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The nanoparticles of bentonite can be easily synthesized by hydrothermal treatment with microwave-assisted method. The products were characterized by XRD, FTIR, BET, SEM, EDS, and DLS. Results have revealed that the nano-bentonite was in nanometer scale with particles size of 200–300 nm. The SEM analysis of the nano-bentonite dispersion showed that a decrease in agglomeration and surface roughness. The nano-bentonite possessed high surface area (152.4 m ^2 .g ^−1 ) and pore volume (0.25 cm ^3 .g ^−1 ). Additionally, nanocomposite hydrogels (NB/PAA) were synthesized through the free-radical polymerization of acrylic acid (PAA) in the presence of the as-synthesized nano-bentonite (NB). The presence of NB in hydrogel matrix may improve the tensile strength of hydrogel. The tensile strength of the hydrogel increases from 0.294 to 1.609 MPa when NB content was 1.0% (NB10/PAA). Under the optimum conditions, the nanocomposite hydrogels (NB10/PAA) exhibited high water absorption capacity of 420.0 ${g}_{water}.{g}_{hydrogel}^{-1}.$ These findings contribute to the sustainable development and green chemistry.

Copper (I) chloride (CuCl) modified graphene oxide with different copper (Cu) content were prepared by ‘ion implantation’ method using CuCl as Cu source. The samples were characterized by x-ray Powder Diffraction-XRD, FTIR, BET, SEM, TEM, EDS and x-ray photoelectron spectroscopy-XPS. From TEM images and EDS elemental mapping, it showed the CuCl particles of 30–50 nm with high dispersion on graphene oxide surface. From XPS result, it revealed the presence of both Cu ^+ and Cu ^2+ ions but Cu ^+ ion amount was predominant. CO adsorption on CuCl modified graphene oxide with different Cu content was tested. Among tested CuCl modified GO samples, 2CuCl/GO sample exhibited the highest CO gas adsorption capacity of 2.9 mmol g ^−1 at 20 °C which was 7.5 times higher than that of pristine GO (0.38 mmol g ^−1 ). High CO adsorption performance on CuCl modified GO can be explained by the formation of π –complexation between CO molecules and Cu(I) ions. From CO adsorption on CuCl modified GO, it showed that the experimental data fit well with Langmuir- Freundlich model.

Microbial exopolysaccharides (EPSs) are receiving growing interest today, owing to their diversity in chemical structure and source, multiple functions, and immense potential applications in many food and non-food industries. Their health-promoting benefits for humans deserve particular attention because of their various biological activities and physiological functions. The aim of this paper is to provide a comprehensive review of microbial EPSs, covering (1) their chemical and biochemical diversity, including composition, biosynthesis, and bacterial sources belonging mainly to lactic acid bacteria (LAB) or probiotics; (2) their technological and analytical aspects, especially their production mode and characterization; (3) their biological and physiological aspects based on their activities and functions; and (4) their current and future uses in medical and pharmaceutical fields, particularly for their prebiotic, anticancer, and immunobiotic properties, as well as their applications in other industrial and agricultural sectors.

Bacterial exopolysaccharides (EPS) are biopolymers of carbohydrates, often released from cells into the extracellular environment. Due to their distinctive physicochemical properties, biocompatibility, biodegradability, and non-toxicity, EPS finds applications in various industrial sectors. However, the need for alternative EPS has grown over the past few decades as lactic acid bacteria's (LAB) low-yield EPS is unable to meet the demand. In this case, rhizosphere bacteria with the diverse communities in soil leading to variations in composition and structure, are recognized as a potential source of EPS applicable in various industries. In addition, media components and cultivation conditions have an impact on EPS production, which ultimately affects the quantity, structure, and biological functions of the EPS. Therefore, scientists are currently working on manipulating bacterial EPS by developing cultures and applying abiotic and biotic stresses, so that better production of exopolysaccharides can be attained. This review highlights the composition, biosynthesis, and effects of environmental factors on EPS production along with the potential applications in different fields of industry. Ultimately, an overview of potential future paths and tactics for improving EPS implementation and commercialization is pointed out., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To describe late transplant-associated thrombotic microangiopathy (TA-TMA) as chronic endothelial complication in bone marrow (BM) after allogeneic hematopoietic stem cell transplantation (HSCT)., Methods: BM specimens along with conventional diagnostic parameters were assessed in 14 single-institutional patients with late TA-TMA (more than 100 days after HCST), including 11 late with history of early TA-TMA, 10 with early TA-TMA (within 100 days), and 12 non TA-TMA patients. Three non-HSCT patients served as control. The time points of BM biopsy were +1086, +798, +396, and +363 days after HSCT, respectively., Results: Late TA-TMA patients showed an increase of CD34+ and von Willebrand Factor (VWF)+ microvascular endothelial cells with atypical VWF+ conglomerates forming thickened VWF+ plaque sinus in the BM compared to patients without late TA-TMA and non-HSCT. Severe chronic (p = .002), steroid-refractory GVHD (p = .007) and reactivation of HHV6 (p = .002), EBV (p = .003), and adenovirus (p = .005) were pronounced in late TA-TMA. Overall and relapse-free survival were shorter in late TA-TMA than in patients without late TA-TMA (5-year OS and RFS: 78.6% vs. 90.2%, 71.4% vs. 86.4%, respectively)., Conclusion: Chronic allo-immune microangiopathy in BM associated with chronic, steroid-refractory GVHD and/or viral infections are key findings of late, high-risk TA-TMA, which deserves clinical attention., (© 2024 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

The shift towards sustainable feedstocks for platform chemicals requires new routes to access functional molecules that contain heteroatoms, but there are limited bio-derived feedstocks that lead to heteroatoms in platform chemicals. Combining renewable molecules of different origins could be a solution to optimize the use of atoms from renewable sources. However, the lack of retrosynthetic tools makes it challenging to examine the extensive reaction networks of various platform molecules focusing on multiple bio-based feedstocks. In this study, a protocol was developed to identify potential transformation pathways that allow for the use of feedstocks from different origins. By analyzing existing knowledge on chemical reactions in large databases, several promising synthetic routes were shortlisted, with the reaction of D-glucosamine and pyruvic acid being the most interesting to make pyrrole-2-carboxylic acid (PCA). The optimized synthetic conditions resulted in 50 % yield of PCA, with insights gained from temperature variant NMR studies. The use of substrates obtained from two different bio-feedstock bases, namely cellulose and chitin, allowed for the establishment of a PCA-based chemical space., (© 2023 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Background: Tackling the spread of COVID-19 remains a crucial part of ending the pandemic. Its highly contagious nature and constant evolution coupled with a relative lack of immunity make the virus difficult to control. For this, various strategies have been proposed and adopted including limiting contact, social isolation, vaccination, contact tracing, etc. However, given the heterogeneity in the enforcement of these strategies and constant fluctuations in the strictness levels of these strategies, it becomes challenging to assess the true impact of these strategies in controlling the spread of COVID-19., Methods: In the present study, we evaluated various transmission control measures that were imposed in 10 global urban cities and provinces in 2021- Bangkok, Gauteng, Ho Chi Minh City, Jakarta, London, Manila City, New Delhi, New York City, Singapore, and Tokyo., Findings: Based on our analysis, we herein propose the population-level Swiss cheese model for the failures and pitfalls in various strategies that each of these cities and provinces had. Furthermore, whilst all the evaluated cities and provinces took a different personalized approach to managing the pandemic, what remained common was dynamic enforcement and monitoring of breaches of each barrier of protection. The measures taken to reinforce the barriers were adjusted continuously based on the evolving epidemiological situation., Interpretation: How an individual city or province handled the pandemic profoundly affected and determined how the entire country handled the pandemic since the chain of transmission needs to be broken at the very grassroot level to achieve nationwide control., Funding: The present study did not receive any external funding., Competing Interests: The authors declare no conflicts of interests with regards to the present study. Authors did not receive any external funding for the study., (© 2022 The Author(s).)

A highly stereoselective asymmetric total synthesis of (-)-jimenezin ( 1 ), a potent anticancer acetogenin, was efficiently completed with the key feature being a sequential intramolecular amide enolate alkylation (IAEA). Our investigation to probe the origin of the complete stereoselectivity in the second IAEA step to form the conformationally flexible tetrahydrofuran with perfect stereocontrol identified the presence of the oxygen atom in the adjacent tetrahydropyran ring to be crucial.

Improvement of antioxidant and anti-inflammatory functions is believed to be an effective strategy for protection against various diseases such as cancer, aging, and neurodegenerative disease. This study focused on investigating antioxidant and anti-inflammatory abilities of Zingiber montanum oil (ZMO) extracted by the supercritical CO 2 fluid system in HepG2 cells and lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Ten predominant constituents of ZMO were identified, in which triquinacene, 1,4-bis (methoxy), terpinen-4-ol, triquinacene, 1,4,7-tris (methoxy), α -terpinene, sabinene hydrate, and ( E and Z )-1-(3,4-dimethoxyphenyl)butadiene account for 86.47%. ZMO exhibited anti-inflammatory capacity by inhibiting the formation of pro-inflammatory markers such as nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, interleukin (IL)-1 β , IL-6, and monocyte chemoattractant protein-1 in LPS-treated macrophages. The LPS-induced stimulation of nuclear factor-kappa B, signal transducer and activator of transcription 3 (Stat3) and mitogen-activated protein kinase (MAPK) pathways as evident from increased phosphorylation of IKK α / β , I κ B α , p65, Stat3, ERK, JNK, and p38 MAPK was also suppressed by ZMO pretreatment. Further, ZMO enhanced the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1), and concurrently, reduced intracellular reactive oxygen species accumulation in LPS-treated RAW 264.7 cells. In addition, ZMO treatment markedly upregulated the expression of Nrf2 as well as its target genes, HO-1 and NAD(P)H:quinone oxidoreductase 1 in HepG2 cells. These data propose that ZMO may be a potent candidate for prevention and/or treatment of inflammatory and oxidative conditions.

BACKGROUND Implantation of the Actifit® polyurethane meniscal scaffold is indicated for knee pain after partial meniscectomy in adults who are skeletally mature. This report is of a case of implantation of an Actifit® polyurethane meniscal scaffold 18 months after subtotal lateral meniscectomy in a 13-year-old male adolescent. CASE REPORT A 13-year-old male presented with right knee pain, localized to the lateral joint, 18 months after undergoing subtotal lateral meniscectomy. Magnetic resonance imaging (MRI) of the knee showed a complete amputation of the lateral meniscal middle segment with subchondral bone damage. Arthroscopic exploration of the knee joint showed a subtotal posterior and middle lateral meniscectomy and a 4 cm² area of International Cartilage Repair Society (ICRS) grade 3 cartilage damage on the posterior aspect of the lateral tibial plateau. The anterolateral portal was enlarged to introduce the Actifit® scaffold. The implant was secured using three all-inside Fast-Fix® sutures and three outside-in vertical sutures, which rapidly reduced the pain symptoms. At five-year follow-up, the patient reported no pain, and he had resumed sporting activities and recovered a full knee range of motion at 0/0/145°. MRI showed a type 2 meniscal implant shape and size, according to the Genovese MRI score. The ICRS MRI score was stable at grade 3b. CONCLUSIONS This case showed that the use of the Actifit® polyurethane meniscal scaffold is an option for the treatment of knee pain after partial or subtotal meniscectomy in skeletally immature patients, resulting in a stable functional outcome at five-year follow-up.

There has been lively debate regarding the rationale behind the use of radial head arthroplasty (RHA) for more than 80 years. Currently, its primary indication is for treatment of non-reconstructible RH fractures. The first RH implant, released in 1941, was a ferrul cap used to prevent heterotopic ossification. Biomechanical studies in the 1980s stimulated a revolution in RHA design by promoting modular implants that replicated the native bony anatomy of the elbow. Subsequent data-driven evolution in design led to the creation of a variety of devices that also accommodated for common ligamentous injuries occurring at the time of RH fracture. Despite significant advances in our understanding of complex elbow instability, improvements in implant design have to make RHA the gold standard for treatment of non-reconstructible RH fractures. The challenge in the coming years will be to perform high-level clinical studies in order to obtain consensus regarding the most appropriate treatment for comminuted RH fractures.

Human rhinoviruses (HRV) are one of the major causes of common cold in humans and are also associated with acute asthma and bronchial illness. Heat-shock protein 90 (Hsp90), a molecular chaperone, is an important host factor for the replication of single-strand RNA viruses. In the current study, we examined the effect of the Hsp90 inhibitor pochonin D, in vitro and in vivo , using a murine model of human rhinovirus type 1B (HRV1B) infection. Our data suggested that Hsp90 inhibition significantly reduced the inflammatory cytokine production and lung damage caused by HRV1B infection. The viral titer was significantly lowered in HRV1B-infected lungs and in Hela cells upon treatment with pochonin D. Infiltration of innate immune cells including granulocytes and monocytes was also reduced in the bronchoalveolar lavage (BAL) by pochonin D treatment after HRV1B infection. Histological analysis of the lung and respiratory tract showed that pochonin D protected the mice from HRV1B infection. Collectively, our results suggest that the Hsp90 inhibitor, pochonin D, could be an attractive antiviral therapeutic for treating HRV infection.

Background: Fractures of the distal radius only rarely give rise to complications in the immediate postoperative period. Combined median and ulnar nerve palsy is a complication that can be missed by the surgeon., Materials and Methods: Three cases diagnosed early after surgery are reported here. The patients were 15, 16, and 30 years of age, respectively. None had preoperative neurological deficits. The youngest patient was injured during sports and the other 2 patients during traffic accidents. All 3 patients had a displaced fracture of the distal radius combined with a fracture of the distal fourth of the ulna or ulnar styloid process and were treated by anterior plate fixation. Operative times were 47, 62, and 120minutes, respectively. Compartment syndrome was ruled out based on low pain intensity and absence of forearm tightness to palpation., Results: The electrophysiological study performed 1 month post-injury in all 3 patients showed severe impairments of both median and ulnar nerve function. Median and ulnar nerve release surgery was performed in the 15-year-old 6 weeks post-injury. No nerve damage or fibrosis was seen during the procedure. All patients recovered fully within 3 months and had normal findings from follow-up electrophysiology testing after 6 months., Discussion: Combined median and ulnar nerve palsy has rarely been reported and is among the rare complications of distal radial fractures that can develop in the event of a high-energy trauma and/or major displacement. Both previously published data and our experience indicate that surgical nerve release is unnecessary. Clinical recovery within 3 months is the rule., Level of Evidence: IV, case-reports., (Copyright © 2018. Published by Elsevier Masson SAS.)

Background: Total elbow arthroplasty is a therapeutic option for severe rheumatoid arthritis. We hypothesized that the semiconstrained characteristics of the Coonrad-Morrey prosthesis do not compromise the survival rate of the implant in a rheumatoid elbow., Methods: Between 1997 and 2012, there were 54 Coonrad-Morrey total elbow prostheses performed for rheumatoid arthritis in 46 patients. Minimum follow-up was 2 years. There were 35 women and 11 men with a mean age of 60 years (29-83 years). According to the Mayo classification for rheumatoid elbow, there were 30 type IIIA, 21 type IIIB, and 3 type IV. The surgical procedure was the same for all patients. Survivorship was assessed with use of the Kaplan-Meier method, with revision surgery as the end point., Results: The survival rate was 97% (95% confidence interval, 83.6-99.6) at 5 years and 85% (95% confidence interval, 68.3-93.7) at 10 years. At an average of 7 years of follow-up (2-16 years), the mean Mayo Elbow Performance Score was 91 points (55-100 points), and the shortened version of the Disabilities of the Arm, Shoulder, and Hand score was 34 points (0-75 points). There was a significant improvement in Mayo Elbow Performance Score and in all range of motion at latest follow-up in comparison to preoperative values (P < .0001). Radiolucencies were observed in 6 cases around the humeral component and in 6 cases around the ulnar component. Bushing wear was observed in 16 cases (29%). There were 14 complications (26%). Revisions were performed in 6 of them (11%)., Conclusion: The Coonrad-Morrey prosthesis provides satisfactory results with follow-up. The rate of complications remains high even if the rate of implant revision stayed low., (Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Purpose: Arthroscopic techniques tend to become the gold standard in rotator cuff repair. However, little data are reported in the literature regarding the improvement of postoperative outcomes and re-tear rate relative to conventional open surgery. The aim of this study was to compare clinical outcomes and cuff integrity after arthroscopic versus open cuff repair., Methods: We prospectively assessed clinical outcomes and cuff integrity after an arthroscopic or open rotator cuff repair with a minimum follow-up of 12 months. Clinical evaluation was based on Constant score, Simple Shoulder Value (SSV) and American Shoulder and Elbow Score (ASES). Rotator cuff healing was explored with ultrasound., Results: 44 patients in arthroscopic group A (mean age 56-year-old) and 43 in open group O (mean age 61-year-old) fulfilled the inclusion criteria. Tendons were repaired with a single row technique associated with biceps tenodesis and subacromial decompression. All objective clinical scores significantly improved postoperatively in both groups. No statistical difference was identified between group A and O regarding, respectively, Constant score (72 vs 75 points; p = 0.3), ASES score (88 vs 91 points; p = 0.3), and SSV (81 vs 85%). The overall rate of re-tear (Sugaya type IV or V) reached 7 and 9%, respectively, in group A and O (p = 0.8)., Conclusion: This study did not prove any difference of arthroscopic over open surgery in case of rotator cuff repair regarding clinical outcome and cuff integrity at 1-year follow-up., Level Ii: Prospective comparative study.

Background: Blount's method is controversial for the treatment of Gartland types IIB and III supracondylar fracture of the humerus (SCFH) in children. The purpose of this study was to evaluate the clinical and radiologic outcomes and the failure and complication rates., Methods: All types IIB and III SCFH treated with Blount's method from 2003-2013 were included in this retrospective single-center study. Clinical assessment was performed according to Flynn criteria. Baumann angle, anteversion angle, anterior humeral line, and humeroulnar angle were measured for radiographic assessment., Results: Among 447 children with types IIB and III SCHF, 339 were treated according to Blount's method. There were 173 boys (51%), and the mean age was 6.3 years (1-14 years); 71% were type III. Mean time to surgery was 5.7 hours. According to Flynn criteria, results were satisfactory in 91% of cases. No compartment syndrome was encountered. There were 16 (4.7%) secondary displacements requiring surgical revision. Five (1.9%) children developed a cubitus varus deformity. At latest follow-up, the mean Baumann angle was 74.7° (95% confidence interval, 74.1-75.3), the mean anteversion angle was 39.9° (95% confidence interval, 39.5-40.3), the anterior humeral line was normal in 87.6% of cases, and the mean humeroulnar angle was 8.7°., Conclusion: Blount's method is appropriate to manage types IIB and III SCFH, provided anatomic and stable reduction is obtained., (Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Lung cancer accounts for the highest death rate among cancers worldwide, with most patients being diagnosed with non-small cell lung cancer (NSCLC), urging more effective therapies. We report that JK273, a pyrrolo[2,3-d]pyrimidine analog, which inhibits α4 integrin signaling, showed a selective cytotoxic effect against HCI-H460 NSCLC cells, with an IC 50 of 0.98 ± 0.15 μM, but showed less sensitivity to fibroblasts with a selectivity index (SI) greater than 30. This effect was attributed to cell cycle arrest at S phase by JK273 treatment, resulting in the apoptosis of NCI-H460 cells, further confirmed by exposing phosphatidylserine and morphological changes. Taken together with the previous study of JK273 inhibiting cell migration, we propose that JK273 could serve as an antitumor compound to specifically target cancer cells but not non-cancerous cells by triggering programmed cell death, in addition to anti-metastatic effects in cancer therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Case: Osteochondritis dissecans (OCD) rarely affects the humeral head. We describe a 14-year-old adolescent who, despite conservative treatment, had persistent pain in the left shoulder as well as limited function. Radiographs and a computed tomography (CT) arthrogram revealed an osteochondral defect of the humeral head. He was managed with an arthroscopic osteochondral autograft transfer from the knee, which provided a satisfactory outcome., Conclusion: Arthroscopic osteochondral autograft transfer is an effective option for the treatment of OCD of the humeral head.

Background: Neurologic lesions are relatively common after total shoulder arthroplasty. These injuries are mostly due to traction. We aimed to identify the arm manipulations and steps during reverse total shoulder arthroplasty (RTSA) that affect nerve stress., Methods: Stress was measured in 10 shoulders of 5 cadavers by use of a tensiometer on each nerve from the brachial plexus, with shoulders in different arm positions and during different surgical steps of RTSA., Results: When we studied shoulder position without prostheses, relative to the neutral position, internal rotation increased stress on the radial and axillary nerves and external rotation increased stress on the musculocutaneous, median, and ulnar nerves. Extension was correlated with increase in stress on all nerves. Abduction was correlated with increase in stress for the radial nerve. We identified 2 high-risk steps during RTSA: humeral exposition, particularly when the shoulder was in a position of more extension, and glenoid exposition. The thickness of polyethylene humeral cups used was associated with increased nerve stress in all but the ulnar nerve., Conclusion: During humeral preparation, the surgeon must be careful to limit shoulder extension. Care must be taken during exposure of the glenoid. Extreme rotation and oversized implants should be avoided to minimize stretch-induced neuropathies., (Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

The first total synthesis and structure revision of (-)-11β-hydroxycurvularin (1b), a macrolide possessing a β-hydroxyketone moiety, were accomplished. The β-hydroxyketone moiety in this natural product was introduced by cleavage of the N-O bond in an isoxazoline ring that was formed diastereoselectively in a 1,5-remote stereocontrolled fashion by employing intramolecular nitrile oxide cycloaddition.

The advantages of employing an interconnected periodic ZnO morphology, i.e. an inverse opal structure, in electrodeposited ZnO/Cu2O devices are presented. The solar cells are fabricated using low cost solution based methods such as spin coating and electrodeposition. The impact of inverse opal geometry, mainly the diameter and thickness, is scrutinized. By employing 3 layers of an inverse opal structure with a 300 nm pore diameter, higher short circuit photocurrents (∼84% improvement) are observed; however the open circuit voltages decrease with increasing interfacial area. Optical simulation using a finite difference time domain method shows that the inverse opal structure modulates light propagation within the devices such that more photons are absorbed close to the ZnO/Cu2O junction. This increases the collection probability resulting in improved short circuit currents.

This study examined the associations between vitamin D status, bone mineral content (BMC), areal bone mineral density (aBMD), and markers of calcium homeostasis in preschool-aged children. Children (n=488; age range: 1.8-6.0 y) were randomly recruited from Montreal. The distal forearm was scanned using a peripheral dual-energy X-ray absorptiometry scanner (Lunar PIXI; GE Healthcare, Fairfield, CT). A subset (n=81) had clinical dual-energy X-ray absorptiometry (cDXA) scans (Hologic 4500A Discovery Series) of lumbar spine (LS) 1-4, whole body, and ultradistal forearm. All were assessed for plasma 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone concentrations (Liaison; Diasorin), ionized calcium (ABL80 FLEX; Radiometer Medical A/S), and dietary vitamin D and calcium intakes by survey. Age (p<0.001) and weight-for-age Z-score (p<0.001) were positively associated with BMC and aBMD in all regression models, whereas male sex contributed positively to forearm BMC and aBMD. Having a 25(OH)D concentration of >75 nmol/L positively associated with forearm and whole body BMC and aBMD (p<0.036). Sun index related to (p<0.029) cDXA forearm and LS 1-4 BMC and whole-body aBMD. Nutrient intakes did not relate to BMC or aBMD. In conclusion, higher vitamin D status is linked to higher BMC and aBMD of forearm and whole body in preschool-aged children., (Copyright © 2015 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Introduction: At the present there are limited tools available to measure muscle function in young children. Ground reaction force plates measure lower-body function and postural control in older children and adults. The purpose of this study was threefold: 1) develop normative data for evaluating global muscle development; 2) determine the reproducibility of ground reaction force plates for assessing muscle function in preschool-age children; and 3) identify predictors of skeletal muscle function., Methods: Children's (n = 81, 1.8 to 6.0 yr; M = 52%) muscle function and postural control was measured for jump (JMP), sit-to-stand (STS), and both undistracted and distracted body sway tests using a ground reaction force plate (Kistler 9200A). Whole body composition used dual-energy x-ray absorptiometry (Hologic 4500A Discovery Series). Plasma 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone concentrations were measured by chemiluminescence (Liaison, Diasorin, Mississauga, ON, Canada) as well as ionized calcium (ABL80 FLEX, Radiometer Medical A/S). Demographics, and anthropometry were collected. ANOVA and linear regression were used to identify predictors. Reproducibility was assessed by intersubject coefficient of variation., Results: Age was a consistent predictor in all models; body size or fat and lean mass were important predictors in 3 of the models - STS peak force, STS peak power, and JMP peak power. STS was the most reproducible maneuver (average coefficient of variation =15.7%). Distracted body sway testing was not appropriate in these youngsters., Conclusion: The novel data presented in this study demonstrate a clear age (developmental) effect without any effect of sex on muscle function and postural control in young children. Lean muscle mass was important in some models (STS peak force and JMP peak power). The STS test was the best of the 4 maneuvers.

The 2007 to 2009 Canadian Health Measures Survey reported vitamin D status in a representative sample of Canadians (6-79 y); however, children <6 y were not assessed. Our objective was to measure vitamin D intake from food and supplements, sun exposure, and biological vitamin D status of children ages 2 through 5 y in Montréal (latitude 45°N). Preschoolers (n = 508) were recruited between June 2010 and 2011 in a random sample of licensed daycares in the regions of greater Montréal, Canada in a cross-sectional study. The total plasma 25-hydroxyvitamin D [25(OH)D] concentration was measured using a chemiluminescence assay (Liaison, Diasorin). Dietary intake was assessed during one 24-h period plus a 30-d FFQ. Socioeconomic, demographic, anthropometry, and sun exposure data were collected. Plasma 25(OH)D was ≥50 nmol/L in 88% of children, whereas 49.4% had concentrations ≥75 nmol/L during the 1-y study. Almost 95% of preschoolers had vitamin D intakes less than the Estimated Average Requirement (EAR), and 4.8% of preschoolers ≤3.9 y and 25.9% of preschoolers ≥4 y had calcium intakes less than the EAR. Plasma 25(OH)D was different across age, income, sun index, milk intake, and dietary and supplemental vitamin D intake tertiles. Despite vitamin D intakes less than the EAR, the vitamin D status of Montréal preschoolers attending daycare is mostly satisfactory even in winter, suggesting that the EAR value is too high in the context of typical exogenous intakes of vitamin D in North America.

The mechanisms underlying the selective death of substantia nigra (SN) neurons in Parkinson disease (PD) remain elusive. While inactivation of DJ-1, an oxidative stress suppressor, causes PD, animal models lacking DJ-1 show no overt dopaminergic (DA) neuron degeneration in the SN. Here, we show that aging mice lacking DJ-1 and the GDNF-receptor Ret in the DA system display an accelerated loss of SN cell bodies, but not axons, compared to mice that only lack Ret signaling. The survival requirement for DJ-1 is specific for the GIRK2-positive subpopulation in the SN which projects exclusively to the striatum and is more vulnerable in PD. Using Drosophila genetics, we show that constitutively active Ret and associated Ras/ERK, but not PI3K/Akt, signaling components interact genetically with DJ-1. Double loss-of-function experiments indicate that DJ-1 interacts with ERK signaling to control eye and wing development. Our study uncovers a conserved interaction between DJ-1 and Ret-mediated signaling and a novel cell survival role for DJ-1 in the mouse. A better understanding of the molecular connections between trophic signaling, cellular stress and aging could uncover new targets for drug development in PD., Competing Interests: The authors have declared that no competing interests exist.

Periphilin is involved in multiple processes in vivo. To explore its physiological role from an organismic perspective, we generated mice with a gene trap insertion in the periphilin-1 gene. Based on beta-gal reporter activity, a widespread periphilin expression was evident, especially in the developing somites and limbs, the embryonic nervous system, and the adult brain. In accordance with this broad expression, homozygous deficiency of periphilin was lethal in early embryogenesis. Mice with a heterozygous deficiency did not show any abnormalities of brain morphology and function, neither histologically nor regarding the transcriptome. Interestingly, the reduction of the periphilin-1 gene dosage was compensated by an increased expression of the remaining wild-type allele in the brain. These results point to an indispensable function of periphilin during murine development and an important role in the nervous system, reflected by a strong and tightly regulated expression in the murine brain., ((c) 2009 Wiley-Liss, Inc.)

The Parkinson's disease (PD)-associated gene DJ-1 mediates direct neuroprotection. The up-regulation of DJ-1 in reactive astrocytes also suggests a role in glia. Here we show that DJ-1 regulates proinflammatory responses in mouse astrocyte-rich primary cultures. When treated with a Toll-like receptor 4 agonist, the bacterial endotoxin lipopolysaccharide (LPS), Dj-1-knockout astrocytes generated >10 times more nitric oxide (NO) than littermate controls. Lentiviral reintroduction of DJ-1 restored the NO response to LPS. The enhanced NO production in Dj-1(-/-) astrocytes was mediated by a signaling pathway involving reactive oxygen species leading to specific hyperinduction of type II NO synthase [inducible NO synthase (iNOS)]. These effects coincided with significantly increased phosphorylation of p38 mitogen-activated protein kinase (MAPK), and p38(MAPK) inhibition suppressed NO production and iNOS mRNA and protein induction. Dj-1(-/-) astrocytes also induced the proinflammatory mediators cyclooxygenase-2 and interleukin-6 significantly more strongly, but not nerve growth factor. Finally, primary neuron cultures grown on Dj-1(-/-) astrocytes became apoptotic in response to LPS in an iNOS-dependent manner, directly demonstrating the neurotoxic potential of astrocytic DJ-1 deficiency. These findings identify DJ-1 as a regulator of proinflammatory responses and suggest that loss of DJ-1 contributes to PD pathogenesis by deregulation of astrocytic neuroinflammatory damage.

Mutations in the PARK7 gene encoding DJ-1 cause autosomal recessive Parkinson disease. The most deleterious point mutation is the L166P substitution, which resides in a structure motif comprising two alpha-helices (G and H) separated by a kink. Here we subjected the C-terminal helix-kink-helix motif to systematic site-directed mutagenesis, introducing helix-incompatible proline residues as well as conservative substitutions into the helical interface. Furthermore, we generated deletion mutants lacking the H-helix, the kink, and the entire C terminus. When transfected into neural and nonneural cell lines, steady-state levels of G-helix breaking and kink deletion mutants were dramatically lower than wild-type DJ-1. The effects of H-helix breakers were comparably smaller, and the non-helix breaking mutants only slightly destabilized DJ-1. The decreased steady-state levels were due to accelerated protein degradation involving in part the proteasome. G-helix breaking DJ-1 mutations abolished dimer formation. These structural perturbations had functional consequences on the cytoprotective activities of DJ-1. The destabilizing mutations conferred reduced cytoprotection against H(2)O(2) in transiently retransfected DJ-1 knock-out mouse embryonic fibroblasts. The loss of survival promoting activity of the DJ-1 mutants with destabilizing C-terminal mutations correlated with impaired anti-apoptotic signaling. We found that wild-type, but not mutant DJ-1 facilitated the Akt pathway and simultaneously blocked the apoptosis signal-regulating kinase 1, with which DJ-1 interacted in a redox-dependent manner. Thus, the G-helix and kink are critical determinants of the C-terminal helix-kink-helix motif, which is absolutely required for stability and the regulation of survival-promoting redox signaling of the Parkinson disease-associated protein DJ-1.

Mutations of NPHS1, the gene encoding the kidney glomerular filtration barrier protein nephrin, cause congenital nephrotic syndrome of the Finnish type. Nephrin is a component of the interpodocyte-spanning slit diaphragm: it mediates outside-in signaling and forms a nexus for homo- and heterotypic molecular interactions. When studying the nephrin-deficient mouse line generated by random insertional mutagenesis we unexpectedly discovered an endogenous antisense transcript originating from the nephrin-encoding locus. Further evidence of the antisense transcript (Nphs1as) was obtained by searching for Nphs1-like expressed sequence tags. Surprisingly, one clone showed exact complementarity in the antisense orientation. Nphs1as is expressed in the brain, thymus, and peripheral lymph nodes as well as in the embryonic stem cells. However, the mesenteric lymph nodes and the main sites of nephrin expression, the kidney and pancreas, were negative. Nphs1as is a continuous, polyadenylated mRNA that spans Nphs1 exons from 7 to 12 in the reverse orientation. The relative amounts of sense and antisense mRNAs as well as nephrin protein were determined by semiquantitative RT-PCR and immunoblotting, respectively, in various mouse tissues. These results suggest that Nphs1as may be important for the regulation of the appropriate tissue- and cell-type-specific expression of nephrin.