α/Sulfono-γ-AA peptide hybrids agonist of GLP-1R with prolonged action both in vitro and in vivo

Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t 1/2 > 14 days) compared to t 1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.

Drug-abusing offenders with co-morbid mental disorders: gender differences in problem severity, treatment participation, and recidivism / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>This study examined the gender differences in drug-related problems and predictors of recidivism among a sample of 1444 offenders with co-morbid drug abuse and mental disorders participating in California's Proposition 36 Program.</p><p><b>METHODS</b>Background characteristics and problem severity in multiple key life areas were assessed at intake by using Addiction Severity Index, and drug treatment participation, mental health diagnoses and arrests were based on official records.</p><p><b>RESULTS</b>Women demonstrated greater problem severity than men in family relationships, health, psychological health, and sexual and physical abuse history. Men on the other hand had greater criminal history, high rates of attention disorder, and psychotic disorder. More men than women were rearrested during the year after treatment admission. Logistic regression analyses showed that for the combined sample, male, young age, cocaine use (relative to methamphetamine), drug abuse severity, methadone treatment, arrest history and fewer prior treatment history were associated with higher recidivism at 12-month follow-up; lower education, cocaine use, and arrest history were related to women's recidivism, while young age, outpatient treatment, and arrest history were predictors of men's recidivism.</p><p><b>CONCLUSION</b>Although the specific type of mental disorder did not seem to be predictive of recidivism, the high rates of mental health disorder and arrest of this population is problematic. Intervention strategies taking into consideration gender-specific problems and needs can improve outcomes for both.</p>

Intraocular lens power calculation after myopic and hyperopic laser vision correction using optical coherence tomography

To use optical coherence tomography [OCT] to measure corneal power and calculate intraocular lens [IOL] power in cataract surgeries after myopic and hyperopic laser vision correction [LVC]. Patients with previous LVC were enrolled in this prospective study at two centers [Doheny Eye Institute, Los Angeles, CA, USA and Cullen Eye Institute, Houston, TX, USA]. Corneal power was measured with a Fourier-domain OCT system. The intravisit repeatability of OCT corneal power measurement was evaluated by the pooled standard deviation of repeat scans. Axial length, anterior chamber depth, and automated keratometry were measured with the IOLMaster. An OCT-based IOL formula was developed. The mean absolute error [MAE] of refractive prediction for OCT-based IOL formula was calculated. The results were compared with the MAE for Haigis-L formula. A total of 31 eyes of 24 subjects who had uncomplicated cataract surgery with monofocal IOL implantation were enrolled in the two sites. Twenty-two eyes of 16 subjects had previous myopic LVC ranged from -12.46 D to -0.88 D. Nine eyes of 8 subjects had previous hyperopic LVC ranged from 0.66 D to 5.52 D. The intravisit repeatability of OCT corneal power measurement was 0.24 D. For the myopic LVC group, the OCT formula had a MAE of 0.57 D compared to an MAE of 0.73 D for the Haigis-L formula [p = 0.19]. For the hyperopic LVC group, the MAE for OCT and Haigis-L formula was 0.26 D and 0.54 D, respectively [p > 0.05]. Corneal power can be precisely measured with OCT. The predictive accuracy of OCT-based IOL power calculation is equal to current standards for post-LVC eyes

Effects of age on ocular anterior segment dimensions measured by optical coherence tomography / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Older subjects tend to have smaller ocular anterior segment. The present study aimed to measure anterior segment dimensions with optical coherence tomography (OCT) and quantitatively assess the effect of age and other factors.</p><p><b>METHODS</b>Anterior segment OCT images were obtained in normal subjects residing in the greater Los Angeles area. Four line scans were acquired at the 90°, 45°, 0° and 135° meridians of each eye. Computer calipers acquired anterior segment dimensions of corneal diameter, anterior chamber width, corneal vault and anterior chamber depth on OCT images. Measurements from 4 meridians were averaged. Axial length and corneal power were measured by partial coherence interferometry. Univariate and multivariate analyses were performed to assess correlations.</p><p><b>RESULTS</b>Sixty-six eyes of 33 normal subjects (aged 22 - 65 years, 19 Asians, 14 Caucasians) were enrolled. For every 1 year of age, corneal diameter was 0.033 mm narrower (P < 0.01), anterior chamber width was 0.031 mm narrower (P < 0.01), corneal vault was 0.016 mm lower (P < 0.01), and anterior chamber depth was 0.025 mm lower (P < 0.01). Asian eyes had smaller corneal diameter (P = 0.035) and anterior chamber width (P = 0.015) compared with those of Caucasian eyes. Body height showed positive correlation with corneal diameter (0.039 mm per centimeter of height, P < 0.01) and corneal vault (0.024 mm per centimetre of height, P < 0.01). Gender did not have an independent effect on anterior segment dimensions.</p><p><b>CONCLUSIONS</b>Anterior segment dimensions were smaller in older subjects. Age-related changes may affect the tolerability of long-term implants such as phakic intraocular lens.</p>

Risk factors for lower limb swelling after primary total knee arthroplasty / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Total knee arthroplasty (TKA) is a successful surgical technique for patients with advanced knee osteoarthritis; however, some peri-operative complications can not be predicted or avoided completely. This study aimed to investigate the factors affecting limb swelling after primary total knee arthroplasty, to guide and improve patient rehabilitation.</p><p><b>METHODS</b>Using a hospital database, we retroactively analyzed the mean changes in limb circumferences of 286 consecutive patients who underwent primary unilateral total knee arthroplasty between October 2007 and August 2009. The lower limb circumference change was calculated and analyzed statistically. The influence of age, gender, body mass index, the presence of deep vein thrombosis, methods of anti-coagulation, operation time, hidden blood loss, and type of prosthesis on post-operative lower limb swelling was studied.</p><p><b>RESULTS</b>Swelling was most pronounced from the third to the fifth post-operative day and usually occurred in both lower limbs. Swelling was significantly more pronounced in the operated limb than in the non-operated limb. The swelling above the knee was also significantly greater than that below the knee. The change in limb circumference at 10 cm above the knee was significantly different between the patients with body mass index ≤ 25 kg/m(2) and those with body mass index > 25 kg/m(2). However, the change in limb circumference at 10 cm below the knee was not significantly different between the two groups. There was no statistically significant difference in limb swelling between different age groups (P > 0.05). Similarly, gender, methods of anti-coagulation, the presence of deep vein thrombosis, the type of prosthesis, and operation time did not significantly affect post-operative limb swelling. Multivariate linear regression showed that the factors affecting post-operative limb swelling were body mass index and hidden blood loss.</p><p><b>CONCLUSIONS</b>Lower limb swelling after total knee arthroplasty is related to early post-operative hidden blood loss. The patient's hemoglobin level should be monitored. The degree of limb swelling is correlated with the patient's body mass index and the amount of hidden blood loss. Early intramuscular deep vein thrombosis formation has little effect on limb swelling.</p>

Stereotactic Aspiration and Drainage on a Patient with Large Lobar Hemorrhage and Brain Herniation A Case Report / 国际脑血管病杂志

A 43-year-old man was diagnosed as massive left occipital lobe hemorrhage with the hematoma expanded into the entire ventricular system. On admission, he was in deep coma with clinical signs of brain herniation and a Glasgow Coma Scale (GCS) score of 4. Vascular malformations were highly suspected since he was young with no history of hypertension. Considering the life-threatening situation, open craniotomy and hematoma evacuation was proposed as the first therapeutic option, but this was refused by his family members for non-medical reasons. In order to save his life, stereotactic aspiration was suggested again and was accepted. UK at an aggressive dosage of 50 000 IU was administered during and after the surgical procedure for 5 days. One month later, this patient gained an excellent recovery with a Glasgow Outcome Scale (GOS) score of 5.