Handgrip Strength and Its Associated Factors among Community-dwelling Elderly in Sri Lanka: A Cross-sectional Study

Purpose

Low muscle strength is central to geriatric physical disabilities and mortality. The purpose of the present study was to examine handgrip strength (HGS) and its associated factors among community-dwelling older people in Sri Lanka.

Spermatozoa protein alterations in infertile men with bilateral varicocele

Among infertile men, a diagnosis of unilateral varicocele is made in 90% of varicocele cases and bilateral in the remaining varicocele cases. However, there are reports of under-diagnosis of bilateral varicocele among infertile men and that its prevalence is greater than 10%. In this prospective study, we aimed to examine the differentially expressed proteins (DEP) extracted from spermatozoa cells of patients with bilateral varicocele and fertile donors. Subjects consisted of 17 men diagnosed with bilateral varicocele and 10 proven fertile men as healthy controls. Using the LTQ-orbitrap elite hybrid mass spectrometry system, proteomic analysis was done on pooled samples from 3 patients with bilateral varicocele and 5 fertile men. From these samples, 73 DEP were identified of which 58 proteins were differentially expressed, with 7 proteins unique to the bilateral varicocele group and 8 proteins to the fertile control group. Majority of the DEPs were observed to be associated with metabolic processes, stress responses, oxidoreductase activity, enzyme regulation, and immune system processes. Seven DEP were involved in sperm function such as capacitation, motility, and sperm-zona binding. Proteins TEKT3 and TCP11 were validated by Western blot analysis and may serve as potential biomarkers for bilateral varicocele. In this study, we have demonstrated for the first time the presence of DEP and identified proteins with distinct reproductive functions which are altered in infertile men with bilateral varicocele. Functional proteomic profiling provides insight into the mechanistic implications of bilateral varicocele-associated male infertility.     

Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility

To study the major differences in the distribution of spermatozoa proteins in infertile men with varicocele by comparative proteomics and validation of their level of expression. The study-specific estimates for each varicocele outcome were combined to identify the proteins involved in varicocele-associated infertility in men irrespective of stage and laterality of their clinical varicocele. Expression levels of 5 key proteins (PKAR1A, AK7, CCT6B, HSPA2, and ODF2) involved in stress response and sperm function including molecular chaperones were validated by Western blotting. Ninety-nine proteins were differentially expressed in the varicocele group. Over 87% of the DEP involved in major energy metabolism and key sperm functions were underexpressed in the varicocele group. Key protein functions affected in the varicocele group were spermatogenesis, sperm motility, and mitochondrial dysfunction, which were further validated by Western blotting, corroborating the proteomics analysis. Varicocele is essentially a state of energy deprivation, hypoxia, and hyperthermia due to impaired blood supply, which is corroborated by down-regulation of lipid metabolism, mitochondrial electron transport chain, and Krebs cycle enzymes. To corroborate the proteomic analysis, expression of the 5 identified proteins of interest was validated by Western blotting. This study contributes toward establishing a biomarker “fingerprint” to assess sperm quality on the basis of molecular parameters.     

Phosphorylated ganciclovir derivatives: design,synthesis and in vitro and in vivo immunomodulatory activity

Synthesis of a series of novel phosphorylated ganciclovir derivatives with bioactive amines/aminoacid esters as substituents was accomplished. These compounds were structurally characterized by IR, NMR (¹H, ¹³C, ³¹P), mass spectra and CHN analysis. The compounds (5a–m) have been evaluated for its in vitro and in vivo immunomodulatory activities. The amino acid ester-substituted ganciclovir derivatives, especially the 5g and 5i, increased the intracellular killing activity of the stimulated neutrophils. The in vivo experiment results show that the administration of compounds 5g and 5i (8 mg/kg body weight) to diet-induced immune impaired obese rats ameliorated the significant increase in immune cell counts (lymphocytes, neutrophils and monocytes). In addition, TNF-α, IL-6 and IL-1 secretions were considerably restored to normal by the compounds 5g and 5i with regulation in the release of C-reactive protein suggesting their potentiating effect on immune system dysfunction. These in vitro and in vivo results suggest that the phosphorylated ganciclovir derivatives 5g and 5i are strong immunomodulators.     

Canagliflozin,a sodium glucose co-transporter 2 inhibitor,reduces post-meal glucose excursion in patients with type 2 diabetes by a non-renal mechanism: results of a randomized trial

Objective

Canagliflozin is a sodium glucose co-transporter 2 inhibitor approved for treating patients with type 2 diabetes. This study evaluated renal and non-renal effects of canagliflozin on postprandial plasma glucose (PG) excursion in patients with type 2 diabetes inadequately controlled with metformin.

Materials/Methods

Patients (N = 37) were randomized to a four-period crossover study with 3-day inpatient stays in each period and 2-week wash-outs between periods. Patients received Treatments (A) placebo/placebo, (B) canagliflozin 300 mg/placebo, (C) canagliflozin 300 mg/canagliflozin 300 mg, or (D) canagliflozin 300 mg/canagliflozin 150 mg on Day 2/Day 3 in one of four treatment sequences (similar urinary glucose excretion [UGE] expected for Treatments B–D). A mixed-meal tolerance test (MMTT) was given 20 minutes post-dose on Day 3 of each period.

Results

A single dose of canagliflozin 300 mg reduced both fasting and postprandial PG compared with placebo, with generally similar effects on fasting PG and UGE observed for Treatments B–D. An additional dose of canagliflozin 300 mg (Treatment C), but not 150 mg (Treatment D), prior to the MMTT on Day 3 provided greater postprandial PG reduction versus placebo (difference in incremental glucose AUC_0–2h, − 7.5% for B vs A; − 18.5% for C vs A; − 12.0% [P = 0.012] for C vs B), leading to modestly greater reductions in total glucose AUC_0–2h with Treatment C versus Treatment B or D. Canagliflozin was generally well tolerated.

Conclusions

These findings suggest that a non-renal mechanism (ie, beyond UGE) contributes to glucose lowering for canagliflozin 300 mg, but not 150 mg.     

The risk of contralateral lymphatic metastases for cancers of the larynx and pharynx.

PURPOSE: This study was undertaken to determine the risk of cervical metastases to the contralateral side in patients treated for carcinoma of the larynx and pharynx. PATIENTS AND METHOD: Retrospective evaluation of 846 patients treated between 1962 and 1981 with carcinoma of the supraglottis, transglottis, and pyriform sinus were reviewed. Lesions were classified as either transglottic with fixed vocal cord (TG-F), transglottic with mobile vocal cords (TG-M), central supraglottic (SG-C), marginal supraglottic (SG-M), glossoepiglottic cancers of the suprahyoid epiglottic, vallecula, and tongue base (SG-GE), and cancers of the pyriform sinus (PS). RESULTS: Contralateral lymph node metastases were identified at presentation or later developed in SG-GE 26%, SG-M 14%, PS 13%, SG-C 7%, TG 4%. Contralateral metastases were significantly higher in patients with ipsilateral metastasis. The risk of contralateral metastasis was unrelated to the primary tumor size. CONCLUSIONS: All but 79 patients received variable doses of irradiation to the contralateral neck. Therefore, the risk of metastatic disease is probably higher than reported. Parotid-sparing radiation technique is suggested for centrally located cancers of the supraglottis and transglottis when ipsilateral nodes are not involved because the risk of contralateral neck involvement is sufficiently low that opposite neck irradiation may be safely avoided.     

Prophylactic positive end-expiratory pressure and reduction of postoperative blood loss in open-heart surgery

BACKGROUND: Various strategies have been introduced to minimize transfusion requirements in cardiac surgery. One strategy is the use of positive end-expiratory pressure (PEEP) postoperatively. Currently, PEEP is used in many centers to control increased mediastinal chest-tube drainage. The purpose of this study was to determine whether the prophylactic application of a PEEP of 10 cm H2O compared with a PEEP of 5 cm H2O in the immediate postoperative period reduces mediastinal chest-tube output without causing clinically significant hemodynamic compromise. METHODS: We prospectively studied 84 elective coronary artery bypass grafted patients and randomized treatment groups to a PEEP of 5 or 10 cm H2O. Forty-four patients were assigned a PEEP of 5 cm H2O and 40 patients received a PEEP of 10 cm H2O. RESULTS: Preoperative, intraoperative, and postoperative demographics were similar between groups. There was no statistically significant difference between the 5 cm H2O PEEP group and the 10 cm H2O PEEP group with regard to chest-tube output at 6 hours, at 24 hours, or in total output. There was no statistical difference in hemoglobin levels immediately postoperatively, at 8 hours, or at 36 hours. CONCLUSIONS: This study demonstrates that the use of postoperative PEEP levels of 10 cm H2O, although safe, does not reduce chest-tube output or transfusion requirements.     

Pharmacokinetics and pharmacodynamics of a transdermal contraceptive patch and an oral contraceptive

This open-label, randomized, 2-way crossover study characterized the pharmacokinetics and pharmacodynamics of a transdermal contraceptive patch and a norgestimate-containing oral contraceptive. Healthy women (n = 34) applied a patch once weekly for 3 consecutive weeks during each of 2 cycles and received an oral contraceptive for 21 consecutive days during each of 2 cycles. Plasma concentrations of norelgestromin and ethinyl estradiol peaked and waned after daily oral contraceptive administration, whereas they rose and reached steady-state levels after first patch application. Norelgestromin exposure was similar; ethinyl estradiol exposure was higher for the patch than oral contraceptive. Hepatic estrogenic activity, assessed by hepatic globulin synthesis, was similar for corticosteroid-binding globulin and corticosteroid-binding globulin-binding capacity and higher for sex hormone-binding globulin for the patch versus oral contraceptive. The clinical significance of the differences in pharmacokinetic and pharmacodynamic profiles between the patch and oral contraceptive is not fully known. No serious adverse events or discontinuations due to adverse events were recorded.