Computer-Aided Reconstruction and Application of Bacillus halodurans S7 Xylanase with Heat and Alkali Resistance.

ß-1,4-Endoxylanase is the most critical hydrolase for xylan degradation during lignocellulosic biomass utilization. However, its poor stability and activity in hot and alkaline environments hinder its widespread application. In this study, BhS7Xyl from Bacillus halodurans S7 was improved using a computer-aided design through isothermal compressibility (ßT) perturbation engineering and by combining three thermostability prediction algorithms (ICPE-TPA). The best variant with remarkable improvement in specific activity, heat resistance (70 °C), and alkaline resistance (both pH 9.0 and 70 °C), R69F/E137M/E145L, exhibited a 4.9-fold increase by wild-type in specific activity (1368.6 U/mg), a 39.4-fold increase in temperature half-life (458.1 min), and a 57.6-fold increase in pH half-life (383.1 min). Furthermore, R69F/E137M/E145L was applied to the hydrolysis of agricultural waste (corncob and hardwood pulp) to efficiently obtain a higher yield of high-value xylooligosaccharides. Overall, the ICPE-TPA strategy has the potential to improve the functional performance of enzymes under extreme conditions for the high-value utilization of lignocellulosic biomass.

Polyherbal extract improves glycometabolic control in alloxan-induced diabetic rats via down-regulating the MAPK/JNK pathway, modulating Nrf-2/Keap-1 expression, and stimulating insulin signaling.

Objectives: This study focused on the evaluation of antioxidant and antidiabetic activities of polyherbal extract (PHE), containing Cassia absus (L.), Gymnema sylvestre (R. Br.), Nigella sativa (L.), and Piper nigrum (L.), in alloxan-induced diabetes model. Materials and Methods: In vitro, HPLC characterization, DPPH scavenging assay, and α-amylase inhibition test were conducted. In vivo, acute oral toxicity of PHE was assessed. Alloxan-induced diabetic Wistar rats (n=6) were orally treated with PHE (200, 400, and 600 mg/kg/day) and glibenclamide (GLB; 10 mg/kg/day) for six consecutive weeks. Then, biochemical biomarkers, oxidative stress parameters, histopathological examination, and mRNA expression levels (RT-qPCR) were determined. Results: The presence of polyphenols in PHE was confirmed in correlation to marked DPPH scavenging (IC50: 1.60 mg/ml) and α-amylase inhibition (IC50: 0.82 mg/ml). PHE demonstrated no toxicity in rats up to a dose of 2000 mg/kg. In diabetic rats, PHE dose-dependently ameliorated the serum levels of glucose, insulin, glycated hemoglobin A1c (HbA1c), leptin, and glucokinase (GCK). Also, PHE substantially alleviated serum inflammatory markers (TNF-α and CRP) and oxidative stress indicators (MDA, SOD, and CAT) in pancreatic tissues. PHE, particularly at 600 mg/kg, attenuated cellular oxidative stress via modulating the mRNA expression levels of genes regulating MAPK/JNK (Mapk-8, Traf-4, and Traf-6) and Nrf-2/Keap-1 pathways and promoted insulin signaling through up-regulating insulin signaling cascade (Pdx-1, Ins-1, and Ins-2), as compared to GLB. Furthermore, histopathological findings supported the aforementioned results. Conclusion: Our study suggests that polyherbal extract has promising antioxidant and antidiabetic activities by modulating the MAPK/JNK, Nrf-2/Keap-1, and insulin signaling pathways.

Directed Evolution of the UDP-Glycosyltransferase UGTBL1 for Highly Regioselective and Efficient Biosynthesis of Natural Phenolic Glycosides.

The O-glycosylation of polyphenols for the synthesis of glycosides has garnered substantial attention in food research applications. However, the practical utility of UDP-glycosyltransferases (UGTs) is significantly hindered by their low catalytic efficiency and suboptimal regioselectivity. The concurrent optimization of the regioselectivity and activity during the glycosylation of polyphenols presents a formidable challenge. Here, we addressed the long-standing activity-regioselectivity tradeoff in glycosyltransferase UGTBL1 through systematic enzyme engineering. The optimal combination of mutants, N61S/I62M/D63W/A208R/P218W/R282W (SMWRW1W2), yielded a 6.1-fold improvement in relative activity and a 17.3-fold increase in the ratio of gastrodin to para-hydroxybenzyl alcohol-4'-O-ß-glucoside (with 89.5% regioselectivity for gastrodin) compared to those of the wild-type enzyme and ultimately allowed gram-scale production of gastrodin (1,066.2 mg/L) using whole-cell biocatalysis. In addition, variant SMWRW1W2 exhibited a preference for producing phenolic glycosides from several substrates. This study lays the foundation for the engineering of additional UGTs and the practical applications of UGTs in regioselective retrofitting.

Core-shell design of UiO66-Fe3O4 configured with EDTA-assisted washing for rapid adsorption and simple recovery of heavy metal pollutants from soil.

The coupling of washing with adsorption process can be adopted for the treatment of soils contaminated with heavy metals pollution. However, the complex environment of soil and the competitive behavior of leaching chemicals considerably restrain adsorption capacity of adsorbent material during washing process, which demands a higher resistance of the adsorbents to interference. In this study, we synthesized strongly magnetic, high specific surface area (573.49 m2/g) UiO66 composites (i.e., UiO66-Fe3O4) using hydrothermal process. The UiO66-Fe3O4 was applied as an adsorbent during the ethylene diamine tetraacetic acid (EDTA)-assisted washing process of contaminated soil. The incorporation of UiO66-Fe3O4 results in rapid heavy metal removal and recovery from the soil under low concentrations of washing agent (0.001 mol/L) with reduced residual heavy metal mobility of soil after remediation. Furthermore, UiO66-Fe3O4 can quickly recollect by an external magnet, which offers a simple and inexpensive recovery method for heavy metals from contaminated soil. Overall, UiO66-Fe3O4 configuration with EDTA-assisted washing process showed opportunities for heavy metals contaminated sites.

Bacterial diversity of stingless bee honey in Yunnan, China: isolation and genome sequencing of a novel acid-resistant Lactobacillus pentosus (SYBC-MI) with probiotic and L. tryptophan producing potential via millet fermentation.

Stingless bee (Hymenoptera, Apidae, and Trigona) honey is a remarkable "miracle liquid" with a wide range of medical benefits for conditions including gastroenteritis, cataracts, and wound healing. Our study aimed to isolate, identify, and characterize acid-resistant Lactobacillus spp. from sour honey distributed in Yunnan, China. To assess the safety of an entirely novel Lactobacillus pentosus strain, S4 (OM618128), based on probiotic property evaluation and whole-genome sequencing analysis. A 16S rRNA gene high-throughput sequencing analysis showed that Lactobacillus was abundant at the genus level in sour honey. Seven Lactobacillus strains (viz. S1-7) were isolated from sour honey using a multiple-anaerobic culture enrichment method. One potential acid-resistant isolate, Lactobacillus sp. S4, was obtained after screening the seven Lactobacillus isolates, and it had the highest lactic acid production (17.62 g/L), followed by Lactobacillus sp. S3 (17.07 g/L). Phylogenetic and comparative analyses of conserved sequence regions have shown that all seven strains are phylogenetically located in the Lactobacillus pentosus sub-cluster. In L. pentosus SYBC-MI, there is a circular chromosome (3288615 bps) and 11,466 bps plasmids. GC content is 44.03%. The number of predicted genes is 3,129, with 16 rRNAs and 74 tRNAs present. During the fermentation of foxtail millet by seven Lactobacillus pentosus (S1-7) strains isolated from sour honey, a potential tryptophan accumulating isolate, Lactobacillus pentosus S4, was obtained, which could reach a maximum tryptophan content of 238.43 mgL-1 that is 1.80 times the initial tryptophan content in the fermentation broth. This strain has strong acid tolerance, salt tolerance, and fermentation acid production abilities. This strain degrades nitrite at a rate of over 99%, and it has high probiotic potential as well. This project has established a solid foundation for further exploring the excellent lactic acid bacteria in sour honey. It is also investigating the key taxa and their role in the environment. According to the results of our studies, these LAB isolates provide a lot of potential for use in the future, as a source of probiotics for human, animals, and starter cultures for food applications.

Phytochemical analysis and gastroprotective effect of Stellaria media (L.) Vill. methanolic extract on piroxicam-induced gastric ulcer in Wistar rats.

Stellaria media L. has traditionally been used to treat inflammatory and gastrointestinal ailments. This study aimed to phytochemically characterize the S. media extract and explore its anti-ulcer efficacy against piroxicam-induced stomach lesions in Wistar rats. Phytochemical analysis was performed and antioxidant capacity of extract was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. In vivo, piroxicam (30mg/kg) was administered to induce gastric ulceration. Gastro protective effect of S. media extract was observed at 150, 300 and 450mg/kg, respectively. While omeprazole (20mg/kg) was used as a conventional anti-ulcer drug. After oral treatment for 14 days, stomach acidic secretions, ulcerogenic indices, hematological markers and oxidative stress parameters were assessed along with histological examination. The existence of polyphenol contents in S. media extract was confirmed in correlation to a marked DPPH inhibition (IC50 27.94µg/mL). S. media extract resulted in a dose-dependent elevation in gastric pH while a decrease in acid volume, acidity and ulceration. Also, S. media extract administration restored the impaired hematological markers (RBCs, Hb, WBCs and PLTs) and decreased oxidative stress by reducing oxidants (TOS and MDA) while raising antioxidants (TAC and CAT). Furthermore, gastric histological results corroborated the aforementioned findings. Conclusively, S. media could provide a promising protective effect against drug-induced gastric ulceration.

Curcumin Co-Encapsulation Potentiates Anti-Arthritic Efficacy of Meloxicam Biodegradable Nanoparticles in Adjuvant-Induced Arthritis Animal Model.

This study aimed to evaluate the anti-arthritic activity of curcumin and meloxicam co-loaded PLGA nanoparticles in adjuvant-induced arthritic rats. PLGA nanoparticles encapsulating curcumin (nCur) and meloxicam (nMlx) alone and in combination (nCur/Mlx) were used to characterize zeta size and potential, polydispersity index, encapsulation efficiency (%), compound-polymer interactions (FT-IR analysis), and surface morphology (SEM imaging). In vivo, Complete Freund's adjuvant-induced arthritic rats were intraperitoneally (i.p.) administered with curcumin, meloxicam, curcumin plus meloxicam, nCur, nMlx, and nCur/Mlx for 28 consecutive days. Results showed that nCur, nMlx, and nCur/Mlx significantly (p ≤ 0.05) reduced paw swelling and arthritic score, restored body weight and the immune organ index (thymus and spleen), as well as attenuated serum inflammatory markers (RF, CRP, and PGE2) and oxidative stress parameters (MDA, SOD, and CAT) in adjuvant-induced arthritic rats compared to free compounds. In addition, mono- and dual-compound-loaded nanoparticles significantly (p ≤ 0.05) down-regulated pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), up-regulated anti-inflammatory cytokines (IL-4, IL-10, and IFN-γ), and modulated OPG and RANKL expressions in paw tissue. The aforementioned results were further confirmed through radiological and histopathological examinations. Furthermore, the anti-arthritic effect of nCur/Mlx was notably (p ≤ 0.05) enhanced compared to nCur or nMlx alone. In conclusion, the co-nanoencapsulation of curcumin could potentiate the anti-arthritic activity of meloxicam and could provide a novel therapeutic approach for the formulation of nanocarrier pharmaceutical products for the management of arthritis.

Anti-Pyretic, Analgesic, and Anti-Inflammatory Activities of Meloxicam and Curcumin Co-Encapsulated PLGA Nanoparticles in Acute Experimental Models.

Herein, we evaluated the in vivo effects of meloxicam and curcumin co-encapsulated PLGA nanoparticles in experimental acute models of pyrexia, nociception, and inflammation. Seven groups (n = 6) were designed for each investigation and pretreated intraperitoneally (i.p.): the control group, meloxicam (4 mg/kg b.w.), curcumin (15 mg/kg b.w.), and equivalent content containing PLGA capped nanoparticles of meloxicam (Mlx-NP) and curcumin (Cur-NP) alone and in combination (Mlx-Cur-NP; at two doses). The results showed that PLGA encapsulation significantly (p ≤ 0.05) improved the in vivo activities of each compound. Furthermore, co-encapsulation of meloxicam and curcumin potentiated the anti-pyretic effect on yeast-induced pyretic rats, anti-nociceptive effect on nociception induced in rats by formalin and heat, and anti-edematogenic activity in xylene-induced ear edema in rats in a dose-dependent manner. In carrageenan-induced paw inflammation in rats, meloxicam and curcumin co-loading (Mlx-Cur-NP) resulted in significant (p ≤ 0.05) inhibition of paw inflammation, reduction in TNF-α and PGE2 levels, downregulation of expressions of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), as well as a decrease in histopathological changes and TNF-α immunoexpression in paw tissues. Moreover, Mlx-Cur-NP demonstrated noteworthy potentiation in pharmacological effects compared to free compounds and mono-compound-loaded nanoparticles. Thus, the association of meloxicam with curcumin in a biodegradable nanocarrier system could provide a promising anti-pyretic, anti-nociceptive, and anti-inflammatory therapeutic approach for acute conditions.

How to Train Your Posture: Haptic Feedback Can be Used for Postural Adaptation of the Trunk During Upper-Limb Motor Training.

Poor trunk posture, especially during long periods of sitting, could lead to problems such as Low Back Pain (LBP) and Forward Head Posture (FHP). Typical solutions are based on visual or vibration-based feedback. However, these systems could lead to feedback being ignored by the user and phantom vibration syndrome, respectively. In this study, we propose using haptic feedback for postural adaptation. In this two-part study, twenty-four healthy participants (age 25.87 ± 2.17 years) adapted to three different postural targets in the anterior direction while performing a unimanual reaching task using a robotic device. Results suggest a strong adaptation to the desired postural targets. Mean anterior trunk bending after the intervention is significantly different compared to baseline measurements for all postural targets. Additional analysis of movement straightness and smoothness indicates an absence of any negative interference of posture-based feedback on the performance of reaching movement. Taken together, these results suggest that haptic feedback-based systems could be used for postural adaptation applications. Also, this type of postural adaptation system can be used during the rehabilitation of stroke patients to reduce trunk compensation in lieu of typical physical constraint-based methods.

Bacterial metabolic engineering for the production of second-generation (2 G) bioethanol and biobutanol; a review.

The second generation (2 G) biofuels were introduced to solve the issues associated with first-generation biofuel (dependency on food materials) and fossil fuels, such as reservoirs diminution, high demand, price fluctuation, and lethal greenhouse gases emission. Butanol and ethanol are the main 2 G biofuels. They are used as a disinfectant, antiseptic, and chemical solvent in the pharmaceutical, plastic, textiles, cosmetics, and fuel industries. Currently, their bacterial biological production from lignocellulosic material at the industrial level with primitive microorganisms is under development and not economical and qualitative compatible as compared to that of fossil origin, due to the slow growth rate, low titer, recalcitrant nature of lignocellulose, strain intolerance to a higher amount of butanol and ethanol, and strain inability to tolerate inhibitors accumulated during pretreatment of lignocellulosic materials. Therefore, metabolic engineering strategies such as redirection of carbon flux, knocking out competing pathways, enhancing strain robustness and wide range of substrate utilization ability, and overexpression of enzymes involved in their biological synthesis have been applied to bacteria for enhancing their ability for 2 G ethanol and butanol production in a highly cost-effective amount from lignocellulosic materials. Herein, we summarized and reviewed the progress in metabolic engineering of bacterial species such as Clostridium spp,Escherichia coli, and Zymomonas mobilis for the synthesis of 2 G butanol and ethanol, especially from lignocellulosic materials.

Let the force guide you: a performance-based adaptive algorithm for postural training using haptic feedback.

Motor learning is an essential component of human behavior. Many different factors can influence the process of motor learning, such as the amount of practice and type of feedback. Changes in task difficulty during training can also considerably impact motor learning. Typical motor learning studies include a sequential variation of task difficulty, i.e., easy to challenging, irrespective of user performance. However, many studies have reported the importance of performance-based task difficulty variation for effective motor learning and skill transfer. A performance-based adaptive algorithm for task difficulty variation based on the challenge-point framework is proposed in this study. The algorithm is described for postural adaptation during simultaneous upper-limb training. Ten healthy participants (28 ± 2.44 years) were recruited to validate the algorithm. Participants adapted to a postural target of 20° in the anterior direction from the initial upright posture while performing a unimanual reaching task using a robotic device. Results suggest a significant decrease in postural error after training. The algorithm successfully adapted the task difficulty based on the performance of the user. The proposed algorithm could be modified for different motor skills and can be further evaluated for different applications in order to maximize the potential benefits of rehabilitation sessions.

How to work up an adult patient with metabolic acidosis.

Metabolic acidosis is a common complication among acutely unwell hospitalised patients. Untreated, it can result in undesirable cardiovascular, respiratory and neurological consequences. Metabolic acidosis can occur as an isolated entity or coexist with other acid-base disorders, making diagnosing the aetiology difficult. Accurate identification of the underlying cause is imperative for proper and timely management. A systematic approach can help simplify the assessment of patients and can aid in establishing the correct diagnosis, even in more complex cases. This article provides a practical, step-by-step guide for the assessment of adult patients with metabolic acidosis.

Haptic feedback system for postural adaptation during robotic rehabilitation of upper limb.

Although trunk compensation during stroke rehabilitation is widely studied, the proposed solutions primarily include a trunk constraint, which has several disadvantages. In this study, we have proposed a haptic feedback-based system for postural training during upper-limb motor rehabilitation. We have tested the proposed system on six healthy people in this preliminary study. Participants performed a simple 1-dimensional reaching task while their posture was being monitored. They received haptic feedback based on their trunk posture. Preliminary results revealed a significant decline in postural error (p<0.05) after the haptic-based training. The reduction in error was maintained even after haptic feedback was turned off. This study shows that haptic feedback could be a viable alternative to the traditional constraint-based methods for postural adaptation. Additional studies need to be conducted to further evaluate the influence of using such feedback strategies.

One-pot synthesis of sodium-doped willow-shaped graphitic carbon nitride for improved photocatalytic activity under visible-light irradiation.

Graphitic carbon nitride (g-C3N4) is considered as a promising low-cost polymeric semiconductor as conjugated photocatalyst for energy and environmental application. This study exhibits a Na-doped g-C3N4 with willow-leaf-shaped structure and high degree of crystallinity, which was synthesized with a convenient thermal polymerization using sodium carbonate (Na2CO3) as the sodium source. The π-conjugated systems of g-C3N4 were improved by doping sodium, which could accelerate the electron transport efficiency resulting in outstanding photocatalytic properties. Furthermore, optimum Na-doped g-C3N4 (CN-0.05) attributed its enhanced irradiation efficiency of light energy to its narrower band gap and significant improvement in charge separation. Consequently, the H2 evolution rate catalyzed with CN-0.05 can achieve 3559.8 µmol g-1 h-1, which is about 1.9 times higher than that with pristine g-C3N4. The rate of CN-0.05 for reduction of CO2 to CO (3.66 µmol g-1 h-1) is 6.6 times higher than that of pristine g-C3N4. In experiments of pollutants degradation, the reaction constants of degradation of rhodamine B (RhB) and methyl orange (MO) with CN-0.05 were 0.0271 and 0.0101 min-1, respectively, which are 4.7 and 7.2 times more efficient than pristine g-C3N4, respectively. This work provides a simple preparation method for tailoring effective photocatalyst for the sustainable solution of environmental issues.

Photocatalytic CO2 Reduction Using TiO2-Based Photocatalysts and TiO2 Z-Scheme Heterojunction Composites: A Review.

Photocatalytic CO2 reduction is a most promising technique to capture CO2 and reduce it to non-fossil fuel and other valuable compounds. Today, we are facing serious environmental issues due to the usage of excessive amounts of non-renewable energy resources. In this aspect, photocatalytic CO2 reduction will provide us with energy-enriched compounds and help to keep our environment clean and healthy. For this purpose, various photocatalysts have been designed to obtain selective products and improve efficiency of the system. Semiconductor materials have received great attention and have showed good performances for CO2 reduction. Titanium dioxide has been widely explored as a photocatalyst for CO2 reduction among the semiconductors due to its suitable electronic/optical properties, availability at low cost, thermal stability, low toxicity, and high photoactivity. Inspired by natural photosynthesis, the artificial Z-scheme of photocatalyst is constructed to provide an easy method to enhance efficiency of CO2 reduction. This review covers literature in this field, particularly the studies about the photocatalytic system, TiO2 Z-scheme heterojunction composites, and use of transition metals for CO2 photoreduction. Lastly, challenges and opportunities are described to open a new era in engineering and attain good performances with semiconductor materials for photocatalytic CO2 reduction.

Antipyretic and antinociceptive potential of Ricinus communis L. and Withania somnifera L. hydroalcoholic extracts in Wistar rats: A comparative study.

The present study was designed to evaluate the antipyretic and antinociceptive activities of R. communis leaves and W. somnifera roots hydroalcoholic extracts in Wistar rats. To assess the antipyretic activity, Brewer's yeast suspension was used to induce hyperthermia. Antinociceptive activity was observed using acetic acid-induced abdominal writhing, formalin-induced paw licking reflex and heat-induced pain models. R. communis and W. somnifera extracts were used at 150, 250 and 500mg/kg. Results showed that administration of both plants significantly (p<0.001) lowered rectal temperature (°C) in a dose-dependent manner from 1h to 4h of study. R. communis and W. somnifera extracts showed a dose-dependent reduction in abdominal writhing induced by acetic acid and decreased the paw licking reflex in formalin-induced nociceptive response. In the heat test, R. communis and W. somnifera extracts exhibited significant (p<0.001) analgesic effects evidenced as an increase in latency time. However, R. communis exhibited prominent antipyretic and antinociceptive activities at 250 and 500mg/kg as compared to W. somnifera. Conclusively, R. communis and W. somnifera could be a potential source of antipyretic and analgesic agents which require further studies.

Anti-arthritic activity of Ricinus communis L. and Withania somnifera L. extracts in adjuvant-induced arthritic rats via modulating inflammatory mediators and subsiding oxidative stress.

OBJECTIVES: This study aimed to evaluate the anti-arthritic activity of Ricinus communis leaves' and Withania somnifera roots' hydroalcoholic extracts in Complete Freund's adjuvant-induced arthritis in Wistar rats. MATERIALS AND METHODS: HPLC and FT-IR analysis detected pharmacologically important phytocompounds in both plant extracts. Oral treatments including methotrexate (MTX; 3 mg/kg twice a week) and extracts at 250 and 500 mg/kg/day were initiated after arthritis induction. Changes in paw swelling, arthritic score, body weight, organ indices (thymus and spleen), hematological and biochemical parameters, and pro-/anti-inflammatory cytokine expression using qRT-PCR were assessed. Oxidative stress markers in hepatic tissue were determined. Histopathological and radiological examinations were also performed. RESULTS: RCE (R. communis extract) and WSE (W. somnifera extract) demonstrated a reduction in paw swelling, arthritic score, and restoration of body weight and organ indices. Hematological parameters, serum inflammatory markers such as CRP and RF, and liver function markers of arthritic rats were significantly (P<0.01) ameliorated with RCE and WSE treatment. Both plants persuasively down-regulated IL-1ß, IL-6, IL-17a, TNF-α, and RANKL and up-regulated IL-4, INF-γ, and OPG relative expression as well as alleviating hepatic oxidative stress parameters. Histopathological and radiological findings revealed a marked reduction in tissue inflammation and bone erosion in extracts treated groups. CONCLUSION: The study findings suggest that R. communis leaves and W. somnifera roots have markedly subsided inflammation and improved health through modulating pro-/anti-inflammatory cytokine expression and reducing oxidative stress.

Robotic Assisted Upper Limb Training Post Stroke: A Randomized Control Trial Using Combinatory Approach Toward Reducing Workforce Demands.

Post stroke upper limb rehabilitation is a challenging problem with poor outcomes as 40% of survivors have functionally useless upper limbs. Robot-aided therapy (RAT) is a potential method to alleviate the effort of intensive, task-specific, repetitive upper limb exercises for both patients and therapists. The present study aims to investigate how a time matched combinatory training scheme that incorporates conventional and RAT, using H-Man, compares with conventional training toward reducing workforce demands. In a randomized control trial (NCT02188628, www.clinicaltrials.gov), 44 subacute to chronic stroke survivors with first-ever clinical stroke and predominant arm motor function deficits were recruited and randomized into two groups of 22 subjects: Robotic Therapy (RT) and Conventional Therapy (CT). Both groups received 18 sessions of 90 min; three sessions per week over 6 weeks. In each session, participants of the CT group received 90 min of 1:1 therapist-supervised conventional therapy while participants of the RT group underwent combinatory training which consisted of 60 min of minimally-supervised H-Man therapy followed by 30 min of conventional therapy. The clinical outcomes [Fugl-Meyer (FMA), Action Research Arm Test and, Grip Strength] and the quantitative measures (smoothness, time efficiency, and task error, derived from two robotic assessment tasks) were independently evaluated prior to therapy intervention (week 0), at mid-training (week 3), at the end of training (week 6), and post therapy (week 12 and 24). Significant differences within group were observed at the end of training for all clinical scales compared with baseline [mean and standard deviation of FMA score changes between baseline and week 6; RT: Δ4.41 (3.46) and CT: Δ3.0 (4.0); p < 0.01]. FMA gains were retained 18 weeks post-training [week 24; RT: Δ5.38 (4.67) and week 24 CT: Δ4.50 (5.35); p < 0.01]. The RT group clinical scores improved similarly when compared to CT group with no significant inter-group at all time points although the conventional therapy time was reduced to one third in RT group. There were no training-related adverse side effects. In conclusion, time matched combinatory training incorporating H-Man RAT produced similar outcomes compared to conventional therapy alone. Hence, this study supports a combinatory approach to improve motor function in post-stroke arm paresis. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02188628.

Neurorehabilitation From a Distance: Can Intelligent Technology Support Decentralized Access to Quality Therapy?

Current neurorehabilitation models primarily rely on extended hospital stays and regular therapy sessions requiring close physical interactions between rehabilitation professionals and patients. The current COVID-19 pandemic has challenged this model, as strict physical distancing rules and a shift in the allocation of hospital resources resulted in many neurological patients not receiving essential therapy. Accordingly, a recent survey revealed that the majority of European healthcare professionals involved in stroke care are concerned that this lack of care will have a noticeable negative impact on functional outcomes. COVID-19 highlights an urgent need to rethink conventional neurorehabilitation and develop alternative approaches to provide high-quality therapy while minimizing hospital stays and visits. Technology-based solutions, such as, robotics bear high potential to enable such a paradigm shift. While robot-assisted therapy is already established in clinics, the future challenge is to enable physically assisted therapy and assessments in a minimally supervized and decentralized manner, ideally at the patient's home. Key enablers are new rehabilitation devices that are portable, scalable and equipped with clinical intelligence, remote monitoring and coaching capabilities. In this perspective article, we discuss clinical and technological requirements for the development and deployment of minimally supervized, robot-assisted neurorehabilitation technologies in patient's homes. We elaborate on key principles to ensure feasibility and acceptance, and on how artificial intelligence can be leveraged for embedding clinical knowledge for safe use and personalized therapy adaptation. Such new models are likely to impact neurorehabilitation beyond COVID-19, by providing broad access to sustained, high-quality and high-dose therapy maximizing long-term functional outcomes.

Lactoferrin Supplementation to Prevent Late-Onset Sepsis in Preterm Infants: A Meta-Analysis.

OBJECTIVE: This study aimed to systematically review and meta-analyze the role of lactoferrin supplementation to prevent late-onset sepsis (LOS) in preterm infants. STUDY DESIGN: Database search include PubMed, Web of Science, and Cochrane central for randomized clinical trial (RCTs). The Cochrane Grading of Recommendations Assessment, Development, and Evaluation methodology was used for summarizing the results. RESULTS: Ten RCTs involving 3,679 infants were included. Lactoferrin supplementation with or without probiotics decreased all LOS (relative risk [RR]: 0.56; 95% confidence interval [CI]: 0.36-0.86; I 2 = 58%; 10 studies; 3,470 subjects; level of evidence [LOE]: low) significantly. Similarly, lactoferrin supplementation without probiotics decreased all LOS (RR: 0.43; 95% CI: 0.29-0.62; I 2 = 0%; 8 studies; 1,209 subjects; LOE: moderate) significantly. Lactoferrin supplementation did not significantly reduce necrotizing enterocolitis (RR: 0.62; 95% CI: 0.29-1.33; I 2 = 43%; 6 studies; 3,079 subjects; LOE: low), all-cause mortality (RR: 0.74; 95% CI: 0.36-1.53; I 2 = 53%; 8 studies; 3,395 subjects; LOE: very low), bronchopulmonary dysplasia (RR: 1; 95% CI: 0.90-1.13; I 2 = 0%; 4 studies; 2,570 subjects; LOE: moderate), and threshold retinopathy of prematurity eligible for surgical treatment (RR: 0.61; 95% CI: 0.25-1.51; I 2 = 74%; 2 studies; 2,481 subjects; LOE: very low). CONCLUSION: Low to moderate quality evidence suggests that lactoferrin supplementation reduces LOS in preterm infants. Further research is needed to improve the certainty in the evidence.