Hyperlipidemia Induced Pathological Changes with no Effect in Biomechanical Properties in the Achilles Tendon of Young Swine.

Hyperlipidemia is linked to atherosclerosis and various diseases. Its strong association with Achilles tendinopathies and xanthomas affects tendon properties through lipid deposition in tendon tissue. We examined the impact of hyperlipidemia on the biomechanical properties of the swine Achilles tendons. Swines were fed a high-cholesterol-high-fat diet to induce hyperlipidemia, and their Achilles tendons were collected and examined for biomechanical properties. The ultimate tensile strength, modulus of elasticity and viscoelastic properties did not exhibit significant differences between hyperlipidemic and control swines. H&E and pentachrome staining revealed extracellular matrix (ECM) disorganization and cellular infiltration in the hyperlipidemic swines, highlighting a marked difference between the control and hyperlipidemic groups. These results suggest hyperlipidemia in young swines alters the tendon composition and may contribute to weak biomechanical properties with time.

Rotator Cuff Tendon Repair after Injury in Hyperlipidemic Swine Decreases Biomechanical Properties.

Rotator cuff injury is the leading cause of shoulder pain. Hyperlipidemia is responsible in depositing lipids in tendons and reduce the healing upon injuries or tears. In this study, we created rotator cuff injury and repair models in swine and studied the changes in biomechanical properties of infraspinatus tendons in hyperlipidemic swine. The infraspinatus tendons from control group, hyperlipidemic injury and repair group of animals were collected and tested ex-vivo. The ultimate tensile strength (UTS) and modulus of elasticity increased in the tendons from the contralateral side on both the injury and repair models and were higher than the injury side. The presence of large number of fibrous tissues in the surgical site of repair and increased water content was observed in addition to the fatty infiltration which would have contributed to the decreased mechanical properties of the injured tendons following repair. Meanwhile the tendons of the contralateral side in both the injury and repair model showed adaptation to chronic load as observed in the modulus and viscoelastic properties. This is a pilot study that warrants detailed investigation in a larger sample size with longer duration following tendon injury and repair to gain better understanding on the effect of hyperlipidemia in the healing of rotator cuff tendon injury.

Dual crosslinked pullulan-gelatin cryogel scaffold for chondrocyte-mediated cartilage repair: synthesis, characterization andin vitroevaluation.

Cryogels, a subset of hydrogels, have recently drawn attention for cartilage tissue engineering due to its inherent microporous architecture and good mechanical properties. In this study a dual crosslinked pullulan-gelatin cryogel (PDAG) scaffold was synthesized by crosslinking gelatin with oxidized pullulan by Schiff's base reaction followed by cryogelation. Chondrocytes seeded within the PDAG scaffolds and cultured for 21 din vitrodemonstrated enhanced cell proliferation, enhanced production of cartilage-specific extracellular matrix and up-regulated sulfated glycosaminoglycan without altering the articular chondrocyte phenotype. Quantitative reverse transcription-polymerase chain reaction-based gene expression studies, immunofluorescence, and histological studies demonstrated that the PDAG scaffold significantly enhanced the expression of chondrogenic marker genes such as type II collagen, aggrecan, and SOX9. Taken together, these results demonstrated that PDAG scaffold prepared by sequential Schiff's base reaction and cryogelation would be a promising cell-responsive scaffold for cartilage tissue engineering applications.

Compression after Impact Behaviour and Failure Analysis of Nanosilica-Toughened Thin Epoxy/GFRP Composite Laminates.

Nanosilica particles were utilized as secondary reinforcement to enhance the strength of the epoxy resin matrix. Thin glass fibre reinforced polymer (GFRP) composite laminates of 3 ± 0.25 mm were developed with E-Glass mats of 610 GSM and LY556 epoxy resin. Nanosilica fillers were mixed with epoxy resin in the order of 0.25, 0.5, 0.75 and 1 wt% through mechanical stirring followed by an ultrasonication method. Thereafter, the damage was induced on toughened laminates through low-velocity drop weight impact tests and the induced damage was assessed through an image analysis tool. The residual compression strength of the impacted laminates was assessed through compression after impact (CAI) experiments. Laminates with nanosilica as secondary reinforcement exhibited enhanced compression strength, stiffness, and damage suppression. Results of Fourier-transform infrared spectroscopy revealed that physical toughening mechanisms enhanced the strength of the nanoparticle-reinforced composite. Failure analysis of the damaged area through scanning electron microscopy (SEM) evidenced the presence of key toughening mechanisms like damage containment through micro-cracks, enhanced fiber-matrix bonding, and load transfer.

Chitosan-agarose scaffolds supports chondrogenesis of Human Wharton's Jelly mesenchymal stem cells.

Tissue engineering strategies for cartilage aim to restore the complex biomechanical and biochemical properties of the native cartilage. To mimic the in vivo microenvironment, we developed a novel scaffold based on chitosan-agarose (CHAG scaffold) resembling the properties of native cartilage extracellular matrix (ECM) that aids in vitro cartilage formation. The CHAG scaffolds had pore size ranging from 75 to 300 µm and the degradation of 18% over 6 months in PBS. L929 cells and Human Wharton's Jelly-Mesenchymal Stem Cells (HWJ-MSCs) attached well and grew in the CHAG scaffolds. HWJ-MSCs seeded on CHAG scaffolds and cultured in chondrogenic medium were able to differentiate into chondrogenic lineage. Simultaneous supplementation of growth factors (BMP-2, TGF-ß3) significantly enhanced chondrogenesis and neo ECM synthesis. CHAG scaffolds seeded with HWJ-MSCs cultured in chondrogenic media supplemented with both BMP-2 and TGF-ß3 produced 12.71 ± 1.0 µg GAG/µg DNA compared to the one which received no or either of the growth factors. Our findings suggest that CHAG scaffolds could be used as a biomaterial scaffold for cell mediated repair approaches based on HWJ-MSCs for articular cartilage. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1845-1855, 2017.

Safety assessment of Withania somnifera extract standardized for Withaferin A: Acute and sub-acute toxicity study.

BACKGROUND: The use of Withania somnifera is increasing due to a number of its chemical constituents found useful for health. OBJECTIVE: The present study was carried out to investigate the potential adverse effects (if any) of a standardized Withania somnifera extract (WSE) in rats following acute and sub chronic administration. MATERIALS AND METHODS: The toxicity study was performed in Wistar rats by oral administration. An acute toxicity study was done at the dose of 2000 mg/kg. In the sub-acute study, Wistar rats (10/sex/group) were administered via gavage 0 (control), 500, 1000, 2000 mg/kg body weight/day of WSE for 28 days. Among two additional satellite groups, one group did not receive any drug while the second group received 2000 mg/kg/day for 28 days. At the end of study, the animals sacrificed and their body weight, hematology, serum chemistry, and histopathology evaluation was done. RESULTS: In acute toxicity studies, oral LD50 of WSE in Wistar rats was greater than 2000 mg/kg body weight. Compared to the control group in sub-acute toxicity study, administration of extract did not show any toxicologically significant treatment related changes in clinical observations, ophthalmic examination, body weight gain, feed consumption, clinical pathology evaluation, and organ weight. Hematological and serum chemistry parameters were within the normal limits. Terminal necropsy did not reveal any treatment related gross or histopathological findings. CONCLUSION: Based on this study, the no-observed-adverse-effect-level of WSE is 2000 mg/kg body weight, the highest level tested.

Symptoms of depression and rates of neurocognitive impairment in HIV positive patients in Beijing, China.

BACKGROUND: In China an estimated 780,000 people are living with HIV (PLWH). In high-income countries PLWH are at increased risk of depression, with subsequent adverse consequences for quality of life, and HIV-related morbidity and mortality. There are few data from low-and middle-income countries. The aims of this country-specific investigation of the Asia Pacific NeuroAIDS Consortium (APNAC) study were to establish the point prevalence, severity and HIV-related and non-HIV related correlates of depressive symptoms in PLWH, in Beijing, China. METHOD: PLWH attending an outpatient clinic at Ditan Hospital, Beijing were recruited consecutively. Data sources were: study-specific questions about demographic characteristics, and health behaviours, the Centre for Epidemiological Studies Depression Scale (CES-D), the World Health Organisation Self-Reporting Questionnaire (SRQ-20) translated into Mandarin and administered as structured individual interviews, and a screen battery of four standard neuropsychological tests. RESULTS: In total 50/51 (98%) eligible patients agreed to participate. Overall 28% scored CES-D≥16 or SRQ20≥10 and 18% in these clinical ranges on both measures; 69% were classified as being neuropsychologically impaired (scoring below 1 SD of the control value on at least two tests). Higher depressive symptom scores were associated with lower education, alcohol overuse and diminished motor ability (all p<0.05), but not neuropsychological impairment CONCLUSION: Clinically significant depressive symptoms among this cohort of PLWH in Beijing occurred at 5 times the rate reported among a general Chinese urban population. No participants had been assessed for depression prior to the study and none were treated, indicating that consideration of psychological morbidity and its consequences for health behaviours should be incorporated into routine HIV care in China.

A prospective study evaluating clinical outcomes and costs of three NNRTI-based HAART regimens in Kerala, India.

OBJECTIVE: This prospective, observational, study evaluates the clinical outcomes, drug utilization patterns, and adherence to treatment of patients on highly active anti retroviral therapy (HAART) at a government institution in Kerala, India. METHODS: Patients who met criteria for treatment of HIV/AIDS were enrolled into the study, given free NNRTI-based combination therapy, and were followed for a period of 6 months. Data regarding demographics, clinical outcome, laboratory results, drug utilization, adherence and adverse effects were collected. Analysis was conducted utilizing descriptive statistics, anova, Fisher-exact, andt-test. RESULTS: One hundred and forty-two patients with HIV-1 were enrolled in the study into three treatment groups. The mean age was 37.88 years, 64% of the patients were male, and 92% were married. Group 1 was given zidovudine, lamivudine, and nevirapine [n = 52 (37%)], group 2 was given lamivudine, stavudine, and nevirapine [n = 51 (36%)], and group 3 was given lamivudine, stavudine, and efavirenz [n = 39 (27%)]. The increase in CD4 was 107.46 (SD: 106.25). Mean medication adherence for the 104 patients who completed the study, was 90.7%; for group 1: 92.06%, group 2: 93.37%1, and group 3: 85.71% (P > 0.05). Forty (38%) patients have at least one adverse event to HARRT, with headache being the most common side effect (11.5%). Mortality rate was 3.5% during the course of the study. CONCLUSION: Provision of free NNRTI-based combination therapy to patients in Kerala, India, resulted in greater than 90% adherence leading to better clinical outcomes in terms of increasing CD4 counts and low mortality, for patients consistently attending a treatment clinic.

Neurologic disorders are prevalent in HIV-positive outpatients in the Asia-Pacific region.

BACKGROUND: A total of 8.3 million HIV-positive people live in the Asia-Pacific region. The burden of HIV-associated neurocognitive impairment and symptomatic sensory neuropathy in this region is unknown. METHODS: Between July 2005 and March 2006, we undertook a cross-sectional study at 10 sentinel sites within eight Asia-Pacific countries to determine the prevalence of moderate to severe HIV-related neurocognitive impairment and symptomatic sensory neuropathy. We clinically assessed and administered sensitive neuropsychological and peripheral neuropathy screening tools to 658 patients infected with HIV. Univariate and logistic regression analyses were applied to the data. RESULTS: The results showed that 76 patients (11.7%) (95% CI 9.3-14.2) were significantly neurocognitively impaired, 235 patients (36.4%) (95% CI 32.7-40.2) were depressed, and 126 patients (19.7%) (95% CI 16.6-22.8) had either definite or probable symptomatic sensory neuropathy; 63% of this last group had exposure to stavudine, didanosine, or zalcitabine. Several potential confounders including depression (OR 1.49, 95% CI 0.88-2.51, p = 0.11) and prior CNS AIDS illness (OR 1.28, 95% CI 0.50-2.89, p = 0.54) were not significantly associated with neurocognitive impairment. CONCLUSIONS: A total of 12% of patients had moderate to severe HIV-related neurocognitive impairment, 20% of patients had symptomatic sensory neuropathy, and 36% of patients had evidence of depression. This study provides a broad regional estimate of the burden of HIV-related neurologic disease and depression in the Asia-Pacific region.

The impact of pharmacist-managed oral anticoagulation therapy in older veterans.

BACKGROUND: Older adults frequently have conditions requiring oral anticoagulation. Although clearly benefiting from oral anticoagulation, they are at increased risk for bleeding complications. Regular monitoring to optimize anticoagulation and to reduce the chance of major bleeding complications is required. The impact of oral anticoagulation monitoring by pharmacists in patients older than 75 years of age has not been described well. OBJECTIVE: To compare warfarin therapy prescribed and monitored by physicians to a pharmacist-monitored anticoagulation service in a cohort of older veterans. METHODS: Retrospective chart review utilizing the Houston VA Medical Center's pharmacy database. Among all outpatients aged 75 years or older filling warfarin prescriptions between 1 March 2003 to 1 March 2005, and who were either monitored in a pharmacist's clinic or not, 103 patients per group were randomly selected. Information on demographics, indication for and length of warfarin therapy, INR values, and thromboembolic and bleeding events were abstracted. Differences were analysed using chi-squared test, Fisher's Exact test, and unpaired Student t-test. RESULTS: A total of 1521 patients (440 in the pharmacist-monitored group, 1081 in the traditionally monitored group) met our inclusion criteria. One hundred and three patients per group were randomly selected for chart review. Although no significant difference in percentage of therapeutic INR values (48.1% pharmacist group, 46.4% conventional group) or in the incidence of major bleeding events was found, thromboembolic events occurred significantly less frequently in the pharmacist-monitored group (2 events vs. 12 events, P = 0.01). Minor bleeding events were more frequent in the pharmacist-monitored group (50 vs. 17, P < 0.01). However, time to follow-up after a sub- or supra-therapeutic INR was significantly shorter in the pharmacist monitored group (22 days vs. 68 days, and 14 days vs. 32 days, respectively). CONCLUSION: Pharmacist-monitored anticoagulation was associated with reduced thromboembolic events, an increase in minor bleeding events, and no difference in major bleeding events. Overall such monitoring by pharmacists should be recommended for older adults.

A retrospective study to determine the impact of medical- and lifestyle-based contraindications to a prescribed HAART regimen on clinical outcomes and adherence.

OBJECTIVE: To determine whether patients who are prescribed a highly active antiretroviral therapy regimen, that minimizes medical and lifestyle contraindications, will be better able to adhere to their drug regimens and will have better clinical outcomes, than patients who do not have such a regimen. METHODS: A retrospective chart review of patients' prescription renewals and changes in viral load and CD4(+) count and a comparison of these changes with patients' self-identified contraindications. Contraindications were identified by a questionnaire with 35 questions relating to medical history/concurrently prescribed medication and 16 questions on lifestyle. Main outcome measures are adherence assessed by prescription renewals, change in plasma HIV-1 RNA viral loads, and change in CD4(+) T-lymphocyte counts. Logistic and linear regression and student t-test were used to identify associations between outcome measurements and number of contraindications. RESULTS: A total of 203 patients (72% male, 74% African-American, 7% Hispanic) completed the questionnaire. Seventy-four per cent of the patients had at least one medical/drug contraindication and 78% had at least one lifestyle contraindication. Increases in CD4 counts were reduced by an average of 13 cells/mm(3) (P = 0.033) for each medical/drug contraindication and viral load decreases was significant even with one medical contraindication vs. none (P = 0.042). Patients with fewer lifestyle contraindications were more likely to have at least a 1 log drop in viral load (P = 0.036). For each increase in the number of contraindications, there was a corresponding 2% decrease in the rate of adherence (P = 0.048). CONCLUSIONS: The results suggest that using a patient administered questionnaire it is possible to identify contraindications in prescribed regimens that impact on adherence and on treatment effects on viral load and CD4 counts.

Antiretroviral use and other risks for HIV-associated neuropathies in an international cohort.

OBJECTIVE: To explore the association between specific nucleoside reverse transcriptase inhibitors and sensory neuropathies (SNs) and define the modifying roles of hepatitis C (HCV), vitamin B12 deficiency, and impaired glucose tolerance. METHODS: The authors conducted a prospective cohort study of 147 HIV-infected adults at two sites chosen to emphasize demographic differences. Standardized assessments included detailed antiretroviral histories, neurologic examinations, skin biopsies for epidermal nerve quantitation, and quantitative sensory testing. RESULTS: There were significant differences between subjects at Johns Hopkins University (JHU) and Monash University (MU) in gender, race, HIV transmission route, and HCV seroprevalence. Symptomatic SN was present in 49% at JHU and 55% at MU (chi2 = 4.02, p = 0.134) and was significantly more common in those at least age 40 than younger patients (odds ratio [OR] = 2.87, 95% CI = 1.27, 6.49). After adjusting for site, age, and CD4 cell count, exposure to didanosine (ddI) or stavudine (d4T) was associated with an significantly increased likelihood of symptomatic SN (ddI: OR = 3.21, 95% CI: 1.56, 6.60; d4T: OR = 7.66, 95% CI: 2.89, 20.33). Plasma HIV RNA, lactate, and HCV were not associated with SN. Quantitative vibratory testing identified neuropathy with a positive predictive value of 76% and epidermal nerve fiber densities 59%. CONCLUSIONS: Exposure to stavudine and didanosine was significantly associated with a heightened risk for symptomatic sensory neuropathy. Reduced vibration thresholds and epidermal nerve fiber densities had the highest diagnostic efficiency of the laboratory indicators of neuropathy examined, but were relatively insensitive in isolation.

Position-dependent protein mutant profile based on mean force field calculation.

The application of the mean force field in protein mutant stability prediction is explored. Based on protein main chain characteristics, including polar fraction, accessibility and dihedral angles, the mean force field was constructed to evaluate the compatibility between an amino acid residue and its environment, from which a position-dependent protein mutant profile was constructed. At each position along a protein sequence, the native residue was replaced by the other 19 types of amino acid residues. The matches were evaluated by energies from mean force field calculation, from which a mutant profile along the protein sequence was derived. General characteristics of such a profile were analyzed. Mutant stabilities for two sets of mutants in two proteins were found to be reasonable compared with experimental data, which indicates that the present method can act as a guide in protein engineering and as an effective scoring matrix in protein sequence-structure alignment studies.

Documentation of the first steps of pediatric pharmaceutical care in a county hospital.

Pediatric pharmaceutical care is still a new concept in the pharmacy profession. In our county institution with 35% of the beds reserved for pediatric patients, there existed no formal process for providing specialized pediatric pharmacy services. In an effort to rectify this situation, a study was conducted to determine the benefits of providing pharmaceutical services by having a clinical pharmacist round with physicians on a daily basis for 3 hours. All services provided were documented for 6 months and direct cost-savings were calculated. Five hundred four different interventions and services were provided, with over $7000 in savings. Because of these findings, the pharmacy and hospital administration agreed to provide a staff pharmacist to round in pediatrics on a regular basis. This approach is considered to be more cost effective than using a clinical pharmacist for daily rounds.