing the treatment of pelvic fractures. PURPOSE: Pelvic or acetabular fractures are among main outcomes of low-energy trauma such as falls, especially in older adults. They represent approximately 3-8% of all fractures and are associated with a high mortality rate ranging from 4 to 28%. This study is aimed at comparing the incidence and trends of hip fractures and pelvic-acetabular fractures in the Taiwanese general population, gender differences in adults aged over 65 years, and mortality risk between pelvic or acetabular fractures and hip fractures and surgery trends in patients with these fractures. METHODS: A retrospective study was conducted extracting data from the National Health Insurance Research Database of patients diagnosed with hip fracture and pelvic acetabular fracture between 2000 and 2018. RESULTS: Older age with pelvic-acetabular fracture was significantly associated with increased mortality. No significant differences were found in comorbidities between the two fracture groups. Results provide clear epidemiological evidence for trends in pelvic-acetabular fractures in Taiwan and demonstrate the need for better strategies to manage these fractures and comorbidities, particularly in older adults. CONCLUSION: Findings of this study may aid in planning and allocating healthcare resources, risk stratification, and optimizing the treatment of pelvic fractures among older adults in Taiwan.

Clinical Outcomes of Single Versus Double Plating in Distal-Third Humeral Fractures Caused by Arm Wrestling: A Retrospective Analysis.

Background and Objectives: Arm wrestling is a simple and popular activity among young people that causes distal-third humeral fractures. However, injury to the young population may cause economic loss; therefore, they need to return to work as soon as possible. Accordingly, we aimed to compare radiological and functional outcomes of distal-third humeral fractures caused by arm wrestling treated with double and single plating. Materials and Methods: Thirty-four patients with distal-third humeral fractures caused by arm wrestling were treated between January 2015 and January 2021. They were separated into double- and single-plating groups and treated using a triceps-sparing approach. Regular follow-up was performed to evaluate elbow functionality, range of motion, bone union, and complications; the American Shoulder and Elbow Surgeons score was used for functional assessment. Results: Patients treated with single plating exhibited union rate, union time, and elbow range of motion similar to those of patients treated with double plating; however, they exhibited better pain and functional outcomes (American Shoulder and Elbow Surgeons score) at 2 weeks, 1 month, and 3 months postoperatively (84.50 ± 5.01 vs. 61.70 ± 12.53 at 2 weeks, 96.20 ± 2.63 vs. 84.25 ± 14.56 at 1 month, and 100.00 vs. 94.76 ± 9.71 at 3 months, p < 0.05). The two groups exhibited no significant differences after 1 year (100.00 vs. 98.54 ± 3.99, p < 0.13). The overall complication rate was significantly higher in patients treated with double plating than in those treated with single plating (18.75% vs. 5.56%). Radial nerve palsy was observed in patients in both groups. Conclusions: In patients with distal-third humeral fractures caused by arm wrestling, single plating provides a union rate and elbow range of motion similar to those of double plating, with significantly fewer complications and lower surgical time and blood loss with improved early functional outcomes.

Perioperative Radiographic Predictors of Non-Union in Infra-Isthmal Femoral Shaft Fractures after Antegrade Intramedullary Nailing: A Case-Control Study.

Antegrade intramedullary (IM) nailing is the gold standard treatment for femoral shaft fractures; however, the non-union rate of infra-isthmal femoral shaft fractures is still high after antegrade IM nailing. This retrospective case−control study aimed to determine the association between perioperative radiographic factors and the non-union of infra-isthmal femoral shaft fractures after antegrade IM nailing. Univariate and multivariate analyses were used to evaluate the radiographic risk factors of non-union. Ninety-three patients were included, with thirty-one non-unions and sixty-two matched controls between 2007 and 2017. All were regularly followed up for 2 years. Receiver operating characteristic analysis revealed that a ratio of the unfixed distal segment > 32.5% was strongly predictive of postoperative non-union. The risk factors for non-union were AO/OTA type B and C (odds ratio [OR]: 2.20), a smaller ratio of the distal fragment (OR: 4.05), a greater ratio of the unfixed distal segment (OR: 7.16), a higher ratio of IM canal diameter to nail size at the level of fracture (OR: 6.23), and fewer distal locking screws (OR: 2.31). The radiographic risk factors for non-union after antegrade IM nailing for infra-isthmal femoral shaft fractures were unstable fractures, shorter distal fragments, longer unfixed distal fragments, wider IM canal, and fewer distal locking screws. Surgeons must strive to avoid non-union with longer and larger nails and apply more distal locking screws, especially for unstable, wider IM canal, and shorter distal fragment fractures.

Arthroscopy-Assisted Reduction and Internal Fixation versus Open Reduction and Internal Fixation for Glenoid Fracture with Scapular Involvement: A Retrospective Cohort Study.

BACKGROUND: We investigated the superiority of arthroscopy-assisted reduction and internal fixation (ARIF) to open reduction and internal fixation (ORIF) for treating glenoid fracture with scapular involvement. METHODS: We retrospectively enrolled patients with glenoid fracture who underwent ARIF or ORIF from 2010-2020. Radiographic outcomes were assessed, and clinical outcomes (active range of motion [ROM], visual analog scale [VAS], Constant, and Disabilities of the Arm, Shoulder and Hand [DASH]) were evaluated 12 months postoperatively. RESULTS: Forty-four patients with Ideberg type II-VI glenoid fractures (ARIF: 20; ORIF: 24; follow-up 12-22 months) were included. Union was achieved in all patients. Active ROM values were comparable between the approaches. Constant and DASH scores were non-significantly better with ARIF (90.9 ± 9.2 vs. 86.6 ± 18.1 [p = 0.341] and 6.8 ± 9.4 vs. 9.3 ± 21.3 [p = 0.626], respectively). However, VAS scores were significantly lower with ARIF (1.5 ± 0.6 vs. 2.7 ± 1.4, p = 0.001). Associated intra-articular lesions (articular depressions [80%], superior labral anterior-posterior tear [20%], labral tears [30%]) were found in most ARIF cases and were repaired during ARIF. CONCLUSIONS: For glenoid fracture with scapular involvement, ARIF allows accurate diagnosis of fracture pattern and the management of associated intra-articular lesions, with better pain control outcomes than ORIF. Thus, arthroscopy-assistant surgery should be considered in patient with glenoid fracture.

Mechanism of Tongbi Jiangu Prescription in Treatment of Knee Osteoarthritis Based on Network Pharmacology and Molecular Docking / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Tongbi Jiangu prescription （TBJG） in the treatment of knee osteoarthritis （KOA） based on network pharmacology and molecular docking，and further verify it by cell experiments. MethodThe active components and the corresponding targets of TBJG were screened out according to the traditional Chinese medicine systems pharmacology database and analysis platform（TCMSP）. The targets of KOA were obtained from GeneCards，online mendelian inheritance in man（OMIM）， and DrugBank. The common targets of active components of TBJG and KOA were the targets of TBJG against KOA. The active component-target network and protein-protein interaction （PPI） network were constructed by Cytoscape 3.7.2. STRING was used for PPI network analysis. DAVID was used for gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses. Key targets and core active components were selected for molecular docking by AutoDock. The results of network pharmacology were verified by cell experiments and the pharmacodynamic responses were observed. ResultThe prediction of network pharmacology showed that there were 111 active components of TBJG in the treatment of KOA. The core active components were quercetin，kaempferol， and β-sitosterol，and the key targets were interleukin-1β（IL-1β）， matrix metalloproteinase-3 （MMP-3），and tumor necrosis factor-α （TNF-α）. Biological processes （BP） in GO analysis mainly involved inflammatory response，response to lipopolysaccharide，apoptosis signaling pathway，and regulation of DNA activity in binding transcription factor. Cellular components （CC） included plasma membrane protein complex，RNA polymerase Ⅱ transcription factor complex，membrane raft，and serine/threonine protein kinase complex. Molecular functions （MF） were mainly enriched in cytokine receptor binding，nuclear receptor activity，protein domain specific binding，serine hydrolase activity，chemokine receptor binding，and activity of nitric oxide synthase regulator. As revealed by the KEGG analysis， the relevant signaling pathways were nuclear factor（NF）-κB， Janus kinase（JAK）/signal transducer and activator of transcription（STAT）， and Wnt signaling pathways. Molecular docking results showed that the core active components had good binding activities with key targets. The experimental results showed that TBJG could down-regulate IL-1β， MMP-3，TNF-α， and NF-κB p65 expression levels （P<0.05），and up-regulated NF-κB inhibitor（IκB）-α（P<0.05）. ConclusionThe mechanism of TBJG in the treatment of KOA lies in the application of active components such as quercetin，kaempferol， and β-sitosterol with IL-1β，MMP-3， and TNF-α as key targets through the NF-κB，JAK/STAT， and Wnt signaling pathways.

Isolated Middle-Third Clavicle Fracture Causing Horner's Syndrome: A Case Report and Literature Review.

The pathophysiology of Horner's syndrome arises due to compression or destruction of the oculosympathetic nerve pathway. Traumatic Horner's syndrome may indicate lethal neurovascular injury, such as brain stem lesion, cervical spine injury, or carotid artery dissection. The middle-third is the most common type of clavicle fracture. However, the association of the isolated middle-third clavicle fracture and Horner's syndrome is rare. We report the case of a 47 year-old woman who presented to our emergency department with acute trauma. Severe tenderness and limited mobility were observed in her left shoulder. On radiographic examination, a middle-third clavicle fracture was diagnosed. Ptosis and myosis were also noticed on further examination, and she was subsequently diagnosed with Horner's syndrome. A survey of the brain, cervical spine, carotid artery, and lung revealed no pathological findings. Surgery for the clavicle fracture was performed 2 days after the accident. The patient recovered from Horner's syndrome gradually over the 2 months following the surgery, and the syndrome completely resolved by the third month. To the best of our knowledge, this is the first report of traumatic Horner's syndrome caused by an isolated middle-third clavicle fracture. The improved outcome may be attributed to the surgical intervention for middle-third clavicle fracture, which may help release ganglion or neuronal compression.

Gut microbiome contributions to altered metabolism in a pig model of undernutrition.

The concept that gut microbiome-expressed functions regulate ponderal growth has important implications for infant and child health, as well as animal health. Using an intergenerational pig model of diet restriction (DR) that produces reduced weight gain, we developed a feature-selection algorithm to identify representative characteristics distinguishing DR fecal microbiomes from those of full-fed (FF) pigs as both groups consumed a common sequence of diets during their growth cycle. Gnotobiotic mice were then colonized with DR and FF microbiomes and subjected to controlled feeding with a pig diet. DR microbiomes have reduced representation of genes that degrade dominant components of late growth-phase diets, exhibit reduced production of butyrate, a key host-accessible energy source, and are causally linked to reduced hepatic fatty acid metabolism (ß-oxidation) and the selection of alternative energy substrates. The approach described could aid in the development of guidelines for microbiome stewardship in diverse species, including farm animals, in order to support their healthy growth.

Anthropometric Factors on Safe Distances between Popliteal Vessels to the Femur for Cerclage Wiring of the Distal Femoral Fracture: A Magnetic Resonance Imaging Study.

Background and Objectives: The proximity of the popliteal vessels in the distal femur may increase the risk of iatrogenic vascular injury during cerclage wiring. In this study, the closest location and distance of the popliteal vessels to the femur was examined using magnetic resonance imaging (MRI). The associations between anthropometric factors and the distance that would guide the placement of wires safely during surgery were also identified. Materials and Methods: We reviewed adult knee magnetic resonance images and recorded: (1) the relation and the shortest horizontal distance (d-H) from the femoral cortex to the popliteal vessels in axial images and (2) the vertical distance (d-V) from the adductor tubercle to the axial level of the d-H values in coronal images. The effects of anthropometric factors (sex, age, body height, body weight, body mass index, thigh circumference, femoral length and femoral width) on these distances were analysed. Results: Analysis of 206 knee magnetic resonance images revealed that the closet locations of popliteal vessels were at the posteromedial aspect of the femur. The d-H and d-V were 7.38 ± 3.22 mm and 57.01 ± 11.14 mm, respectively, and were both shorter in women than in men (p < 0.001). Multivariate analysis identified thigh circumference and femoral length as the most influential factors for the d-H and d-V, respectively (p < 0.001). Linear regression demonstrated a strong positive linear correlation between the thigh circumference and the d-H and between the femoral length and the d-V (Pearson's r = 0.891 and 0.806, respectively (p < 0.001)). Conclusions: The closet location and distance of the popliteal vessels to the femur provide useful information for wire placement during distal femoral fracture surgery while minimising the risk of vascular injury. Given that patients with a smaller thigh circumference and a shorter femoral length are more likely to have a smaller d-H and a shorter d-V, respectively, cautious measures should be taken in such cases.

Preliminary clinical and radiographic outcomes of proximal humeral fractures: comparison of ALPS and PHILOS plating in Asian patients in Taiwan.

BACKGROUND: Up to 20% of proximal humeral fractures need to be treated operatively. However, numerus complications were reported by using fixed angled locking plates. The ALPS Proximal Humerus Plating System is a new design implant with novel design features. The aim of this study was to compare the preliminary clinical outcomes and complications of proximal humeral fractures treated with either ALPS or the proximal humeral internal locking system (PHILOS) in Asian patients in Taiwan. METHODS: Between January 2016 and December 2018, 66 patients with displaced proximal humeral fractures were analyzed retrospectively, of whom 31 underwent ALPS implant treatment and 35 underwent PHILOS implant treatment. Intraoperative blood loss and operation time, postoperative Constant-Murley Shoulder Outcome (Constant-Murley) score, and complications variables were recorded for the comparison. All cases were regularly followed up for at least 1 year. RESULTS: The mean follow-up period was 400.8 days (range, 367-446 days). Union was achieved in 98.5% of patients (65/66). The ALPS group yielded similar radiologic and clinical outcomes to the PHILOS plating group for treating displaced proximal humeral fractures, including operation time, intraoperative blood loss, the Constant-Murley score, and varus malunion (P > 0.05, respectively). However, the incidence of total postoperative complications in the ALPS group was significantly lower than in the PHILOS group (P < 0.05). There was a trend of a lower complication rate of screws/pegs protrusion, avascular necrosis, subacromial impingement, postoperative infection, and reoperation in the ALPS group, although it was not statistically significant (P > 0.05, respectively). CONCLUSION: The ALPS group yielded similar radiologic and clinical outcomes to the PHILOS plating group for displaced proximal humeral fractures, but the ALPS group had a significantly lower total rate of complications. Therefore, ALPS may be a better option for treating proximal humeral fractures. Further larger clinical studies are needed to confirm the findings presented here. TRIAL REGISTRATION: Retrospective study.

Inline Inspection with an Industrial Robot (IIIR) for Mass-Customization Production Line.

Robots are essential for the rapid development of Industry 4.0. In order to truly achieve autonomous robot control in customizable production lines, robots need to be accurate enough and capable of recognizing the geometry and orientation of an arbitrarily shaped object. This paper presents a method of inline inspection with an industrial robot (IIIR) for mass-customization production lines. A 3D scanner was used to capture the geometry and orientation of the object to be inspected. As the object entered the working range of the robot, the end effector moved along with the object and the camera installed at the end effector performed the requested optical inspections. The detailed information about the developed methodology was introduced in this paper. The experiments showed there was a relative movement between the moving object and the following camera and the speed was around 0.34 mm per second (worst case was around 0.94 mm per second). For a camera of 60 frames per second, the relative moving speed between the object and the camera was around 6 micron (around 16 micron for the worst case), which was stable enough for most industrial production inspections.

A sparse covarying unit that describes healthy and impaired human gut microbiota development.

Characterizing the organization of the human gut microbiota is a formidable challenge given the number of possible interactions between its components. Using a statistical approach initially applied to financial markets, we measured temporally conserved covariance among bacterial taxa in the microbiota of healthy members of a Bangladeshi birth cohort sampled from 1 to 60 months of age. The results revealed an "ecogroup" of 15 covarying bacterial taxa that provide a concise description of microbiota development in healthy children from this and other low-income countries, and a means for monitoring community repair in undernourished children treated with therapeutic foods. Features of ecogroup population dynamics were recapitulated in gnotobiotic piglets as they transitioned from exclusive milk feeding to a fully weaned state consuming a representative Bangladeshi diet.

Effects of microbiota-directed foods in gnotobiotic animals and undernourished children.

To examine the contributions of impaired gut microbial community development to childhood undernutrition, we combined metabolomic and proteomic analyses of plasma samples with metagenomic analyses of fecal samples to characterize the biological state of Bangladeshi children with severe acute malnutrition (SAM) as they transitioned, after standard treatment, to moderate acute malnutrition (MAM) with persistent microbiota immaturity. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes targeting weaning-phase bacterial taxa underrepresented in SAM and MAM microbiota were characterized in gnotobiotic mice and gnotobiotic piglets colonized with age- and growth-discriminatory bacteria. A randomized, double-blind controlled feeding study identified a lead MDCF that changes the abundances of targeted bacteria and increases plasma biomarkers and mediators of growth, bone formation, neurodevelopment, and immune function in children with MAM.

A non-canonical autophagy-dependent role of the ATG16L1T300A variant in urothelial vesicular trafficking and uropathogenic Escherichia coli persistence.

50% of Caucasians carry a Thr300Ala variant (T300A) in the protein encoded by the macroautophagy/autophagy gene ATG16L1. Here, we show that the T300A variant confers protection against urinary tract infections (UTIs), the most common infectious disease in women. Using knockin mice carrying the human T300A variant, we show that the variant limits the UTI-causing bacteria, uropathogenic Escherichia coli (UPEC), from establishing persistent intracellular reservoirs, which can seed UTI recurrence. This phenotype is recapitulated in mice lacking Atg16l1 or Atg7 exclusively in the urothelium. We further show that mice with the T300A variant exhibit urothelial cellular abnormalities, including vesicular congestion and aberrant accumulation of UPK (uroplakin) proteins. Importantly, presence of the T300A variant in humans is associated with similar urothelial architectural abnormalities, indicating an evolutionarily conserved impact. Mechanistically, we show that the reduced bacterial persistence is independent of basal autophagic flux or proinflammatory cytokine responses and does not involve Atg14 or Epg5. However, the T300A variant is associated with increased expression of the small GTPase Rab33b; RAB33B interacts with ATG16L1, as well as other secretory RABs, RAB27B and RAB11A, important for UPEC exocytosis from the urothelium. Finally, inhibition of secretory RABs in bladder epithelial cells increases intracellular UPEC load. Together, our results reveal that UPEC selectively utilize genes important for autophagosome formation to persist in the urothelium, and that the presence of the T300A variant in ATG16L1 is associated with changes in urothelial vesicle trafficking, which disrupts the ability of UPEC to persist, thereby limiting the risk of recurrent UTIs. Abbreviations: 3-PEHPC: 3-pyridinyl ethylidene hydroxyl phosphonocarboxylate; ATG: autophagy; ATG16L1: autophagy related 16 like 1; BECs: bladder epithelial cells; dpi: days post infection; hpi: hours post infection; IF: immunofluorescence; IL1B: interleukin 1 beta; IL6: interleukin 6; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MVB: multivesicular bodies; T300A: Thr300Ala; TNF: tumor necrosis factor; QIR(s): quiescent intracellular reservoir(s); siRNA: short interfering RNA; UPEC: uropathogenic Escherichia coli; UTI(s): urinary tract infection(s); TEM: transmission electron microscopy; WT: wild type.