Effects of individually optimized rocker midsoles and self-adjusting insoles on dynamic stability in persons with diabetes mellitus and neuropathy.

BACKGROUND: Persons with diabetic peripheral neuropathy (DPN) may face challenges such as balance issues due to reduced somatosensory feedback and an increased risk of developing diabetic foot ulcers (DFUs) due to increased plantar pressure. Pressure reducing footwear is thought to further impair balance. We introduced 3D-printed rocker midsoles and self-adjusting insoles that are able to reduce elevated plantar pressure values and aimed to prevent balance deterioration. However, their effect on the balance during walking (dynamic stability) is not analyzed yet. RESEARCH QUESTION: Is dynamic stability of persons with DPN impaired compared to healthy individuals and what is the effect of the 3D-printed rocker midsoles and self-adjusting insoles on the dynamic stability in this population? METHODS: Dynamic stability, specifically the margins of stability (MOS) in the anterior-posterior (AP) and medio-lateral (ML) direction, was measured in ten healthy and nineteen persons with DPN. Independent-samples t-test was applied to analyze the difference in the MOS between groups. One-way repeated measures analyses of variance (ANOVA) was conducted to test the difference between the therapeutic footwear combinations within the DPN group. RESULTS: There is no significant difference between the healthy and DPN group in MOS-AP. MOS-ML is significantly larger in DPN compared to the healthy participants. Using the self-adjusting insole shows a significantly lower (negative) MOS-AP compared to when using a rocker shoe within the DPN group. SIGNIFICANCE: This study provides valuable information on whether DPN and our therapeutic footwear have a negative effect on the dynamic stability. DPN does not have a negative effect on dynamic stability in the AP direction. For the ML direction, DPN seems to cause larger MOS-ML by likely using a compensation strategy (e.g., wider steps) while our experimental footwear does not further impair the MOS-ML.

Effects of individually optimized rocker midsoles and self-adjusting insoles on plantar pressure in persons with diabetes mellitus and loss of protective sensation.

INTRODUCTION: Rocker shoes and insoles reduce peak pressure (PP) in persons with diabetes (DM) and loss of protective sensation (LOPS). However, they are handmade, leading to inconsistent effectiveness. If foot structure changes over time, high PP-locations also change. To address this, individualized algorithm based 3D-printed rockers and self-adjusting pressure-reducing insoles are applied. METHODS: PP across seven foot regions was analyzed in 21 persons with DM and LOPS. Regions with PP < 200 kPa were considered not at risk (RnoR); regions with PP ≥ 200 kPa at risk (RaR). The aim was to offload RaR, while remaining PP < 200 kPa in RnoR. RESULTS: Individualized rockers and self-adjusting insoles combined successfully reduce PP < 200 kPa (on average 24 % - 48 %) in all feet with toes, central and lateral forefoot identified as RaR. Same intervention reduces PP in 68 % of the feet with medial forefoot identified as RaR. With the heel as RaR, no intervention reduces PP successfully in all feet. CONCLUSIONS: Individualized 3D-printed rockers combined with self-adjusting insoles reduce PP (< 200 kPa) in toes, central and lateral forefoot, but not in heels. Alternative insoles with medial arch support, heel cup and compliant midsole materials might enhance success rate across entire foot.

Red blood cell derived extracellular vesicles during the process of autologous blood doping.

The purpose of this pilot study was to investigate the effects of the transfusion of one erythrocyte concentrate on the number of circulating red blood cell extracellular vesicles (RBC-EVs) and their clearance time. Six, healthy volunteers donated their blood and were transfused with their RBC concentrate after 35-36 days of storage. One K2 EDTA and one serum sample were collected before donation, at four timepoints after donation and at another six timepoints after transfusion. RBC-EVs were analyzed on a Cytek Aurora flow cytometer. A highly significant increase (p < 0.001) of RBC-EVs from an average of 60.1 ± 19.8 (103 /µL) at baseline to 179.3 ± 84.7 (103 /µL) in the first 1-3 h after transfusion could be observed. Individual differences in the response to transfusion became apparent with one volunteer showing no increase and another an increased concentration at one timepoint after donation due to an influenza infection. We concluded that in an individualized passport approach, increased RBC-EVs might be considered as additional evidence when interpreting suspicious Athletes Biological Passport (ABPs) but for this additional research related to sample collection and transport processes as well as method development and harmonization would be necessary.

Prevalence of Toxoplasma gondii infection in diabetic patients in Makkah AL Mukarramah, Saudi Arabia.

Toxoplasmosis is a parasitic and zoonotic disease caused by Toxoplasma gondii. The disease has worldwide distribution and all people maybe under the risk of getting infected by the parasite. The overall aim of this research was to detect the prevalence rate of antiToxoplasma gondii IgM and IgG among diabetic patients in Makkah, Saudi Arabia. Blood samples were collected from diabetic patients. Toxo IgM and IgG combo rapid test cassette were used to screen the samples, and the results were confirmed by using Enzyme-Linked Immunosorbent Assay (ELISA) to detect anti-IgM and anti- IgG antibodies on the plasma of 90 diabetic patients who attended the mobile clinic or AL Noor hospital in Makkah area. The subject was asked to complete a structured questionnaire. The questionnaire data and serological results were analyzed by using SPSS 20. Chi-square was used to compare different variables. Out of 90 samples, 39 (43.3%) were positive to anti-Toxoplasma gondii IgG wherein 33 (36.6%) of them were male and 6 (6.7%) were female. The age ranged between 13-85 years with the mean of 49.9 years. The study found that there were statistical differences between the age groups with higher prevalence in the 50-65 years age group. Detection of IgM against T. gondii gave negative results. The results of the study indicate that latent T. gondii in diabetic patient are relatively high especially among the 50-65 age group. There were significant associated between direct contact with a cat and infection by T. gondii (p<0.05).

Testicular sperm aspiration (TESA) for infertile couples with severe or complete asthenozoospermia.

The aim of the study was to evaluate reproductive outcomes in a cohort of infertile couples with severe and complete asthenozoospermia undergoing TESA (testicular sperm aspiration) with ICSI. We conducted a retrospective study of 28 couples with complete or severe asthenozoospermia who underwent TESA between January 2010 and December 2015. We compared TESA-ICSI outcomes of these couples to ejaculate ICSI outcomes of 40 couples with severe asthenozoospermia treated during the same time period at our institution. Couples with female factor infertility and/or female aged ≥39 were excluded. Sperm retrieval rates and ICSI outcomes [(MII oocytes, fertilization rate, good embryo rate (transferred and frozen), couples with embryo transfer (per cycle started), clinical pregnancy (per embryo transfer)] were recorded. Patients were grouped based on whether they had ejaculated (Ej-group) or testicular (TESA-group) spermatozoa used. Testicular sperm patients were further classified based on whether they had complete asthenozoospermia (0% total motility) (Tc-group) or severe asthenozoospermia (≤1% progressive motility) (Ts-group). Mean (±SD) male and female ages were 36 ± 6 and 32 ± 4, respectively. Sperm recovery by testicular sperm aspiration (TESA) was successful in 100% (28/28) of the men. The overall clinical pregnancy rate (CPR) per cycle started was 34% (23/68) with a mean of 1.1 ± 0.4 embryos transferred per transfer. Fertilization rates were significantly lower in TESA-group compared to Ej-group (52% vs. 67%, respectively; p = 0.001), while male age was significantly higher in TESA-group compared to Ej-group (34 ± 6 vs. 37 ± 6, respectively; p = 0.03). Moreover, female age was significantly higher in Tc-group compared to Ts-group (30 ± 4 vs. 33 ± 3, respectively; p = 0.0285). However, there were no significant difference in clinical pregnancy rate per embryo transfer in the Tc-group, Ts-group, and Ej-group (50% vs. 45% vs. 57%, respectively; p = 0.8219). The data suggest that testicular sperm-ICSI is no better than ejaculated sperm-ICSI in couples with severe or complete asthenozoospermia. Randomized, controlled trials comparing ejaculated vs. testicular spermatozoa are needed to assess the true benefit of TESA-ICSI in these couples.

Glucose- and Triglyceride-lowering Dietary Penta-O-galloyl-α-D-Glucose Reduces Expression of PPARγ and C/EBPα, Induces p21-Mediated G1 Phase Cell Cycle Arrest, and Inhibits Adipogenesis in 3T3-L1 Preadipocytes.

Plant polyphenols, such as hydrolysable tannins, are present in the human diet and known to exhibit anti-diabetic and anti-obesity activity. We previously reported that the representative hydrolysable tannin compound α-penta-galloyl-glucose (α-PGG) is a small molecule insulin mimetic that, like insulin, binds to insulin receptor (IR) and activates the IR-Akt-GLUT4 signaling pathway to trigger glucose transport and reduce blood glucose levels in db/db and ob/ob diabetic mice. However, its effects on adipogenesis and lipid metabolism were not known. In this study, high fat diet (HFD)-induced diabetic and obese mice were treated with α-PGG to determine its effects on blood glucose and triglycerides. 3T3-L1 preadipocytes were used as a cell model for identifying the anti-adipogenic activity of α-PGG at molecular and cellular levels as a first step in elucidating the mechanism of action of the compound. In vivo, oral administration of α-PGG significantly reduced levels of blood glucose, triglyceride, and insulin in HFD-induced diabetic/obese mice (P<0.05). In vitro, α-PGG inhibited the differentiation of 3T3-L1 preadipocytes into mature adipocytes. α-PGG suppressed the expression of positive adipogenic factors PPARγ C/EBPα and mTOR and augmented the negative adipogenic factor Pref-1. Furthermore, α-PGG induced upregulation of p21 and G1 phase cell cycle arrest. In contrast, adipogenic signaling pathways mediated by insulin, the cAMP response element binding protein (CREB) and glucocorticoid receptor (GR), were not inhibited. RNAi knockdown of p21 led to a 4-fold increase in triglyceride level in 3T3-L1 preadipocytes treated with MDI and α-PGG compared to regular preadipocytes. These results indicate, for the first time, that α-PGG is blood triglyceride- and glucose-lowering in HFD-induced obese and diabetic mice. It selectively inhibited some but not all major adipogenic pathways as well as the mTOR-p21-mediated cell cycle regulatory pathway. It is very likely that these apparently diverse but coordinated activities together inhibited adipogenesis. These results expand our knowledge on how PGG works in adipocytes and further confirm that α-PGG functions as an orally-deliverable natural insulin mimetic with adipogenetic modulatory functions.

Biochemical modulation of cell energy by 2-deoxyglucose and malonate in 7,12-dimethylbenz(a)anthracene-induced carcinogenesis in rats.

The goal of this study was to explore the impact of 2-deoxglucose or malonate individually or in combination on the level of cell energy (adenosine-5'-triphosphate) and oxidative stress in 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary proliferation in rats. A total of 60 adult female Sprague Dawley rats were randomly divided into five groups (12 rats each): group I serves as the control group. Rats in groups (II-V) were administrated intragastrically a single dose of 50 mg/kg body weight (bw) of DMBA. A day after DMBA administration, rats in group III were injected intraperitoneally (ip) with 100 mg 2-deoxyglucose (2-DG)/kg bw daily. Rats in group IV were injected ip with 10 mg sodium malonate/kg bw daily. Rats in group V were injected ip with 100 mg 2-DG/kg bw and 10 mg sodium malonate/kg bw (treatment for 90 days). The results obtained showed that DMBA induced oxidative stress by decreasing the activities of glutathione reductase (GRase) and superoxide dismutase (SOD), glutathione peroxidase (GPx) and elevating the levels of malondialdehyde (MDA) and nitric oxide (NO) in mammary tissues when compared with control. The combined treatment protected against the previous deleterious changes by a significant elevation in the activities of GRase and SOD, GPx and lowering the levels of MDA and NO more potentially when compared with individual treatment. Apoptosis, as indicated by a significant release of cytochrome c from mitochondria into the cytosol, observed in DMBA-injected rats was positively significantly correlated with the elevation of the level of NO. These data explained the possible additive effect of 2-DG and malonate by depleting the cell energy by their protective effects against the earlier stages of carcinogenesis.

Novel quinuclidinone derivatives induce apoptosis in lung cancer via sphingomyelinase pathways.

We previously reported novel quinuclidinone analogs which induced apoptosis in lung and breast cancer cells. In this study, we designed and synthesized novel quinuclidinone analogs that showed cytotoxicity in lung cancer cells. The effects of these analogs were studied in H1299 human large cell lung carcinoma cells that are null for p53 and normal lung epithelial cell lines (NL-20). The effects of the analogs were investigated by MTT assay, ELISA based apoptotic assay, TUNEL assay, sphingomylinase activity, flow cytometry and western blot analysis. Our data indicated that derivatives 4 and 6 decreased cell proliferation and induced apoptosis in H1299 cells more than NL-20 cells. Derivatives 4 and 6 reduced percent of cells in G2/M phase in H1299 cells more than NL-20 cells and these results were confirmed by increased expression levels of cyclin E. Furthermore, derivatives 4 and 6 increased sphingomyelinase activity, caspase-8, and caspase-9 and JNK-1 expression level in H1299. Additionally, derivatives 4 and 6 induced Procaspase-3, PARP-1 cleavage, and increased caspase-3 activity. All these results confirm that our quinuclidinone derivatives provoke cytotoxicity in lung cancer cells through the interplay of key apoptosis molecules in different compartments of the cell beginning with an increase in sphingomyelinase activity.

Effects of a water-soluble curcumin protein conjugate vs. pure curcumin in a diabetic model of erectile dysfunction.

INTRODUCTION: Curcumin is involved in erectile signaling via elevation of cyclic guanosine monophosphate (cGMP). AIM: Assessment of the effects of water-soluble curcumin in erectile dysfunction (ED). METHODS: One hundred twenty male white albino rats were divided into: 1st and 2nd control groups with or without administration of Zinc protoporphyrin (ZnPP), 3rd and 4th diabetic groups with or without ZnPP, 5th diabetic group on single oral dose of pure curcumin, 6th diabetic group on pure curcumin administered daily for 12 weeks, 7th and 8th diabetic groups on single dose of water-soluble curcumin administered with or without ZnPP, 9th and 10th diabetic groups on water-soluble curcumin administered daily for 12 weeks with or without ZnPP. All curcumin dosage schedules were administered after induction of diabetes. MAIN OUTCOME MEASURES: Quantitative gene expression of endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), inducible NOS (iNOS), heme oxygenase-1 (HO-1), nuclear transcription factor-erythroid2 (Nrf2), NF-Кß, and p38. Cavernous tissue levels of HO and NOS enzyme activities, cGMP and intracavernosal pressure (ICP). RESULTS: Twelve weeks after induction of diabetes, ED was confirmed by the significant decrease in ICP. There was a significant decrease in cGMP, NOS, HO enzymes, a significant decrease in eNOS, nNOS, HO-1 genes and a significant elevation of NF-Кß, p38, iNOS genes. Administration of pure curcumin or its water-soluble conjugate led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in eNOS, nNOS, HO-1, and Nrf2 genes, and a significant decrease in NF-Кß, p38, and iNOS genes. Water-soluble curcumin showed significant superiority and more prolonged duration of action. Repeated doses regimens were superior to single dose regimen. Administration of ZnPP significantly reduced HO enzyme, cGMP, ICP/ mean arterial pressure (MAP), HO-1 genes in diabetic groups. CONCLUSION: Water-soluble curcumin could enhance erectile function with more effectiveness and with more prolonged duration of action.

Design, synthesis and evaluation of novel benzimidazoles, benzothiazoles and benzofurans incorporating pyrazole moiety as antiangiogenic agents.

Novel benzimidazoles, benzothiazoles and benzofurans incorporating pyrazole moiety have been synthesized and screened for their antiangogenic activities, by testing their ability to inhibit human umbilical vein endothelial cell (HUVEC) proliferation, cord formation and migration in response to chemoattractant. 3 compounds 19, 23 and 26 showed antiangiogenic activities at non-cytotoxic concentrations. Compound 19 was the most active with chemotaxis activity data nearly comparable to that of the positive control, TNP-470. Compound 42 showed a significant cytotoxic effect on the tested cancer cell lines and less antiangiogenesis activity compared to compounds 19, 23 and 26. All the tested compounds, in contrary to TNP-470, interfered with the migratory function of HUVECs in response to vascular endothelial growth factor rather than the endothelial cells proliferation or cord formation. Moreover, a docked pose of compounds 19 and 26 was obtained bound to kinase insert domain receptor using Molecular Operating Environment module.

Measurement of radon diffusion length in thin membranes.

Building regulations in Israel require the insulating of buildings against radon (222)Rn penetration from soil. In radon-prone areas membranes stretched between the soil and the building foundation are used, together with sealing other possible penetration routes. Designing the radon mitigation procedure requires checking that all sealing materials are practically, radon tight, having a thickness of at least three times the radon diffusion length. In this work, a very simple technique to evaluate the radon diffusion length in thin membranes, using a radon source of known activity and an activated charcoal canister as radon detector is presented. The theoretical formalism and measurement results for polyethylene membranes of different densities obtained in a recent comparison exercise are presented.

[Hepatitis B prevalence and risk factors in Morocco]. / Prévalence de l'infection par le virus de l'hépatite B et l'évaluation des facteurs de risque au Maroc.

AIM: The aim of this study was to determine the prevalence of hepatitis B and the risk factors in Morocco. STUDY DESIGN: A total number of 16,634 individuals were screened for HBsAg using the Murex HBsAg Version 3 assay and were interviewed using a structured standard questionnaire to collect information about risk factor. RESULTS: Two hundred seventy-six subjects were positive for HBsAg, the prevalence of HBV infection was 1.66%. Using a structured standard questionnaire we reported that sexual behaviours (43.84%) are among the main risk factors for HBV transmission. CONCLUSION: This study indicates that the prevalence of HBsAg in Morocco is currently estimated at 1.66% in the active population. The risk factors for HBV infection identified here indicate that prevention is the most cost-effective method for successfully controlling HBV infection, so vaccination remains the best way to control this infection and its related complications.

Managing femoral head osteonecrosis in patients with sickle cell disease.

With an increasing number of people immigrating between different countries, sickle cell disease (SCD) is spreading all over the world. Due to improved health care, the life span of SCD patients has increased and many of them live to adulthood and middle-age. Osteonecrosis of the femoral head is one of the most common musculo-skeletal problems in SCD patients. Once osteonecrosis starts in the femoral head, it can progress from early to late stages in just a few years. Managing osteonecrosis of the femoral head in young-adults is a challenging problem and, in many situations, it requires major surgical procedures. In the early stages of the disease it is advisable to treat it by femoral head preserving procedures. In advanced stages, hip replacement arthroplasty (HPA) is indicated. In SCD patients, the incidence of operative complications and failure rates are higher than that for osteonecrosis due to other causes. Understanding the problems of SCD patients; appropriate diagnosis, prognosis, implications of the procedure performed and taking the necessary precautions, can reduce the complications and delay the failure of surgical procedures.

Differential effect of selected methylxanthine derivatives on radiosensitization of lung carcinoma cells.

AIM: Using caffeine as a reference derivative, this study was performed to investigate how other methylxanthine derivatives, theophylline, 3-isobutyl-methylxanthine and 1,3-dipropyl-7-methylxanthine, sensitize cells to radiation by modifying cell cycle checkpoints and inducing the apoptotic response. The effect of the methylxanthine derivatives was studied in response to gamma and ultraviolet radiation in a human large cell lung carcinoma cell line, null for p53, a normal lung epithelial cell line and the large cell lung carcinoma cell line stably transfected with p53. METHODS: Effects of theophylline, 3-isobutyl-methylxanthine and 1,3-dipropyl 7-methylxanthine on cell-radiosensitization in comparison to caffeine tested by clonogenic survival assay, MTT assay, ELISA based apoptotic assay, flow cytometry, caspase-3 activity, TUNEL assay, and western blot analysis. RESULTS: All the derivatives, except 3-isobutyl-methylxanthine, increased tumor cell sensitization to radiation by inducing apoptosis in the p53-null lung cancer cell line. The pattern of cell cycle progression revealed that these derivatives increased the number of cells in G1 phase by abrogating the G2/M checkpoint, directing the cells to apoptose through a p53-independent mechanism. In contrast, 3-isobutyl-methylxanthine was more potent than the other derivatives in radiosensitization of normal lung epithelial cells and the lung carcinoma cells stably transfected with wild-type p53. IBMX increased p53 protein level more than caffeine in lung carcinoma cells stably transfected with wild-type p53. CONCLUSION: Our results suggest that 3-isobutyl-methylxanthine might function through a p53-dependent mechanism.

n-p short-range correlations from (p,2p+n) measurements.

We studied the 12C(p,2p+n) reaction at beam momenta of 5.9, 8.0, and 9.0 GeV/c. For quasielastic (p,2p) events p(f), the momentum of the knocked-out proton before the reaction, was compared (event by event) with p(n), the coincident neutron momentum. For |p(n)|>k(F)=0.220 GeV/c (the Fermi momentum) a strong back-to-back directional correlation between p(f) and p(n) was observed, indicative of short-range n-p correlations. From p(n) and p(f) we constructed the distributions of c.m. and relative motion in the longitudinal direction for correlated pairs. We also determined that 49+/-13% of events with |p(f)|>k(F) had directionally correlated neutrons with |p(n)|>k(F).

Total hip replacement in sickle cell disease.

We report on 35 total hip replacement arthroplasties in 28 patients with avascular necrosis of the femoral head secondary to sickle cell disease (SCD). There were 15 men and 13 women with a mean age of 27.5 years. In all patients Harris hip scores improved from a mean of 36 pre-operative to 86 post-operative. However, at a mean follow-up of 9.5 (5-15) years six hips failed due to symptomatic aseptic loosening and one due to late deep infection. Our results support the decision to offer the procedure for patients with arthritic hips secondary to SCD. It is important that patients and surgeons should be aware of the wide varieties of complications.

Energy dependence of nuclear transparency in C (p,2p) scattering.

The transparency of carbon for (p,2p) quasielastic events was measured at beam momenta ranging from 5.9 to 14.5 GeV/c at 90 degrees c.m. The four-momentum transfer squared (Q2) ranged from 4.7 to 12.7 (GeV/c)(2). We present the observed beam momentum dependence of the ratio of the carbon to hydrogen cross sections. We also apply a model for the nuclear momentum distribution of carbon to obtain the nuclear transparency. We find a sharp rise in transparency as the beam momentum is increased to 9 GeV/c and a reduction to approximately the Glauber level at higher energies.

Competition between the replication initiator DnaA and the sequestration factor SeqA for binding to the hemimethylated chromosomal origin of E. coli in vitro.

BACKGROUND: Following replication initiation, the replication origin (oriC) in Escherichia coli enters a hemimethylated state at Dam methylation sites which are recognized by the SeqA protein. SeqA binds preferentially to hemimethylated GATC sequences of DNA in vitro. SeqA is essential for the synchronous initiation of chromosome replication from oriC copies in vivo. RESULTS: We show that: (i) purified SeqA binds AT-rich and 13-mers regions and two DnaA boxes, R1 and M, of hemimethylated oriC. (ii) SeqA inhibits the in vitro replication of a hemimethylated oriC plasmid more efficiently than the fully methylated, (iii) SeqA inhibits competitive binding of DnaA protein to the regions of the hemimethylated oriC plasmid, explaining the mechanism of its inhibitory effect. The inhibition of DnaA binding by SeqA also occurs efficiently on a small hemimethylated oriC fragment containing both R1 and M DnaA boxes, but not the 13-mer region. CONCLUSIONS: SeqA binds strongly the long region from the AT-rich region to the M DnaA box of the hemimethylated oriC DNA and releases DnaA molecules from the long region.

Centralization of ulna for infected nonunion of radius with extensive bone loss. A modified Hey-Groves procedure.

We describe a case of infected nonunion of the radius with extensive bone loss in an 11-year-old boy treated by centralization of the ulna. The technique used differs from the original Hey Groves procedure in that it preserves the distal end of the ulna with its important triangular fibrocartilage complex, thereby retaining stability and contour of the wrist joint. Our patient obtained a functionally and cosmetically satisfactory, stable forearm and wrist. We present the technique as a useful armament in the management of extensive bony defect of the radius arising from trauma or infection.