Swd2/Cps35 determines H3K4 tri-methylation via interactions with Set1 and Rad6.

BACKGROUND: Histone H3K4 tri-methylation (H3K4me3) catalyzed by Set1/COMPASS, is a prominent epigenetic mark found in promoter-proximal regions of actively transcribed genes. H3K4me3 relies on prior monoubiquitination at the histone H2B (H2Bub) by Rad6 and Bre1. Swd2/Cps35, a Set1/COMPASS component, has been proposed as a key player in facilitating H2Bub-dependent H3K4me3. However, a more comprehensive investigation regarding the relationship among Rad6, Swd2, and Set1 is required to further understand the mechanisms and functions of the H3K4 methylation. RESULTS: We investigated the genome-wide occupancy patterns of Rad6, Swd2, and Set1 under various genetic conditions, aiming to clarify the roles of Set1 and Rad6 for occupancy of Swd2. Swd2 peaks appear on both the 5' region and 3' region of genes, which are overlapped with its tightly bound two complexes, Set1 and cleavage and polyadenylation factor (CPF), respectively. In the absence of Rad6/H2Bub, Set1 predominantly localized to the 5' region of genes, while Swd2 lost all the chromatin binding. However, in the absence of Set1, Swd2 occupancy near the 5' region was impaired and rather increased in the 3' region. CONCLUSIONS: This study highlights that the catalytic activity of Rad6 is essential for all the ways of Swd2's binding to the transcribed genes and Set1 redistributes the Swd2 to the 5' region for accomplishments of H3K4me3 in the genome-wide level.

Surface Crystal and Degradability of Shape Memory Scaffold Essentialize Osteochondral Regeneration.

The minimally invasive deployment of scaffolds is a key safety factor for the regeneration of cartilage and bone defects. Osteogenesis relies primarily on cell-matrix interactions, whereas chondrogenesis relies on cell-cell aggregation. Bone matrix expansion requires osteoconductive scaffold degradation. However, chondrogenic cell aggregation is promoted on the repellent scaffold surface, and minimal scaffold degradation supports the avascular nature of cartilage regeneration. Here, a material satisfying these requirements for osteochondral regeneration is developed by integrating osteoconductive hydroxyapatite (HAp) with a chondroconductive shape memory polymer (SMP). The shape memory function-derived fixity and recovery of the scaffold enabled minimally invasive deployment and expansion to fill irregular defects. The crystalline phases on the SMP surface inhibited cell aggregation by suppressing water penetration and subsequent protein adsorption. However, HAp conjugation SMP (H-SMP) enhanced surface roughness and consequent cell-matrix interactions by limiting cell aggregation using crystal peaks. After mouse subcutaneous implantation, hydrolytic H-SMP accelerated scaffold degradation compared to that by the minimal degradation observed for SMP alone for two months. H-SMP and SMP are found to promote osteogenesis and chondrogenesis, respectively, in vitro and in vivo, including the regeneration of rat osteochondral defects using the binary scaffold form, suggesting that this material is promising for osteochondral regeneration.

Multiplex Detection of Foodborne Pathogens using 3D Nanostructure Swab and Deep Learning-Based Classification of Raman Spectra.

Proactive management of foodborne illness requires routine surveillance of foodborne pathogens, which requires developing simple, rapid, and sensitive detection methods. Here, a strategy is presented that enables the detection of multiple foodborne bacteria using a 3D nanostructure swab and deep learning-based Raman signal classification. The nanostructure swab efficiently captures foodborne pathogens, and the portable Raman instrument directly collects the Raman signals of captured bacteria. a deep learning algorithm has been demonstrated, 1D convolutional neural network with binary labeling, achieves superior performance in classifying individual bacterial species. This methodology has been extended to mixed bacterial populations, maintaining accuracy close to 100%. In addition, the gradient-weighted class activation mapping method is used to provide an investigation of the Raman bands for foodborne pathogens. For practical application, blind tests are conducted on contaminated kitchen utensils and foods. The proposed technique is validated by the successful detection of bacterial species from the contaminated surfaces. The use of a 3D nanostructure swab, portable Raman device, and deep learning-based classification provides a powerful tool for rapid identification (≈5 min) of foodborne bacterial species. The detection strategy shows significant potential for reliable food safety monitoring, making a meaningful contribution to public health and the food industry.

Racial/ethnic discrimination, ADH1B*3, and coping-motivated drinking among Black college students.

BACKGROUND AND OBJECTIVES: Discrimination due to race and/or ethnicity can be a pervasive stressor for Black college students in the United States beyond general negative life events and has demonstrated associations with adverse health and alcohol outcomes. Genetics may confer individual differences in the risk of drinking to cope with discrimination-related stress. This study tested whether associations of racial/ethnic discrimination with coping drinking motives and alcohol use differ as a function of a well-documented variant in the alcohol dehydrogenase 1B gene (ADH1B*3). METHODS: Cross-sectional data were obtained from 241 Black students (Mage = 20.04 [range = 18-53]; 66% female) attending a predominantly White university in the northeastern United States. Participants provided a saliva sample for genotyping and self-reported on their racial/ethnic discrimination experiences, coping drinking motives, and past-month total alcohol quantity. RESULTS: Path models demonstrated that associations of discrimination with alcohol quantity directly or indirectly through coping drinking motives did not differ as a function of ADH1B*3, after controlling for gender, age, negative life events, and potential confounding interactions of covariates with model predictors. Regardless of ADH1B*3, greater experience of negative life events was associated with higher coping drinking motives, which in turn were associated with greater alcohol quantity. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Findings represent a novel investigation into gene-environment interplay in associations of alcohol use with racial/ethnic discrimination. Findings demonstrate coping-motivated drinking associated with negative life events within Black college drinkers regardless of ADH1B*3. Future research should leverage longitudinal designs to characterize associations of genetics, stressful experiences, and coping-motivated drinking over time.

Cytokine profile and cytoskeletal changes after herpes simplex virus type 1 infection in human trabecular meshwork cells.

Uveitis caused by herpes simplex virus (HSV)-1 is characterized by increased intraocular pressure (IOP) in the presence of anterior chamber inflammation. Despite their clinical significance, the pathogenic changes associated with HSV-1 infection in trabecular meshwork (TM) cells, the key cell type regulating IOP, have not been completely elucidated. In this study, cytokine array analyses showed a significant stepwise increase in monocyte chemoattractant protein (MCP)-1 expression upon HSV-1 infection in TM cells (p < 0.05). HSV-1 infection led to downregulation of fibrogenic molecules (fibronectin, α-smooth muscle actin, connective tissue growth factor and TGF-ß1). Notably, HSV-1 infection caused a significant increase in actin stress fibres, with a twofold increase in active RhoA, which was enhanced by treatment with TGF-ß1 and inhibited by treatment with the Rho-kinase inhibitor, Y-27632. TM cells treated with MCP-1 exhibited a dose-dependent increase in actin stress fibres compared to untreated TM cells. Our study suggests that HSV-1 infection in TM cells increases cell contractile activity rather than fibrotic changes in the extracellular matrix (ECM) components. Taken together, these observations demonstrate the enhanced expression of MCP-1 and TM cell contractile activity upon HSV-1 infection and events with potential implications for the pathobiology of abrupt IOP elevation in HSV-1 anterior uveitis.

Pharmacological inhibition of androgen receptor expression induces cell death in prostate cancer cells.

The androgen receptor (AR) plays an important role in the pathogenesis and development of prostate cancer (PCa). Mostly, PCa progresses to androgen-independent PCa, which has activated AR signaling from androgen-dependent PCa. Thus, inhibition of AR signaling may be an important therapeutic target in androgen-dependent and castration-resistant PCa. In this study, we determined the anticancer effect of a newly found natural compound, sakurasosaponin (S-saponin), using androgen-dependent and castration-resistant PCa cell lines. S-saponin induces mitochondrial-mediated cell death in both androgen-dependent (LNCaP) and castration-resistant (22Rv1 and C4-2) PCa cells, via AR expression. S-saponin treatment induces a decrease in AR expression in a time- and dose-dependent manner and a potent decrease in the expression of its target genes, including prostate-specific antigen (PSA), transmembrane protease, serin 2 (TMPRSS2), and NK3 homeobox 1 (NKX3.1). Furthermore, S-saponin treatment decreases B-cell lymphoma-extra large (Bcl-xL) and mitochondrial membrane potential, thereby increasing the release of cytochrome c into the cytosol. Moreover, Bcl-xL inhibition and subsequent mitochondria-mediated cell death caused by S-saponin were reversed by Bcl-xL or AR overexpression. Interestingly, S-saponin-mediated cell death was significantly reduced by a reactive oxygen species (ROS) scavenger, N-acetylcystein. Animal xenograft experiments showed that S-saponin treatment significantly reduced tumor growth of AR-positive 22Rv1 xenografts but not AR-negative PC-3 xenografts. Taken together, for the first time, our results revealed that S-saponin induces mitochondrial-mediated cell death in androgen-dependent and castration-resistant cells through regulation of AR mechanisms, including downregulation of Bcl-xL expression and induction of ROS stress by decreasing mitochondrial membrane potential.

Structure and antifungal activity of pelgipeptins from Paenibacillus elgii against phytopathogenic fungi.

Paenibacillus elgii JCK1400 shows strong antifungal activity against various plant pathogenic fungi in vitro, but little is known about its mode of action. Four antifungal lipopeptides were isolated from P. elgii JCK1400 using bioassay-directed fractionation. Their chemical structures were determined to be pelgipeptins (PGPs) using electrospray ionization tandem mass spectrometry (ESI-MS/MS) and nuclear magnetic resonance (NMR) spectroscopy. Among the four lipopeptides, PGP-C showed the strongest mycelial growth inhibitory activity against several plant pathogenic fungi-with minimum inhibitory concentration (MIC) values ranging from 4 to 32 µg mL-1-followed by PGP-D, -A, and -B. In pot experiments, PGP-C also effectively suppressed the development of important fungal diseases in crops. In particular, PGP-C was effective in controlling tomato grey mold and wheat leaf rust, with control values of 91% and 73%, respectively, at a concentration of 125 µg mL-1. The fermentation broth of the antagonistic bacterium reduced the development of creeping bentgrass dollar spot and Kentucky bluegrass brown patch in a dose-dependent manner. However, our study on the effect of PGP-C on the fungal cell membrane-using microscopic observation with propidium iodide (PI) fluorescence-indicated that PGP-C does not target the fungal cell walls, but instead targets the cell membranes. This is the first study to report the in vitro and in vivo antifungal activity of PGP-C against various plant pathogenic fungi. Our results suggest that P. elgii JCK1400, which produces PGPs, could serve as a potential biocontrol agent for plant diseases caused by various fungi.

Clinical and radiological outcomes between biportal endoscopic decompression and microscopic decompression in lumbar spinal stenosis.

BACKGROUND CONTEXT: Numerous minimal invasive techniques treating lumbar spinal stenosis have been introduced. Clinical results using biportal endoscopic spinal surgery has recently been introduced as a treatment option for lumbar spinal stenosis. The purpose of this study was to compare the clinical and radiologic outcome between microscopic unilateral laminotomy bilateral decompression and biportal endoscopic unilateral laminotomy bilateral decompression in patients with degenerative lumbar spinal stenosis. METHOD: A total of 89 patients were evaluated for this study. Only single-level patients were enrolled for accurate comparison. Patients that underwent biportal endoscopic surgery were assigned to Group A, and patients that underwent microscopic surgery were designated Group B. Clinical outcomes were evaluated using modified Macnab criteria, Oswestry Disability Index, and Visual Analog Scale. Postoperative complications were checked until final follow up. Plain radiographs before and after surgery were compared to analyze the change of alignment. RESULT: There was a significant difference between Group A and B in VAS of back on postoperative 2 months. Other clinical measurements except for postoperative 2 months VAS of back showed no significant difference. There were no significant differences between Group A and Group B regarding preoperative and postoperative radiological findings. CONCLUSION: Two different decompression techniques preserve the spinal structure and exhibit a favorable clinical outcome and have the advantage of not causing postoperative instability in the short term follow up. Biportal endoscopic surgery may leads to less postoperative back pain than microscopic surgery, which may allow early ambulation and shorter hospitalization period.

Interaction Effects between the Cumulative Genetic Score and Psychosocial Stressor on Self-Reported Drinking Urge and Implicit Attentional Bias for Alcohol: A Human Laboratory Study.

AIMS: The current candidate gene and environment interaction (cGxE) study examined whether the effects of an experimentally manipulated psychosocial stressor on self-reported drinking urge and implicit attentional bias for alcohol cues differ as a function of a cumulative genetic score of 5-HTTLPR, MAO-A, DRD4, DAT1 and DRD2 genotypes. The current study also examined whether salivary alpha-amylase level or self-reported anxiety state mediate these cGxE effects. SHORT SUMMARY: Individuals with high cumulative genetic risk score of the five monoamergic genotypes showed greater attentional bias toward alcohol cues when exposed to a psychosocial stressor than when not exposed. METHODS: Frequent binge-drinking Caucasian young adults (N = 105; mean age = 19; 61% male) completed both the control condition and stress condition (using the Trier Social Stress Test) in order. RESULTS: Regarding attentional bias, individuals with high and medium cumulative genetic risk scores showed greater attentional bias toward alcohol stimuli in the stress condition than in the control condition, whereas, those with low genetic risk scores showed greater attentional bias toward alcohol stimuli in the control condition than in the stress condition. No mediating roles of salivary alpha-amylase and anxiety state in the cGxE effect were found. Regarding self-reported drinking urge, individuals with high cumulative genetic score reported greater drinking urge than those with low genetic score regardless of experimental conditions. CONCLUSIONS: Although replication is necessary, the findings suggest that the association of a psychosocial stressor on implicit (but not explicit, self-reported) alcohol outcomes may differ as a function of the collective effects of five monoamine genes.

Self-Medication for Sleep in College Students: Concurrent and Prospective Associations With Sleep and Alcohol Behavior.

OBJECTIVE/BACKGROUND: College students are at an increased risk for poor sleep and associated sleep problems. Emerging evidence suggests that a substantial subset of college students self-medicate with alcohol, marijuana, or over-the-counter medications to help sleep. The current study identified demographic, psychosocial, and sleep- and alcohol-related correlates of self-medication for sleep, and assessed its concurrent and prospective associations with insomnia symptoms, alcohol drinking, and negative drinking consequences. PARTICIPANTS: Undergraduate students (N = 171; mean age = 19 years [SD = 1.35], 32% male, 74% White) enrolled in a four-year university in the northeastern United States. METHODS: Data were drawn from a short-term two-wave longitudinal study. Participants completed two online surveys, separated by an average interval of 68 days (SD = 10.22). RESULTS: At Time 1, 25% of students reported using at least one substance (alcohol, marijuana, or over-the-counter medications) for sleep aid in the past two weeks. Male and older students were more likely to report using substances for sleep. Sleep aid use at Time 1 was concurrently associated with greater levels of alcohol frequency, negative drinking consequences, and insomnia symptoms. Further, sleep aid use at Time 1 was associated with an increase in negative drinking consequences from Time 1 to Time 2, but not with changes in alcohol frequency or insomnia symptoms. CONCLUSIONS: These findings indicate that substances are widely used among college students for sleep aid. Sleep aid use is associated with greater concurrent drinking and insomnia symptoms, and increases in negative drinking consequences over a short time period.

Racial discrimination, binge drinking, and negative drinking consequences among black college students: serial mediation by depressive symptoms and coping motives.

Objectives: Experiences of racial discrimination have been associated with diverse negative health outcomes among racial minorities. However, extant findings of the association between racial discrimination and alcohol behaviors among Black college students are mixed. The current study examined mediating roles of depressive symptoms and coping drinking motives in the association of perceived racial discrimination with binge drinking and negative drinking consequences. Design: Data were obtained from a cross-sectional study of Black college students attending a predominantly White institution in the northeastern US (N = 251, 66% female, mean age = 20 years). Results: Results from path analysis showed that, when potential mediators were not considered, perceived racial discrimination was positively associated with negative drinking consequences but not frequency of binge drinking. Serial multiple mediation analysis showed that depressive symptoms and in turn coping drinking motives partially mediated the associations of perceived racial discrimination with both binge drinking frequency and negative drinking consequences (after controlling for sex, age, and negative life events). Conclusions: Perceived racial discrimination is directly associated with experiences of alcohol-related problems, but not binge drinking behaviors among Black college students. Affective responses to perceived racial discrimination experiences and drinking to cope may serve as risk mechanisms for alcohol-related problems in this population. Implications for prevention and intervention efforts are discussed.

A systematic review: Candidate gene and environment interaction on alcohol use and misuse among adolescents and young adults.

BACKGROUND AND OBJECTIVES: Youth drinking is a pervasive public health concern with serious negative developmental implications. Candidate gene and environment interaction studies (cGxE) show that environmental effects on drinking behaviors may differ by individuals' genotypes. Yet little is known about whether genetic and environmental effects on drinking behaviors are developmentally specific. METHODS: This systematic review evaluated 42 cGxE studies of drinking in adolescence and young adulthood. RESULTS: Although there are mixed findings, studies of cGxE effects involving DRD4, 5-HTTLPR, DRD2, and OPRM1 genotypes showed relatively consistent patterns. The effects of under-controlled environments (eg, low levels of parental monitoring) on early and middle adolescent drinking appeared to differ across DRD2 or OPRM1 genotypes. Effects of alcohol-facilitating environments (eg, heavy drinking peers) on late adolescent and young adult drinking appeared to differ across DRD4 or OPRM1 genotypes. Interactions between 5-HTTLPR genotype with stressful environments (eg, negative life events) were found throughout adolescence and young adulthood, although there were some inconsistencies regarding the risk-conferring allele. There was limited evidence for other cGxE effects due to the small number of studies. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This review suggests that GxE findings may advance our knowledge regarding which developmentally specific conditions result in the expression of candidate genes that influence youth alcohol use and misuse. However, since a significant number of studies had small sample sizes and most studies had small effect sizes, findings need replication across independent studies with large samples. (Am J Addict 2018;XX:1-19).

Interaction between the ADH1B*3 allele and drinking motives on alcohol use among Black college students.

BACKGROUND: Black young adults have lower rates of alcohol use than other racial groups. Genetic factors may protect against drinking. Specifically, the ADH1B*3 allele is present almost exclusively in Black populations and has been protective against alcohol use and alcohol use disorder. The protective effects of the ADH1B*3 allele, however, may differ as a function of alcohol-promoting cognitions. OBJECTIVES: The current study examined whether ADH1B*3 moderated relations of drinking motives with alcohol consumption among Black college drinkers. METHODS: Participants were 241 undergraduate students of self-identified Black race (mean age = 20 years; 66% female) who reported consuming alcohol at least once in the past 30 days. RESULTS: ADH1B*3 was not significantly associated with drinking motives or drinking behaviors. However, significant, albeit small, interaction effects of ADH1B*3 with drinking motives on drinking behavior were found; the presence of an ADH1B*3 allele protected against greater drinking quantity among students with high social motives (incidence rate ratio [IRR] = 0.95, 95% CI [0.92, 0.99]) and against frequent drinking among students with low coping motives (IRR = 1.06, 95% CI [1.01, 1.11]). CONCLUSION: These findings represent a novel demonstration of genetic modulation of alcohol-related cognitions within Black college drinkers, although replication is needed. Results represent an initial step toward better characterizing individual differences in associations of drinking motives with drinking behavior, with potential implications for interventions aimed at motivational processes in alcohol use.

Gastrostomy tube placement for long-term oral drug administration in non-human primates.

BACKGROUND: Non-human primates (NHPs) are often used as recipients in preclinical transplantation research that in most cases involves administration of various drugs including immunosuppressants. Long-term oral drug administration, particularly tacrolimus, is challenging in the transplant recipient NHPs. Oral drug administration method using the mixture of drug and fruit juice has been used in NHPs, but this is not always effective in all monkeys. To those monkeys who are poorly compliant, oral drug administration in restraint or administration using gastrostomy tube should be necessary. The aim of this study was to compare the efficacy of between oral drug administration in restraint and administration using gastrostomy tube and to report complications and solutions to overcome the problems related to gastrostomy tube for long-term oral drug dosing in rhesus monkeys. METHODS: Fifteen of 4- to 5-year-old male and female healthy rhesus monkeys weighing 5.0-6.8 kg were used as recipients for porcine pancreatic islet transplantation. Oral drug administration in restraint was used for four monkeys, and gastrostomy tube was placed to other 11 monkeys (8-French Feeding tube, n=6; Tri-Funnel Replacement Gastrostomy tube, n=5). Oral immunosuppressive drugs such as sirolimus and tacrolimus were administered through the tube. The efficacy and the extent of ease for administration and related complications were compared between two groups. RESULTS AND CONCLUSIONS: The complication of gastrostomy included a transient inflammation in the skin and peritonitis caused by a leakage around implantation site (one case), which could be overcome by changing suture method and tube type to interlocking box suture and Tri-Funnel Replacement Gastrostomy tube, respectively. Despite these complications, oral drug administration using gastrostomy tube allowed us to perform accurate dosage of drug administration and to reduce the stress that both the monkey and the researcher may experience. Taken together, this study showed that gastrostomy tube placement is a better alternative to oral drug administration in restraint for long-term oral drug administration in rhesus monkeys who tend to refuse to eat the mixture of drug and fruit juice.

The interaction between the dopamine receptor D4 (DRD4) variable number tandem repeat polymorphism and perceived peer drinking norms in adolescent alcohol use and misuse.

Peer drinking norms are arguably one of the strongest correlates of adolescent drinking. Prospective studies indicate that adolescents tend to select peers based on drinking (peer selection) and their peers' drinking is associated with changes in adolescent drinking over time (peer socialization). The present study investigated whether the peer selection and socialization processes in adolescent drinking differed as a function of the dopamine receptor D4 (DRD4) variable number tandem repeat genotype in two independent prospective data sets. The first sample was 174 high school students drawn from a two-wave 6-month prospective study. The second sample was 237 college students drawn from a three-wave annual prospective study. Multigroup cross-lagged panel analyses of the high school student sample indicated stronger socialization via peer drinking norms among carriers, whereas analyses of the college student sample indicated stronger drinking-based peer selection in the junior year among carriers, compared to noncarriers. Although replication and meta-analytic synthesis are needed, these findings suggest that in part genetically determined peer selection (carriers of the DRD4 seven-repeat allele tend to associate with peers who have more favorable attitudes toward drinking and greater alcohol use) and peer socialization (carriers' subsequent drinking behaviors are more strongly associated with their peer drinking norms) may differ across adolescent developmental stages.

Interaction between ADH1B*3 and alcohol-facilitating social environments in alcohol behaviors among college students of african descent.

BACKGROUND AND OBJECTIVES: Although alcohol-facilitating social environmental factors, such as alcohol offers and high perceived peer drinking norms, have been extensively studied as determinants of college drinking, their role among college students of African descent remains understudied. Furthermore, gene-environment interaction research suggests that the effects of alcohol-facilitating environments may differ as a function of genetic factors. Specifically, the alcohol dehydrogenase gene's ADH1B*3 allele, found almost exclusively in persons of African descent, may modulate the association of risky social environments with alcohol behaviors. The current study examined whether the ADH1B*3 allele attenuated the relationship between alcohol-facilitating environments (ie, alcohol offers and perceived peer drinking norms) and alcohol behaviors. METHOD: Participants were 241 undergraduate students who self-identified as being of African descent (mean age = 20 years [SD = 4.11]; 66% female). RESULTS: Significant interaction effects of ADH1B*3 with alcohol offers were found on alcohol use frequency (incidence rate ratio [IRR] = 1.14) and on drinking consequences (IRR = 1.21). ADH1B*3 also interacted with perceived peer norms on drinking consequences (IRR = 1.41). Carriers of the ADH1B*3 allele drank less frequently and experienced fewer negative consequences than non-carriers when exposed to lower levels of alcohol offers and perceived peer drinking. In contrast, in high alcohol-facilitating environments, no protective genetic effect was observed. DISCUSSION AND CONCLUSION: This study demonstrates that ADH1B*3 may protect college students of African descent against alcohol outcomes, although only in low alcohol-facilitating environments. SCIENTIFIC SIGNIFICANCE: Findings add to the growing body of knowledge regarding genetic and social determinants of alcohol behaviors among college students of African descent. (Am J Addict 2017;26:349-356).

Induction, management, and complications of streptozotocin-induced diabetes mellitus in rhesus monkeys.

BACKGROUND: Diabetes mellitus (DM) model using streptozotocin (STZ) which induces chemical ablation of ß cell in the pancreas has been widely used for various research purposes in non-human primates. However, STZ has been known to have a variety of adverse effects such as nephrotoxicity, hepatotoxicity, and even mortality. The purpose of this study is to report DM induction by STZ, toxicity associated with STZ and procedure and complication of exogenous insulin treatment for DM management in rhesus monkeys (Macaca mulatta) that are expected to be transplanted with porcine islets within 2 months. METHODS: Streptozotocin (immediately dissolved in normal saline, 110 mg/kg) was slowly infused via central catheter for 10 minutes in 22 rhesus monkeys. Clinical signs, complete blood count and blood chemistry were monitored to evaluate toxicity for 1 week after STZ injection. Monkey basal C-peptides were measured and intravenous glucose tolerance test was performed to confirm complete induction of DM. Exogenous insulin was subcutaneously injected to maintain blood glucose in diabetic rhesus monkeys and the complications were recorded while in insulin treatment. RESULTS: Severe salivation and vomiting were observed within 1 hour after STZ injection in 22 rhesus monkeys. One monkey died at 6 hours after STZ injection and the reason for the death was unknown. Pancreatitis was noticed in one monkey after STZ injection, but the monkey recovered after 5 days by medical treatment. Serum total protein and albumin decreased whereas the parameters for the liver function such as aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase significantly increased (P<.05) after STZ injection, but they were resolved within 1 week. Azotemia was not observed. Monkey fasting C-peptide levels after STZ injection were <0.1 ng/mL in 18 rhesus monkeys, but 0.34, 0.22, 0.16 ng/mL in three monkeys, respectively. The value of daily insulin requirement was 0.92±0.26IU/kg/d (range=0.45-1.29) in the monkeys. Diabetic ketoacidosis was observed in one rhesus monkeys, but the monkey recovered after 24 hours by fluid and insulin treatment. CONCLUSIONS: Streptozotocin was effective for inducing DM in rhesus monkeys, but various adverse effects such as pancreatitis, liver toxicity or death were observed. Therefore, careful and suitable medical managements should be implemented to eliminate the risks of mortality and severe adverse effects.

Heterogeneous Charge-Transfer Nanorods by Strained Melt-Molding Lithography.

Hetero-nanorods consisting of two charge-transfer (CT) complexes were fabricated by the strained melt-molding lithography. Utilizing the lowered melting temperature by the formation of eutectic mixture, various well-defined CT complex nanorods can be easily fabricated by soft-lithography-assisted melt crystallization below 100 degrees C. Hetero-nanorods were fabricated by selective doping of the secondary CT complex at defects induced by applying the uniaxial strain.

Intra-articular injection, subacromial injection, and hydrodilatation for primary frozen shoulder: a randomized clinical trial.

BACKGROUND: The aim of this prospective randomized study was to compare the efficacy of 3 injection methods, intra-articular injection, subacromial injection, and hydrodilatation (HD), in the treatment of primary frozen shoulder. METHODS: Patients with primary frozen shoulder were randomized to undergo intra-articular injection (n = 29), subacromial injection (n = 29), or HD (n = 28). Evaluations using a visual analog scale for pain, Simple Shoulder Test, Constant score, and passive range of shoulder motion were completed before treatment and 1 month, 3 months, and 6 months after treatment. RESULTS: Among the 3 injection methods for primary frozen shoulder, HD resulted in a greater range of motion in forward flexion and external rotation, a lower visual analog scale score for pain after 1 month, and better outcomes for all functional scores after 1 month and 3 months of follow-up. However, there were no significant differences in any clinical outcomes among the 3 groups in the final follow-up at 6 months. CONCLUSIONS: Although HD yielded more rapid improvement, the 3 injection methods for primary frozen shoulder resulted in similar clinical improvement in the final follow-up at 6 months.

Transoral endoscopic thyroidectomy via the tri-vestibular routes: results of a preclinical cadaver feasibility study.

The concept of natural orifice transluminal endoscopic surgery (NOTES) is an emerging experimental alternative to conventional surgery that eliminates skin incisions using an endoscope passed through a natural orifice (e.g., mouth, urethra, or anus). This study was designed to evaluate the feasibility and safety of thyroid resection via an entirely transoral tri-vestibular route using endoscopy, and to introduce NOTES to the head and neck area of medicine. We performed ten complete endoscopic thyroid lobectomies with central lymph node dissection via a tri-vestibular approach in fresh-frozen cadavers. A 5-mm endoscope with a deflectable tip was used to visualize the surgical field. Three cannulas were inserted through the midline and bilateral incision sites in the vestibule to position the instruments and endoscope. We refined and described the surgical technique in each step using video clips. We identified and preserved neighboring critical structures during surgery. We also confirmed that there were no obvious remnant thyroid tissues and no injury to the neighboring structures after exploration. The transoral tri-vestibular approach seems to provide a good view and surgical field for endoscopic thyroidectomy. However, the transoral approach for thyroidectomy remains experimental, and the detailed surgical technique should be refined via further clinical studies.