Diabetes mellitus, blood glucose and the risk of heart failure: A systematic review and meta-analysis of prospective studies.

BACKGROUND AND AIM: The strength of the association between diabetes and risk of heart failure has differed between previous studies and the available studies have not been summarized in a meta-analysis. We therefore quantified the association between diabetes and blood glucose and heart failure in a systematic review and meta-analysis. METHODS AND RESULTS: PubMed and Embase databases were searched up to May 3rd 2018. Prospective studies on diabetes mellitus or blood glucose and heart failure risk were included. A random effects model was used to calculate summary relative risks (RRs) and 95% confidence intervals (CIs). Seventy seven studies were included. Among the population-based prospective studies, the summary RR for individuals with diabetes vs. no diabetes was 2.06 (95% CIs: 1.73-2.46, I2 = 99.8%, n = 30 studies, 401495 cases, 21416780 participants). The summary RR was 1.23 (95% CI: 1.15-1.32, I2 = 78.2%, n = 10, 5344 cases, 91758 participants) per 20 mg/dl increase in blood glucose and there was evidence of a J-shaped association with nadir around 90 mg/dl and increased risk even within the pre-diabetic blood glucose range. Among the patient-based studies the summary RR was 1.69 (95% CI: 1.57-1.81, I2 = 85.5%, pheterogeneity<0.0001) for diabetes vs. no diabetes (n = 41, 100284 cases and >613925 participants) and 1.25 (95% CI: 0.89-1.75, I2 = 95.6%, pheterogeneity<0.0001) per 20 mg/dl increase in blood glucose (1016 cases, 34309 participants, n = 2). In the analyses of diabetes and heart failure there was low or no heterogeneity among the population-based studies that adjusted for alcohol intake and physical activity and among the patient-based studies there was no heterogeneity among studies with ≥10 years follow-up. CONCLUSIONS: These results suggest that individuals with diabetes are at an increased risk of developing heart failure and there is evidence of increased risk even within the pre-diabetic range of blood glucose.

[Burnout in psychiatric physicians. Results of an empirical study]. / Burnout bei psychiatrisch tätigen Arztinnen und Arzten. Resultate einer empirischen Untersuchung.

OBJECTIVE: The study aimed at assessing burnout in psychiatrists and psychiatric residents, all of them working in the Canton of Zurich, Switzerland, and at identifying some of its correlates. METHODS: Potentially burnout- related demographic, work, leisure activities, and personality (Munich Personality Test) variables were studied in three subgroups of 307 probands--psychiatric residents, psychiatrists working as staff members or in leading positions in psychiatric institutions, and psychiatrists working in private practice--the degree of burnout having been assessed with the Tedium Measure (TM). RESULTS: The mean TM score of all probands of 2.9 (SD = 0.7) was on a low level, high TM scores (> 3.5) were indicated by 57 (18%) participants. Significantly higher TM scores were indicated by psychiatric residents, who also scored higher with regard to neuroticism and lower with regard to frustration tolerance on MPT. CONCLUSIONS: Neuroticism alone explained a substantial proportion of the total TM variance in individual groups. Work-related variables turned out to be of a small importance only, whereas no influence could be demonstrated for different leisure activities.

Management of vocal fold scar with autologous fat implantation: perceptual results.

Vocal fold scar disrupts the mucosal wave and interferes with glottic closure. Treatment involves a multidisciplinary approach that includes voice therapy, medical management, and sometimes surgery. We reviewed the records of the first eight patients who underwent autologous fat implantation for vocal fold scar. Information on the etiology of scar, physical findings, and prior interventions were collected. Videotapes of videostroboscopic findings and perceptual voice ratings [Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS)] were randomized and analyzed independently by four blinded observers. Etiology of scar included mass excision (7), vocal fold stripping (3), congenital sulcus (2), and hemorrhage (1). Prior surgical procedures performed included thyroplasty (1), autologous fat injection (9), excision of scar (2), and lysis of adhesions (2). Strobovideolaryngoscopy: Statistically significant improvement was found in glottic closure, mucosal wave, and stiffness (P = 0.05). Perceptual ratings (GRBAS): Statistically significant improvement was found in all five parameters, including overall Grade, Roughness, Breathiness, Asthenia, and Strain (P = 0.05). Patients appear to have improved vocal fold function and quality of voice after autologous fat implantation in the vocal fold. Autologous fat implantation is an important adjunctive procedure in the management of vocal fold scar, and a useful addition to the armamentarium of the experienced phonomicrosurgeon.

Botulinum toxin in otolaryngology: a review of its actions and opportunities for use.

Botulinum toxin has several important properties that make it an ideal chemical denervator. These include its high degree of specificity for the neuromuscular junction, its ability to induce temporary and reversible denervation, and its limited degree of side effects and complications. Botulinum toxin is being used safely in a wide variety of clinical settings by many different specialists. In otolaryngologic practice, it is being administered for the treatment of at least a dozen conditions, including various dysphonias, dystonias, and spasms as well as torticollis, facial nerve paralysis, and hyperkinetic facial lines. Studies have shown that botulinum toxin injections have a high rate of success in temporarily relieving symptoms.

Sulfidoleukotriene generation from peripheral blood leukocytes of horses affected with insect bite dermal hypersensitivity.

Sulfidoleukotrienes (sLT) generated in vitro after incubation of equine peripheral blood leukocytes (PBL) with different inducing agents were determined in 18 healthy and 16 insect bite dermal hypersensitivity (IDH)-affected horses. PBL from these 32 horses were stimulated with Concanavalin A, Parascaris equorum, Culicoides nubeculosus and Simulium extracts, and with a six-Grass mix. The cells of all but four horses generated sLT after incubation with Concanavalin A; these four horses did also not produce sLT with the other inducing agents. Of the 28 remaining horses (12 affected with IDH and 16 healthy), all but three generated sLT with the P. equorum extract. The six-Grass mix did not induce sLT production in any of the tested horses. sLT generation with Concanavalin A and Parascaris was statistically not different between IDH-affected and healthy horses. PBL of the diseased horses, however, produced significantly more sLT with the Culicoides (p < 0.01) and Simulium (p < 0.05) extracts than those of the healthy animals. Additionally, sLT generation with the Culicoides extract was measured at different times of the year in one IDH-affected animal and remained high even in winter, when the horse was asymptomatic. sLT and histamine release were determined in 10 horses in parallel. Positive correlations of 0.81 and 0.82 for Concanavalin A and Parascaris (p < 0.01 and p < 0.05, respectively), and of 0.95 and 0.94 for Culicoides and Simulium (p < 0.01) were found between sLT and histamine release. These results indicate that, alike in humans, sLT are released in vitro from equine basophils along with histamine in response to various stimuli and that immediate type hypersensitivity reactions to Culicoides and Simulium are often involved in the pathogenesis of IDH. Thus, sLT generation from equine basophils offers an in vitro diagnostic tool for IDH even in sensitised but asymptomatic horses.

Maxillary perfusion during Le Fort I osteotomy after ligation of the descending palatine artery.

PURPOSE: Controversy exists regarding management of the descending palatine artery (DPA) during Le Fort I osteotomy. Some surgeons advocate preserving the DPA, and others ligate the vessels. The purpose of this study was to evaluate maxillary gingival blood flow (GBF) during Le Fort I osteotomy in a sample of patients with and without ligation of the DPA. PATIENTS AND METHODS: Using a prospective randomized clinical study, we enrolled a study sample composed of 34 patients undergoing Le Fort I osteotomy. The patients were randomly assigned to either study group 1 (16) (DPA ligated) or group 2 (18) (DPA preserved). To measure maxillary GBF during the operation, we used laser Doppler flowmetry (LDF). The predictor variable was status of DPA management (ligated or preserved). The outcome variable was change in GBF over time. RESULTS: (DPA). Before ligation (or simulated ligation) of the DPA, the mean GBF for groups 1 and 2 was 11.4 +/- 8.6 and 11.9 +/- 9.4 mL/min/100 g tissue, respectively (P = .88). After ligation of the DPA in group 1, the mean GBF was 10.0 +/- 7.7 mL/min/100 g tissue. At the corresponding time in group 2 (DPA preserved), the mean GBF was 12.6 +/- 9.4 mL/min/100 g tissue. The difference in mean GBF between groups 1 and 2 was not statistically significant (P = .43). CONCLUSION: There were no statistically significant differences in mean maxillary GBF between patients having the DPA ligated and those having the DPA preserved as measured using LDF during Le Fort I osteotomy.

The effect of local anesthesia with vasoconstrictor on gingival blood flow during Le Fort I osteotomy.

PURPOSE: In earlier studies, it has been documented that maxillary gingival blood flow (GBF) decreased significantly during the intraoperative course of a Le Fort I osteotomy. It was not clear, however, whether the observed decrease in GBF was caused by the osteotomy or by the use of local anesthetic with vasoconstrictor (LA + V). The purpose of this study was to measure the effect of LA + V on GBF during Le Fort I osteotomy using laser Doppler flowmetry (LDF). PATIENTS AND METHODS: Using a randomized clinical trial study design, patients undergoing Le Fort I osteotomy were assigned to either a treatment (group 1, LA + V used) or a control group (group 2, LA + V not used). The predictor variable was group assignment (LV + V used or not used). The outcome variable was mean maxillary GBF. Maxillary GBF was recorded at predetermined times during the operation. Other study variables included age, sex, single- or double-jaw surgery, estimated blood loss, direction and magnitude of maxillary movements, temperature, pulse, mean blood pressure, O2 saturation, and duration of operation. RESULTS: There were 19 patients in group 1 (LA + V used) and 15 patients in group 2 (LA + V not used). In both groups, mean maxillary GBF decreased significantly during the operation (group 1, 33.3 +/- 13.1 to 16.9 +/- 16.1 mL/ min/100 g tissue, P = .015; and group 2, 48.2 +/- 17.1 to 15.5 +/- 7.6 mL/min/100 g tissue, P = .001). The decrease in GBF occurred much earlier in group 1. By an average of 2.3 hours into the operation, the mean GBF was equivalent in both study groups (group 1, 10.6 +/- 8.6, and group 2, 13.1 +/- 9.4 mL/min/100 g tissue, P = .44). CONCLUSIONS: The results of this study confirm earlier findings that mean maxillary GBF decreases significantly during the intraoperative course of a Le Fort I osteotomy. In addition, LA + V significantly affects GBF during the early phase of the operation. Its effect, however, dissipates between the time of soft tissue dissection and maxillary downfracture.

Synthesis and conformational analysis by 1H NMR and restrained molecular dynamics simulations of the cyclic decapeptide [Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly].

The design of enzyme mimics with therapeutic and industrial applications has interested both experimental and computational chemists for several decades. Recent advances in the computational methodology of restrained molecular dynamics, used in conjunction with data obtained from two-dimensional 1H NMR spectroscopy, make it a promising method to study peptide and protein structure and function. Several issues, however, need to be addressed in order to assess the validity of this method for its explanatory and predictive value. Among the issues addressed in this study are: the accuracy and generizability of the GROMOS peptide molecular mechanics force field; the effect of inclusion of solvent on the simulations; and the effect of different types of restraining algorithms on the computational results. The decapeptide Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly, which corresponds to the sequence of ACTH1-10, has been synthesized, cyclized, and studied by two-dimensional 1H NMR spectroscopy. Restrained molecular dynamics (RMD) and time-averaged restrained molecular dynamics (TARMD) simulations were carried out on four different distance-geometry starting structures in order to determine and contrast the behavior of cyclic ACTH1-10 in vacuum and in solution. For the RMD simulations, the structures did not fit the NOE data well, even at high values of the restraining potential. The TARMD simulation method, however, was able to give structures that fit the NOE data at high values of the restraining potential. In both cases, inclusion of explicit solvent molecules in the simulation had little effect on the quality of the fit, although it was found to dampen the motion of the cyclic peptide. For both simulation techniques, the number and size of the NOE violations increased as the restraining potential approached zero. This is due, presumably, to inadequacies in the force field. Additional TARMD vacuum-phase simulations, run with a larger memory length or with a larger sampling size (16 additional distance-geometry structures), yielded no significantly different results. The computed data were then analyzed to help explain the sparse NOE data and poor chymotryptic activity of the cyclic peptide. Cyclic ACTH1-10, which contains the functional moieties of the catalytic triad of chymotrypsin, was evaluated as a potential mimic of chymotrypsin by measurement of the rate of hydrolysis of esters of L- and D-phenylalanine. The poor rate of hydrolysis is attributed to the flexibility of the decapeptide, the motion of the side chains, which result in the absence of long-range NOEs, the small size of the macrocycle relative to that of the substrate, and the inappropriate orientation of the Gly, His, and Ser residues. The results demonstrate the utility of this method in computer-aided molecular design of cyclic peptides and suggest structural modifications for future work based on a larger and more rigid peptide framework.

Are head, neck and facial injuries markers of domestic violence?

Few data exist regarding the relationship between the location of injuries and the presence of domestic violence. This study of 127 people at an inner-city hospital emergency department found that most patients had head, neck and facial injuries. Although only 23 percent of patients with such injuries were victims of domestic violence, 94.4 percent of victims of domestic violence had head, neck and facial injuries. The study results indicate that head, neck and facial injuries could be markers of domestic violence.

DNA binding specificity of the basic-helix-loop-helix protein MASH-1.

Despite the high degree of sequence similarity in their basic-helix-loop-helix (BHLH) domains, MASH-1 and MyoD are involved in different biological processes. In order to define possible differences between the DNA binding specificities of these two proteins, we investigated the DNA binding properties of MASH-1 by circular dichroism spectroscopy and by electrophoretic mobility shift assays (EMSA). Upon binding to DNA, the BHLH domain of MASH-1 underwent a conformational change from a mainly unfolded to a largely alpha-helical form, and surprisingly, this change was independent of the specific DNA sequence. The same conformational transition could be induced by the addition of 20% 2,2,2-trifluoroethanol. The apparent dissociation constants (KD) of the complexes of full-length MASH-1 with various oligonucleotides were determined from half-saturation points in EMSAs. MASH-1 bound as a dimer to DNA sequences containing an E-box with high affinity KD = 1.4-4.1 x 10(-14) M2). However, the specificity of DNA binding was low. The dissociation constant for the complex between MASH-1 and the highest affinity E-box sequence (KD = 1.4 x 10(-14) M2) was only a factor of 10 smaller than for completely unrelated DNA sequences (KD = approximately 1 x 10(-13) M2). The DNA binding specificity of MASH-1 was not significantly increased by the formation of an heterodimer with the ubiquitous E12 protein. MASH-1 and MyoD displayed similar binding site preferences, suggesting that their different target gene specificities cannot be explained solely by differential DNA binding. An explanation for these findings is provided on the basis of the known crystal structure of the BHLH domain of MyoD.

Intraoperative assessment of maxillary perfusion during Le Fort I osteotomy.

Intraoperative maxillary blood flow was measured using laser Doppler flowmetry (LDF) in two groups of patients undergoing orthognathic surgery. Group 1 (n = 14) consisted of patients undergoing Le Fort I osteotomy and group 2 (n = 8) consisted of patients undergoing isolated mandibular osteotomies. In group 1, the mean gingival blood flow (GBF) decreased significantly over time during the course of the operation from 29.5 mL/min/100 g of tissue to 13.2 mL/min/100 g of tissue (P = .0001). The mean GBF did not change significantly over time in group 2 (P = .39). The results of this study demonstrate that 1) LDF may be used to measure intraoperative GBF during Le Fort I osteotomy with an acceptable level of variability, and 2) maxillary GBF decreased significantly over time during Le Fort I osteotomy procedures.