Search

Introduction: Early post-transplant hyperglycemia (EPTH) is an independent risk factor for hospital readmissions, acute rejection, infections and developing post-transplant diabetes mellitus (PTDM). Close glycemic control is prudent in the early post-transplant period. The management of EPTH was evaluated among a cohort of kidney transplant recipients, who either received routine care (RC) or dedicated endocrine care (DEC). Methods: A retrospective analysis was conducted on kidney transplant recipients from 2019 to 2023. The impact of DEC on post-transplant glycemic control was investigated. Hospitalized patients receiving post-transplant insulin therapy were included. DEC involved at least twice-daily blood glucose (BG) assessment by an endocrinologist, while the RC received usual care. A mixed-model analysis was employed to assess differences in BG trajectories between DEC and RC over an eight-day period. Additionally, various glycemic control metrics were compared, including glucose variability, time-in-range for target BG, rates of hypoglycemia and response to hyperglycemia. Results: The cohort comprised 113 patients. In the DEC group, 91% had pre-transplant DM compared to 15% in the RC group (p < 0.001). Patients under DEC had higher baseline BG and glycated hemoglobin compared to those under RC (p < 0.001, for both). The DEC group displayed a lower trajectory of BG over time compared to the RC group (p = 0.002). Patients under DEC were more likely to receive insulin if BG measured above 200 mg/dL (66% vs. 46%) and displayed less below-range BG (p < 0.001). Conclusions: Management of EPTH by DEC improves glycemic outcomes in renal transplant recipients.

Abstract The aim of our study was to evaluate if the response to follicular GnRH agonist (GnRHa) trigger be used to predict intracycle ovarian response in GnRH antagonist cycles among women undergoing fertility preservation IVF. We conducted a prospective study of 146 GnRH antagonist oocyte pickup (OPU) cycles to evaluate GnRHa stimulation test (GAST). On day 2 of the cycle, basal E2 were measured, followed by injection of 0.2 mg GnRHa as part of the initial ovarian stimulation. 12 h later blood sampling was repeated (GAST E3). E2 response was used as test parameter. The major outcome was the number of mature cryopreserved oocytes. We found a linear correlation between both GAST E3 level and GAST E3/E2 ratio and number of M2 oocytes. ROC curve analysis of GAST E3, GAST E3/E2 ratio, AFC and day 3 FSH for > 15 M2 and 15 M2 oocytes, AUC value of 0.8. Patients with GAST E3 ≤ 384 pmol/l has 58.6% risk to obtain 708 pmol/l have 66% chance for freezing > 15 oocytes. The response to single GnRHa administration during GnRH antagonist cycle can be used as biomarker of ovarian reserve. This simple, widely available marker, which reflect the estradiol response of small follicles, might predict the response of the specific cycle, and can potentially be used to adjust the treatment dose. Trial registration number: 0304-20-ASF.

Abstract This prospective study aimed to test the ability of follicular GnRH agonist challenge test (FACT) to predict suboptimal response to GnRH agonist trigger, assessed by LH levels post ovulation trigger in non-medical oocyte cryopreservation program. The study included 91 women that underwent non-medical fertility preservation. On day two to menstrual cycle, blood tests were drawn (basal Estradiol, basal FSH, basal LH, Progesterone) and ultrasound (US) was performed. On that evening, the women were instructed to inject 0.2 mg GnRH agonist (FACT) and arrive for repeated blood workup 10–12 h later in the next morning, followed by a flexible antagonist protocol. LH levels on the morning after ovulation trigger were compared to FACT LH levels. The results demonstrated that LH levels following agonist ovulation trigger below 15IU/L occurred in 1.09% of cycles and were predicted by FACT, r = 0.57, p 42.70 IU/L would predict LH post trigger of more than 30 IU/L with 75% sensitivity and 70% specificity, AUC = 0.81. LH levels post trigger also displayed significant positive correlation to basal FSH (r = 0.35, p = 0.002) and basal LH (r = 0.54, p

Background: Eccentric muscle contractions elicit distinct physiological responses, including modulation of the cytokine profile. Although relevant for rehabilitation, the effect of eccentric muscle training on the immune system has never been investigated in multiple sclerosis (MS). Objectives: Examine the immediate cytokine response of interleukin-4 (IL-4), IL-6, IL-10, IL-17a, interferon-gamma, and tumor necrosis factor-alpha after a moderate eccentric training session in individuals with MS. Additionally, further investigate the association between systemic cytokine levels at rest and clinical measures of mobility and lower limb functional strength. Design: Observational study. Methods: The first session included blood sampling for baseline cytokine measures. Subsequently, the participant completed a battery of clinical assessments related to mobility and lower limb strength, that is, the Timed-Up-and-Go Test, Five-Repetition-Sit-to-Stand-Test (5STS), Four-Square-Step-Test, and Two-Minute-Walk-Test. The second session included the eccentric exercise training session, followed by a second blood sampling to assess the acute cytokine response to the eccentric training bout. This session comprised 10 exercises concentrating on the strength of the trunk and lower extremities. Results: Twenty-seven people with MS (pwMS), with a mean age of 40.1 years, participated in the study. No difference was demonstrated in the cytokine concentration values between baseline and immediately after the eccentric training session. The 5STS explained 30.3% of the variance associated with interferon-gamma, 14.8% with IL-4, and 13.8% with IL-10. Conclusion: An eccentric training bout does not impact cytokine concentration in the blood and, consequently, does not boost a pro-inflammatory response, thus, it can be performed on pwMS in a rehabilitation setting.

The escalating threat and impact of network-based attacks necessitate innovative intrusion detection systems. Machine learning has shown promise, with recent strides in quantum machine learning offering new avenues. However, the potential of quantum computing is tempered by challenges in current noisy intermediate-scale quantum era machines. In this article, we explore quantum neural networks (QNNs) for intrusion detection, optimizing their performance within current quantum computing limitations. Our approach includes efficient classical feature encoding, QNN classifier selection, and performance tuning leveraging current quantum computational power. This study culminates in an optimized multilayered QNN architecture for network intrusion detection. A small version of the proposed architecture was implemented on IonQ's Aria-1 quantum computer, achieving a notable 0.86 F1 score using the NF-UNSW-NB15 dataset. In addition, we introduce a novel metric, certainty factor, laying the foundation for future integration of uncertainty measures in quantum classification outputs. Moreover, this factor is used to predict the noise susceptibility of our quantum binary classification system.

Recently, much attention has been given to the development of various energy harvesting technologies to power remote electronic sensors, data loggers, and communicators that can be installed on smart grid systems. Magnetic energy harvesting is, perhaps, the most straightforward way to capture a significant amount of power from a current-carrying overhead line. Since the harvester is expected to have a small size, the high currents of the distribution system easily saturate its magnetic core. As a result, the operation of the magnetic harvester is highly nonlinear and makes precise analytical modeling difficult. The operation of an overhead line magnetic energy harvester (OLMEH) generating significant DC power output into a constant voltage load was investigated in this paper. The analysis method was based on the Froelich equation to analytically model the nonlinearity of the core’s BH characteristic. The main findings of this piecewise nonlinear analysis include a closed-form solution that accounts for both the core and rectifiers’ nonlinearities and provides an accurate prediction of OLMEH transfer window length, output current, and harvested power. Continuous and discontinuous operational modes are identified and the mode transition boundary is obtained quantitatively. The theoretical investigation was concluded by comparison with a computer simulation and also verified by the experimental results of a laboratory prototype harvester. A good agreement was found.

This paper presents an extension of a 5-level T-Type inverter to a high-power multi-level inverter that can be implemented in electric vehicles and trucks. The proposed inverter possesses several advantages over standard topologies such as Neutral Point Clamped, Flying Capacitor, and Cascaded H-bridge. The main advantages are a low number of components, an estimated lower price and weight, smaller dimensions, and the implementation of only one DC voltage source per phase. The proposed topology can be implemented for any required odd number of voltage levels. Due to the estimated reduced dimensions and weight, the proposed topology is especially suitable for electric transportation applications. The operation of the proposed topology was validated for 9- and 13-level configurations under PD, POD, and APOD PWMs. The simulation results show the inverter’s practicability for supplying motors of electric trucks.

Three-phase three-level AC/DC and DC/AC converters have demonstrated several advantages over their classical two-level counterparts such as better efficiency, enhanced total harmonic distortion, lower dv/dt and lesser overall chip area. T-type and neutral point clamped (NPC) topologies dominate the family of three-phase three-level converters, widely used in 10kVA – 100kVA power range. However, control of three-level converters is more complicated than of their classical two-level counterparts due to necessity of adopting an additional voltage loop, aimed to balance partial split DC link voltages. Moreover, the latter contain multiples of triple-base-frequency harmonic ripple even under balanced AC-side operation (this does not happen in two-level converters), which should be minimized by the balancing loop mentioned above. The nature of partial DC link ripple formation was analyzed in-depth for unity power factor operation, yet hardly extended to non-unity power factor cases. Moreover, inaccurate conclusions were drawn in some of the related studies. Consequently, this paper focuses on comprehensive modeling and formulation of split DC link capacitors balancing problem in three-phase three-level bidirectional AC/DC converters operating with arbitrary power factor. Analytical expression for dynamics of partial DC link voltages difference is derived and studied in depth. The relation between zero-sequence component of modulation signals and neutral point current, tending to unbalance partial DC link voltages is explicitly established for arbitrary power factor values. Practical cases of restricted and unrestricted zero-sequence component of modulation signals are presented. Analytical predictions are shown to be fully supported by simulations based on both switching-cycle-averaged and full switched converter models. Experimental results obtained employing a 10kVA T-type converter prototype operating with restricted zero-sequence component of modulation signals under different power factor values are also given to further validate the presented methodology.

Abstract Background Sperm banks face a continuously evolving gap between the increasing demand for sperm donation (SD) vs. limited available reserve. To improve donors’ recruitment and increase supply, motivations towards SD should be investigated specifically among young men who have the potential to become donors. Our aim was to evaluate factors which increase and decrease predisposition to donate sperm among non-donor students, who represent a “potential pool” for possible donors’ recruitment. Results Ninety-three men fulfilled the questionnaire with mean age of 28.2 ± 4.5 years. The most powerful incentive to donate sperm was financial reward followed by a willingness to help others to build a family (3.8 and 3.4, respectively). The most dominant consideration to decline donation was the fear of anonymity loss and future regret (4 and 3.8). While participants’ willingness for anonymous SD was fair (2.8), the open-identity donation was rated significantly lower (1.75, p

Abstract Background Epigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that greater polyphenol intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding with elevated urine polyphenols. The effect of polyphenol-rich dietary interventions on biological aging is yet to be determined. Methods We calculated different biological aging epigenetic clocks of different generations (Horvath2013, Hannum2013, Li2018, Horvath skin and blood2018, PhenoAge2018, PCGrimAge2022), their corresponding age and intrinsic age accelerations, and DunedinPACE, all based on DNA methylation (Illumina EPIC array; pre-specified secondary outcome) for 256 participants with abdominal obesity or dyslipidemia, before and after the 18-month DIRECT PLUS randomized controlled trial. Three interventions were assigned: healthy dietary guidelines, a Mediterranean (MED) diet, and a polyphenol-rich, low-red/processed meat Green-MED diet. Both MED groups consumed 28 g walnuts/day (+ 440 mg/day polyphenols). The Green-MED group consumed green tea (3–4 cups/day) and Mankai (Wolffia globosa strain) 500-ml green shake (+ 800 mg/day polyphenols). Adherence to the Green-MED diet was assessed by questionnaire and urine polyphenols metabolomics (high-performance liquid chromatography quadrupole time of flight). Results Baseline chronological age (51.3 ± 10.6 years) was significantly correlated with all methylation age (mAge) clocks with correlations ranging from 0.83 to 0.95; p

Objective: Deep brain stimulation (DBS) studies have shown that stimulation of the motor segment of the thalamus based on probabilistic tractography is predictive of improvement in essential tremor (ET). However, probabilistic methods are computationally demanding, requiring the need for alternative tractography methods for use in the clinical setting. The purpose of this study was to compare probabilistic vs deterministic tractography methods for connectivity-based targeting in patients with ET. Methods: Probabilistic and deterministic tractography methods were retrospectively applied to diffusion-weighted data sets in 36 patients with refractory ET. The thalamus and precentral gyrus were selected as regions of interest and fiber tracking was performed between these regions to produce connectivity-based thalamic segmentations, per prior methods. The resultant deterministic target maps were compared with those of thresholded probabilistic maps. The center of gravity (CG) of each connectivity map was determined and the differences in spatial distribution between the tractography methods were characterized. Furthermore, the intersection between the connectivity maps and CGs with the therapeutic volume of tissue activated (VTA) was calculated. A mixed linear model was then used to assess clinical improvement in tremor with volume of overlap. Results: Both tractography methods delineated the region of the thalamus with connectivity to the precentral gyrus to be within the posterolateral aspect of the thalamus. The average CG of deterministic maps was more medial-posterior in both the left (3.7 ± 1.3 mm3) and the right (3.5 ± 2.2 mm3) hemispheres when compared to 30 %-thresholded probabilistic maps. Mixed linear model showed that the volume of overlap between CGs of deterministic and probabilistic targeting maps and therapeutic VTAs were significant predictors of clinical improvement. Conclusions: Deterministic tractography can reconstruct DBS thalamic target maps in approximately 5 min comparable to those produced by probabilistic methods that require > 12 h to generate. Despite differences in CG between the methods, both deterministic-based and probabilistic targeting were predictive of clinical improvement in ET.

PurposeTo study the efficacy of orbital injections of triamcinolone acetonide mixed 1:1 with dexamethasone in the treatment of active thyroid eye disease.MethodsPatients that received orbital injection(s) of triamcinolone acetonide mixed 1:1 with dexamethasone for thyroid eye disease were included in this retrospective study. Demographic and clinical data were collected from the pre-treatment and 1 month follow up evaluations. Clinical data included subjective pain and diplopia scores, best-corrected visual acuity, Intraocular pressure, extraocular motility, clinical activity score, Hertel exophthalmometry, and upper eyelid margin to reflex distance.ResultsFifteen patients, 33 orbital injections, were included in the study. The average patient age was 59.2 years (SD ± 13.0) and 89% female. Subjectively, 67% of patients reported improvement of orbital pain and pressure versus 28% stable and 5% worse (p

ABSTRACTWe previously reported that autologous-fecal-microbiota-transplantation (aFMT), following 6 m of lifestyle intervention, attenuated subsequent weight regain and insulin rebound for participants consuming a high-polyphenol green-Mediterranean diet. Here, we explored whether specific changes in the core (abundant) vs. non-core (low-abundance) gut microbiome taxa fractions during the weight-loss phase (0–6 m) were differentially associated with weight maintenance following aFMT. Eighty-two abdominally obese/dyslipidemic participants (age = 52 years; 6 m weightloss = −8.3 kg) who provided fecal samples (0 m, 6 m) were included. Frozen 6 m’s fecal samples were processed into 1 g, opaque and odorless aFMT capsules. Participants were randomly assigned to receive 100 capsules containing their own fecal microbiota or placebo over 8 m-14 m in ten administrations (adherence rate > 90%). Gut microbiome composition was evaluated using shotgun metagenomic sequencing. Non-core taxa were defined as ≤ 66% prevalence across participants. Overall, 450 species were analyzed. At baseline, 13.3% were classified as core, and Firmicutes presented the highest core proportion by phylum. During 6 m weight-loss phase, abundance of non-core species changed more than core species (P

This article presents a generic approach to load-current THD minimization in hard-switched Staircase Modulation (SCM) based three-phase (3ɸ) Multilevel Inverters (MLI) with either fixed or variable DC source Ratios (DCR). First, a computer-aided closed-form analytical formulation of Weighted THD (WTHD) applied directly to line-voltage waveforms is derived using Maple software and then verified against numerically-obtained results of previous works. The proposed symbolic analysis of Weighted Line-voltage THD (WLTHD) applies to 3ɸ-MLIs of any topology with Equal Voltage Steps (EVS) or Unequal Voltage Steps (UVS), and any number of voltage levels count (N), either odd or even. Such an analytical approach eliminates the risk of underestimation errors associated with numerical methods. The proposed closed-form WLTHD expression is then utilized for optimal minimization of current-THD in 3ɸ inductive loads with unconnected neutral. This is achieved by introducing a generic UVS-based Optimal Minimization of WLTHD (OMWLTHD), which calculates the optimum Phase Switching Angles (PSA) and the supply DC-Ratios (DCR), given any desired Modulation Index (MI), thus ensuring minimum current-THD across the entire linear MI range. The revealed OMWLTHD approach is fully validated by both digital simulations and controller plus hardware-in-loop (C-HIL) based experiments, using 7-, 8-, and even 13-level 3ɸ-MLIs of both EVS and UVS configurations. Furthermore, to reveal the impact of WLTHD minimization on actual load current-THD, the MLIs were loaded by a Resistive-Inductive-EMF (RLE) load, as well as a 3ɸ squirrel cage induction motor, thus representing a wide range of possible loads, such as motors and ac grids. The conclusive verification results have shown that in the case of 3-wire inductive loads with a power factor up to 0.95, the proposed UVS-based WLTHD optimization is more beneficial for current-THD minimization over other harmonic distortion quantifying parameters, as WLTHD presents the strongest correlation to actual load current THD when tested against any other parameter such as phase and line THD or WTHD. The revealed improvement in current THD was even more pronounced for UVS-based SCM compared to traditional EVS-based SCM. Additionally, MATLAB and Maple source files of the proposed WLTHD formulations and Excel-based pre-calculated optimum PSA and DCR sets for different values of N are provided as downloadable links to further enhance the contribution of the article.

This preliminary study aimed to investigate an ActiGraft blood clot implant (RedDress Ltd., Pardes-Hanna, Israel) attempting to treat and induce the regeneration of a completely injured peripheral nerve with a massive loss defect. The tibial portion of the sciatic nerve in 11 rabbits was transected, and a 25 mm nerve gap was reconnected using a collagen tube. A comparison was performed between the treatment group (eight rabbits; reconnection using a tube filled with ActiGraft blood clot) and the control group (three rabbits; gap reconnection using an empty tube). The post-operative follow-up period lasted 18 weeks and included electrophysiological and histochemical assessments. The pathological severity score was high in the tube cross sections of the control group (1.33) compared to the ActiGraft blood clot treatment group (0.63). Morphometric analysis showed a higher percentage of the positive myelin basic protein (MBP) stained area in the ActiGraft blood clot group (19.57%) versus the control group (3.67%). These differences were not statistically significant due to the small group sizes and the large intra-group variability. The results of this preliminary study suggest that the application of an ActiGraft blood clot (into the collagen tube) can enable nerve recovery. However, a future study using a larger animal group is required to achieve objective statistical results.

BackgroundFasting morning cortisol (FMC) stress hormone levels, are suggested to reflect increased cardiometabolic risk. Acute response to weight loss diet could elevate FMC. Richer Polyphenols and lower carbohydrates diets could favor FMC levels. We aimed to explore the effect of long-term high polyphenol Mediterranean diet (green-MED) on FMC and its relation to metabolic health.MethodsWe randomized 294 participants into one of three dietary interventions for 18-months: healthy dietary guidelines (HDG), Mediterranean (MED) diet, and Green-MED diet. Both MED diets were similarly hypocaloric and lower in carbohydrates and included walnuts (28 g/day). The high-polyphenols/low-meat Green-MED group further included green tea (3-4 cups/day) and a Wolffia-globosa Mankai plant 1-cup green shakeFMC was obtained between 07:00-07:30AM at baseline, six, and eighteen-months.ResultsParticipants (age=51.1years, 88% men) had a mean BMI of 31.3kg/m2, FMC=304.07nmol\L, and glycated-hemoglobin-A1c (HbA1c)=5.5%; 11% had type 2 diabetes and 38% were prediabetes. Baseline FMC was higher among men (308.6 ± 90.05nmol\L) than women (269.6± 83.9nmol\L;p=0.02). Higher baseline FMC was directly associated with age, dysglycemia, MRI-assessed visceral adiposity, fasting plasma glucose (FPG), high-sensitivity C-reactive-protein (hsCRP), testosterone, Progesterone and TSH levels (p ≤ 0.05 for all). The 18-month retention was 89%. After 6 months, there were no significant changes in FMC among all intervention groups. However, after 18-months, both MED groups significantly reduced FMC (MED=-1.6%[-21.45 nmol/L]; Green-MED=-1.8%[-26.67 nmol/L]; p

Staircase Modulation (SCM) is a popular switching strategy for multilevel inverters (MLI), which is often a preferable alternative to Pulse Width Modulation (PWM) due to its reduced switching losses, especially for MLIs with a relatively high number of voltage levels (N). In some applications, such as motor drives, or when output filters are applicable, SCM may also suit MLIs with moderate N values. While MLIs with Equal DC Sources (EDCS) are more common, MLIs with Unequal DC Sources (UDCS), such as asymmetric Cascaded H-Bridge (CHB) MLIs are known to further reduce the waveforms’ Total Harmonic Distortion (THD). The main objective of SCM is to adjust the waveform’s fundamental component, while employing some harmonic mitigation strategy, such as THD minimization. Such an optimization approach relies on an accurate THD formulation, which eliminates underestimation errors associated with numerical THD approximations. This paper reveals novel generic analytical formulations of both Phase-voltage THD (PTHD) for single-phase MLIs and Line-voltage THD (LTHD) for three-phase MLIs. The revealed exact formulation approach is derived from Fourier series representation of THD, resulting in simple closed-form PTHD and LTHD expressions, applicable to any MLI topology, with either EDCS or UDCS configurations, and arbitrary value of N (odd and even). Given an arbitrary N value, the proposed formulations can be used to generate symbolic N-level PTHD or LTHD expressions, which are symbolic functions of the Phase Switching Angles (PSA) and (optionally) the DC source Ratios (DCR). The revealed THD formulations are verified and compared against recently introduced time-domain-based THD formulations. It is shown that when both time and frequency-based formulations are employed in THD minimizations to form a novel Hybrid Temporal-Spectral (HTS) Optimal Minimization of THD (OMTHD) approach, even better results can be achieved. The novel OMTHD is deeply explored and verified by both digital simulations and Controller + Hardware in Loop (C-HIL) based real-time experiments using 7- and 8-level three-phase MLI configurations. A downloadable supplemental file containing Maple and MATLAB functions of the proposed THD expressions, as well as pre-calculated sets of optimum variables for different values of N is provided for readers' convenience.

Abstract Background Mediterranean (MED) diet is a rich source of polyphenols, which benefit adiposity by several mechanisms. We explored the effect of the green-MED diet, twice fortified in dietary polyphenols and lower in red/processed meat, on visceral adipose tissue (VAT). Methods In the 18-month Dietary Intervention Randomized Controlled Trial PoLyphenols UnproceSsed (DIRECT-PLUS) weight-loss trial, 294 participants were randomized to (A) healthy dietary guidelines (HDG), (B) MED, or (C) green-MED diets, all combined with physical activity. Both isocaloric MED groups consumed 28 g/day of walnuts (+ 440 mg/day polyphenols). The green-MED group further consumed green tea (3–4 cups/day) and Wolffia globosa (duckweed strain) plant green shake (100 g frozen cubes/day) (+ 800mg/day polyphenols) and reduced red meat intake. We used magnetic resonance imaging (MRI) to quantify the abdominal adipose tissues. Results Participants (age = 51 years; 88% men; body mass index = 31.2 kg/m2; 29% VAT) had an 89.8% retention rate and 79.3% completed eligible MRIs. While both MED diets reached similar moderate weight (MED: − 2.7%, green-MED: − 3.9%) and waist circumference (MED: − 4.7%, green-MED: − 5.7%) loss, the green-MED dieters doubled the VAT loss (HDG: − 4.2%, MED: − 6.0%, green-MED: − 14.1%; p < 0.05, independent of age, sex, waist circumference, or weight loss). Higher dietary consumption of green tea, walnuts, and Wolffia globosa; lower red meat intake; higher total plasma polyphenols (mainly hippuric acid), and elevated urine urolithin A polyphenol were significantly related to greater VAT loss (p < 0.05, multivariate models). Conclusions A green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression. Trial registration ClinicalTrials.gov , NCT03020186

Background: Obesity is associated with dyslipidemia, and weight loss can improve obese patients’ lipid profile. Here, we assessed whether non-interventional weight changes are associated with alterations in lipid profile, particularly the triglyceride (TG)-to-high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C). Methods: In this retrospective analysis of subjects referred to medical screening, body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), TG, and HDL-C levels were measured annually. Patients were divided according to BMI changes between visits. The primary outcomes were the changes in LDL-C, TG, HDL-C, and the TG/HDL-C ratio between visits. Results: The final analysis included 18,828 subjects. During the year of follow-up, 9.3% of the study population lost more than 5% of their weight and 9.2% gained more than 5% of their weight. The effect of weight changes on TG and on the TG/HDL-C ratio was remarkable. Patients with greater BMI increases showed greater increases in their TG/HDL-C ratio, and conversely, a decreased BMI level had lower TG/HDL-C ratios. This is true even for moderate changes of more than 2.5% in BMI. Conclusions: Non-interventional weight changes, even modest ones, are associated with significant alterations in the lipid profile. Understanding that modest, non-interventional weight changes are associated with alterations in the TG/HDL-C ratio may aid in better risk stratification and primary prevention of CV morbidity and mortality.

It is essential to improve our understanding of the features that influence aggressiveness and invasion in high grade gliomas (HGG). Here, the authors characterize dynamic anatomical structures in HGG called oncostreams, which are associated with tumor growth and are regulated by COL1A1.

Background: Obesity negatively impacts multiple bodily systems, including the central nervous system. Retrospective studies that estimated chronological age from neuroimaging have found accelerated brain aging in obesity, but it is unclear how this estimation would be affected by weight loss following a lifestyle intervention. Methods: In a sub-study of 102 participants of the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS) trial, we tested the effect of weight loss following 18 months of lifestyle intervention on predicted brain age based on magnetic resonance imaging (MRI)-assessed resting-state functional connectivity (RSFC). We further examined how dynamics in multiple health factors, including anthropometric measurements, blood biomarkers, and fat deposition, can account for changes in brain age. Results: To establish our method, we first demonstrated that our model could successfully predict chronological age from RSFC in three cohorts (n=291;358;102). We then found that among the DIRECT-PLUS participants, 1% of body weight loss resulted in an 8.9 months’ attenuation of brain age. Attenuation of brain age was significantly associated with improved liver biomarkers, decreased liver fat, and visceral and deep subcutaneous adipose tissues after 18 months of intervention. Finally, we showed that lower consumption of processed food, sweets and beverages were associated with attenuated brain age. Conclusions: Successful weight loss following lifestyle intervention might have a beneficial effect on the trajectory of brain aging. Funding: The German Research Foundation (DFG), German Research Foundation - project number 209933838 - SFB 1052; B11, Israel Ministry of Health grant 87472511 (to I Shai); Israel Ministry of Science and Technology grant 3-13604 (to I Shai); and the California Walnuts Commission 09933838 SFB 105 (to I Shai).

Many proposals to resolve the current Israeli constitutional crisis have been recently advanced. Yet, most of them are arguably unlikely to bring about a compromise. This is so not because their content cannot be accepted by the parties involved, but because they do not address the substantive concerns of the parties. Israel’s constitutional crisis results from the fact that the parties to the conflict shape their proposals concerning the decision-making process in a way that is conducive to their short-term substantive interests. Any proposed solution must therefore separate substantive questions from procedural and institutional ones.

Abstract Longitudinal data are vital in order to understand intra individual gait changes with the progression of multiple sclerosis (MS). Therefore, the primary aim of this study was to explore the relationship between changes in disability with changes in major spatio-temporal parameters of gait in people with MS (PwMS). PwMS (n = 83) completed two gait assessments performed at separate time points (M1, M2). For each individual, the absolute difference between the Expanded Disability Status Scale (EDSS) score, key spatio-temporal parameters of gait, Falls Efficacy Scale International (FES-I), and the 12-item Multiple Sclerosis Walking Scale (MSWS-12), were calculated. The mean time difference between M1 and M2 was 2.5 (SD = 1.7) years. At M2, PwMS presented with shorter strides, a wider base of support, increased perceived mobility difficulties and fear of falling compared with M1. According to the odds ratio (OR) analysis, the odds of experiencing an increase in the EDSS score was significantly higher once the MSWS-12 score increased at M2 compared with M1 (OR = 7.930, p = 0.004). This observation was highlighted specifically in people with mild-moderate MS (OR = 12.427, p

Abstract Background Previous studies have linked the Mediterranean diet (MED) with improved cardiometabolic health, showing preliminary evidence for a mediating role of the gut microbiome. We recently suggested the Green-Mediterranean (Green-MED) diet as an improved version of the healthy MED diet, with increased consumption of plant-based foods and reduced meat intake. Here, we investigated the effects of MED interventions on the gut microbiota and cardiometabolic markers, and the interplay between the two, during the initial weight loss phase of the DIRECT-PLUS trial. Methods In the DIRECT-PLUS study, 294 participants with abdominal obesity/dyslipidemia were prospectively randomized to one of three intervention groups: healthy dietary guidelines (standard science-based nutritional counseling), MED, and Green-MED. Both isocaloric MED and Green-MED groups were supplemented with 28g/day walnuts. The Green-MED group was further provided with daily polyphenol-rich green tea and Mankai aquatic plant (new plant introduced to a western population). Gut microbiota was profiled by 16S rRNA for all stool samples and shotgun sequencing for a select subset of samples. Results Both MED diets induced substantial changes in the community structure of the gut microbiome, with the Green-MED diet leading to more prominent compositional changes, largely driven by the low abundant, “non-core,” microorganisms. The Green-MED diet was associated with specific microbial changes, including enrichments in the genus Prevotella and enzymatic functions involved in branched-chain amino acid degradation, and reductions in the genus Bifidobacterium and enzymatic functions responsible for branched-chain amino acid biosynthesis. The MED and Green-MED diets were also associated with stepwise beneficial changes in body weight and cardiometabolic biomarkers, concomitantly with the increased plant intake and reduced meat intake. Furthermore, while the level of adherence to the Green-MED diet and its specific green dietary components was associated with the magnitude of changes in microbiome composition, changes in gut microbial features appeared to mediate the association between adherence to the Green-MED and body weight and cardiometabolic risk reduction. Conclusions Our findings support a mediating role of the gut microbiome in the beneficial effects of the Green-MED diet enriched with Mankai and green tea on cardiometabolic risk factors. Trial registration The study was registered on ClinicalTrial.gov ( NCT03020186 ) on January 13, 2017.

Peripheral nerve damage that results in lost segments requires surgery, but currently available hollow scaffolds have limitations that could be overcome by adding internal guidance support. A novel solution is to use filaments of absorbable metals to supply physical support and guidance for nerve regeneration that then safely disappear from the body. Previously, we showed that thin filaments of magnesium metal (Mg) would support nerve regeneration. Here, we tested another absorbable metal, zinc (Zn), using a proprietary zinc alloy with 2% iron (Zn-2%Fe) that was designed to overcome the limitations of both Mg and pure Zn metal. Non-critical-sized gaps in adult rat sciatic nerves were repaired with silicone conduits plus single filaments of Zn-2%Fe, Mg, or no metal, with autografts as controls. After seventeen weeks, all groups showed equal recovery of function and axonal density at the distal end of the conduit. The Zn alloy group showed some improvements in early rat health and recovery of function. The alloy had a greater local accumulation of degradation products and inflammatory cells than Mg; however, both metals had an equally thin capsule (no difference in tissue irritation) and no toxicity or inflammation in neighboring nerve tissues. Therefore, Zn-2%Fe, like Mg, is biocompatible and has great potential for use in nervous tissue regeneration and repair.

Trade-off between transient response and grid-side current quality is a well-known issue of single-phase mains-connected power converters. A dual-loop control structure (usually based on PI or type-II controllers) is typically employed in such systems to regulate the DC link voltage to a constant reference (in order to maintain power balance) while forcing the grid-side current to have a specific shape (in order to comply with power quality requirements). Introducing notch term/s (tuned to certain multiple/s of the mains base frequency) into one of the loops allows either for the improvement of the dynamic performance without worsening the total harmonic distortion of grid-side current or for the enhancement of the current quality without impairing the dynamic response. Since the maximum tolerable value of total harmonic distortion is typically imposed by a certain power quality standard, it is desirable to enhance the transient response of the power converter system as much as possible while keeping the total harmonic distortion at the maximum allowed value. However, universal off-grid operating power conversion systems must support both 50 Hz and 60 Hz mains; consequently, tuning the notch term/s to 50 Hz multiple/s would not be sufficient for a 60 Hz mains operation and vice-versa. Consequently, this work examines the possibility of introducing a dual-notch term into the control loop in order to cover both above-mentioned base frequencies. It is demonstrated that under typical base frequency uncertainty values, the performances of dual-notch terms are nearly decoupled so that the term tuned to a 50 Hz frequency (and optionally to its multiples) has nearly no influence at a 60 Hz mains operation and vice-versa. Consequently, the methodology allows for the improvement of the dynamics of universal grid-connected power converters without total harmonic distortion (THD) deterioration. A stability analysis of the proposed control structure is carried out and quantitative design guidelines, allowing for the attainment of an optimized dynamic response for a given maximum tolerable total harmonic distortion, minimum allowed phase margin and a certain base frequency uncertainty, are established. It is shown that a DC link voltage loop bandwidth of 52 Hz may be attained while keeping the grid-side current THD below 5%. Simulations and experimental results support well the proposed design methodology.

Abstract Background Inversion Symmetry is a generalization of the second Chargaff rule, stating that the count of a string of k nucleotides on a single chromosomal strand equals the count of its inverse (reverse-complement) k-mer. It holds for many species, both eukaryotes and prokaryotes, for ranges of k which may vary from 7 to 10 as chromosomal lengths vary from 2Mbp to 200 Mbp. Building on this formalism we introduce the concept of k-mer distances between chromosomes. We formulate two k-mer distance measures, D1 and D2, which depend on k. D1 takes into account all k-mers (for a single k) appearing on single strands of the two compared chromosomes, whereas D2 takes into account both strands of each chromosome. Both measures reflect dissimilarities in global chromosomal structures. Results After defining the various distance measures and summarizing their properties, we also define proximities that rely on the existence of synteny blocks between chromosomes of different bacterial strains. Comparing pairs of strains of bacteria, we find negative correlations between synteny proximities and k-mer distances, thus establishing the meaning of the latter as measures of evolutionary distances among bacterial strains. The synteny measures we use are appropriate for closely related bacterial strains, where considerable sections of chromosomes demonstrate high direct or reversed equality. These measures are not appropriate for comparing different bacteria or eukaryotes. K-mer structural distances can be defined for all species. Because of the arbitrariness of strand choices, we employ only the D2 measure when comparing chromosomes of different species. The results for comparisons of various eukaryotes display interesting behavior which is partially consistent with conventional understanding of evolutionary genomics. In particular, we define ratios of minimal k-mer distances (KDR) between unmasked and masked chromosomes of two species, which correlate with both short and long evolutionary scales. Conclusions k-mer distances reflect dissimilarities among global chromosomal structures. They carry information which aggregates all mutations. As such they can complement traditional evolution studies , which mainly concentrate on coding regions.

Herein, centrosymmetric aluminum plasmonic structures composed of triangular cavities are studied and their long‐range coupling by cathodoluminescence nanoscopy are visualized. Four different plasmonic structures containing the same subunit are studied. The plasmonic modes of the individual triangular subunits are localized at the triangle sides rather than at the vertices, in agreement with other studies. Yet, upon strong interaction between the cavities, a redistribution of the electromagnetic field is observed such that it delocalizes around the cavities in the form of a contour, providing a mode enhancement and a pronounced nonlinear response as observed by second harmonic generation. Comparison between plasmonic structures made of either silver or aluminum reveals that the metal dielectric function plays an important role in the interaction between the cavities. This work provides a rationale for designing plasmonic structures with enhanced nonlinear activity.

BackgroundMultiple sclerosis (MS) is a common nontraumatic, neurological, disabling disease that often presents with upper limb dysfunction. Exercise training has resulted in improvement for patients; however, there can be a lack of compliance due to access because of location and lack of MS experts. Virtual reality (VR) is a promising technology that can offer exercise therapy/rehabilitation at a distance. This type of remote training can be motivational and effective for patients with MS and can improve range of motion and muscle strength for those with upper limb dysfunction. ObjectiveThe aim of this study is to evaluate the safety and feasibility of the XRHealth software and the Oculus Rift Station for patients with MS with upper limb motor dysfunction. MethodsA single-center, prospective, feasibility study was conducted with patients with MS who had upper limb motor dysfunction. Patients participated in a single 45-minute digital environment session with VR and completed a questionnaire about the quality of the training and fatigability. The clinician also completed a questionnaire to evaluate the suitability and safety of the training. ResultsOverall, 30 patients were enrolled between the ages of 20 and 81 years. Patients reported that the training sessions within the digital environment were helpful, challenging, fun, and simple to understand, and that they would be willing to repeat the sessions again. The physical therapist that oversaw the patients reported that the training was suitable for 87% (n=26) of the patients. Anticipated adverse events were fatigue, temporary dizziness, and temporary nausea. The operator complications included that the cable of the head-mounted display interrupted the training (n=2, 7%) and fatigue that caused cessation of the VR training session (n=2, 7%). No serious adverse events were reported. ConclusionsThese preliminary results demonstrated that the use of the XRHealth software and Oculus Rift Station platform is feasible, safe, and engaging for patients, and has the potential to improve the functionality of the upper limbs in patients with MS. This study provides support for future studies of implementing a series of training sessions with virtual reality in a home-based environment.

Purpose: Open-air motor vehicles present unique trauma risks to the eyes and face. We describe two patients who suffered a crash while riding an all-terrain vehicle (ATV), leading to globe dislocation with optic nerve avulsion in order to raise awareness about the risks associated with ATV accidents. Observations: In both cases, the injury was caused by high-speed trauma to the orbit involving a tree branch. One patient sustained a life threatening arrythmia requiring a short stay in the intensive care unit, and both patients required emergent surgical management and eventual socket reconstruction. Conclusions and Importance: These cases highlight the need for greater advocacy on behalf of rider safety. The authors encourage ophthalmologists to counsel patients who use ATVs to wear helmets, seatbelts, and protective eyewear to prevent these types of injuries in the future.

Background: The motoric cognitive risk (MCR) syndrome, defined as the coexistence of slow gait and subjective cognitive complaints, has as yet not been researched in people with multiple sclerosis (pwMS). Objective: To examine the prevalence of the MCR syndrome in pwMS and its association with disability, disease duration, perceived fatigue, and fear of falling. Methods: The study comprised 618 pwMS [43.7 (SD = 12.6) years, 61.7% females]. Gait speed was measured by the GAITRite™ electronic walkway (CIR Systems, Inc. Haverton, PA, USA). Cognitive status was defined according to the global cognitive score computed by the NeuroTrax™ cognitive battery (NeuroTrax Corporation, Medina, NY, USA). The sample was divided into four main groups: ‘normal’, ‘cognitively impaired’, ‘gait impaired’ or ‘MCR’. Perceived fatigue was assessed by the Modified Fatigue Impact Scale; fear of falling by the Falls Efficacy Scale International. Results: Sixty-three (10.2%) patients were diagnosed with MCR. The percentage of subjects categorized as MCR was 26.0% in severely disabled pwMS compared with 10.9%, 6.0%, and 4.6% in moderately, mildly and very mildly disabled pwMS, respectively. Subjects in the MCR group presented with elevated fatigue compared with patients classified as normal [49.7 (SD = 23.3) vs 26.5 (SD = 19.2), p

Statistical characteristics of the wind speed in the Samaria region of Israel have been analyzed by processing 11 years of wind data provided by the Israeli Meteorological Service, recorded at a 10 m height above the ground. The cumulative mean wind speed at a measurement height was shown to be 4.53 m/s with a standard deviation of 2.32 m/s. The prevailing wind direction was shown to be characterized by a cumulative mean azimuth of 226° with a standard deviation of 79.76°. The results were extrapolated to a 70 m height in order to estimate wind characteristics at the hub height of a medium-scale wind turbine. Moreover, Weibull distribution parameters were calculated annually, monthly, and seasonally, demonstrating a good match with histogram-based statistical representations. The shape parameter of the Weibull distribution was shown to reside within a narrow range of 1.93 to 2.15, allowing us to assume a Rayleigh distribution, thus simplifying wind turbine energy yield calculations. The novelty of the current paper is related to gathering wind statistics for a certain area (Samaria), and we are not aware of any published statistics regarding wind velocity and direction in this area. These data may be interesting for potential regional wind energy development in which the obtained Weibull distribution could be used in calculations for the expected power generation of particular turbines with a known power dependence on velocity. We have given an example of these calculations for three different types of turbines and obtained their yield in terms of electric power and economic value. We also point out that the fact that realistic wind velocity statistics can be described well by an analytic formula (Weibull distribution) is not trivial, and in fact, the fit may have been poor.

Abstract Programmable nano-bio interfaces driven by tuneable vertically configured nanostructures have recently emerged as a powerful tool for cellular manipulations and interrogations. Such interfaces have strong potential for ground-breaking advances, particularly in cellular nanobiotechnology and mechanobiology. However, the opaque nature of many nanostructured surfaces makes non-destructive, live-cell characterization of cellular behavior on vertically aligned nanostructures challenging to observe. Here, a new nanofabrication route is proposed that enables harvesting of vertically aligned silicon (Si) nanowires and their subsequent transfer onto an optically transparent substrate, with high efficiency and without artefacts. We demonstrate the potential of this route for efficient live-cell phase contrast imaging and subsequent characterization of cells growing on vertically aligned Si nanowires. This approach provides the first opportunity to understand dynamic cellular responses to a cell-nanowire interface, and thus has the potential to inform the design of future nanoscale cellular manipulation technologies.

Summary: Volatile short-chain fatty acids such as butyric and acetic acid have been supplemented in poultry rations as a feed ingredient and nutritive supplement. A novel Clostridium fermentation solubles broth (MiruTyton), containing short-chain fatty acids, minerals, and amino acids, was supplemented in a standard corn/soybean meal–based ration at a rate of 750, 1,500, 3,000, and 6,000 mg/kg to achieve approximately 277, 554, 1,108, and 2,216 mg/kg of ammonium butyrate in the diet. After 6 wk, supplementation at all levels did not cause significant changes in the blood parameters or any live performance metric of mixed-sex Cobb-500 broilers (N = 1,920). In addition, administering 6,000 mg/kg of MiruTyton caused no significant lesions in any of the tissue examined except for an increase (P