db/db mice exhibit severe wound-healing impairments compared with other murine diabetic strains in a silicone-splinted excisional wound model

The pathophysiology of diabetic wound healing and the identification of new agents to improve clinical outcomes continue to be areas of intense research. There currently exist more than 10 different murine models of diabetes. The degree to which wound healing is impaired in these different mouse models has never been directly compared. We determined whether differences in wound impairment exist between diabetic models in order to elucidate which model would be the best to evaluate new treatment strategies. Three well-accepted mouse models of diabetes were used in this study: db/db, Akita, and streptozocin (STZ)-induced C57BL/6J. Using an excisional model of wound healing, we demonstrated that db/db mice exhibit severe impairments in wound healing compared with STZ and Akita mice. Excisional wounds in db/db mice show a statistically significant delay in wound closure, decreased granulation tissue formation, decreased wound bed vascularity, and markedly diminished proliferation compared with STZ, Akita, and control mice. There was no difference in the rate of epithelialization of the full-thickness wounds between the diabetic or control mice. Our results suggest that splinted db/db mice may be the most appropriate model for studying diabetic wound-healing interventions as they demonstrate the most significant impairment in wound healing. This study utilized a novel model of wound healing developed in our laboratory that stents wounds open using silicone splints to minimize the effects of wound contraction. As such, it was not possible to directly compare the results of this study with other studies that did not use this wound model.     

Mundgesundheitskompetenz von Menschen mit Migrationshintergrund – Erste Auswertungen der MuMi-Studie

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Erste Studien heben den Migrationshintergrund von Menschen in Deutschland als eigenständigen Risikofaktor für eine...     

Mathematical model of volume kinetics and renal function after burn injury and resuscitation

This paper presents a mathematical model of blood volume kinetics and renal function in response to burn injury and resuscitation, which is applicable to the development and non-clinical testing of burn resuscitation protocols and algorithms. Prior mathematical models of burn injury and resuscitation are not ideally suited to such applications due to their limited credibility in predicting blood volume and urinary output observed in wide-ranging burn patients as well as in incorporating contemporary knowledge of burn pathophysiology. Our mathematical model consists of an established multi-compartmental model of blood volume kinetics, a hybrid mechanistic-phenomenological model of renal function, and novel lumped-parameter models of burn-induced perturbations in volume kinetics and renal function equipped with contemporary knowledge on burn-related physiology and pathophysiology. Using the dataset collected from 16 sheep, we showed that our mathematical model can be characterized with physiologically plausible parameter values to accurately predict blood volume kinetic and renal function responses to burn injury and resuscitation on an individual basis against a wide range of pathophysiological variability. Pending validation in humans, our mathematical model may serve as an effective basis for in-depth understanding of complex burn-induced volume kinetic and renal function responses as well as development and non-clinical testing of burn resuscitation protocols and algorithms.     

Differential pharmacology between the guinea-pig and the gorilla 5-HT1D receptor as probed with isochromans (5-HT1D-selective ligands).

1. Both the 5-HT1D and 5-HT1B receptors are implicated in migraine pathophysiology. Recently isochromans have been discovered to bind primate 5-HT1D receptors with much higher affinity than 5-HT1B receptors. In the guinea-pig, a primary animal model for anti-migraine drug testing, however, isochromans bound the 5-HT1D receptor with lower affinity than the gorilla receptor. 2. This species-specific pharmacology was investigated, using site-directed mutagenesis on cloned guinea-pig receptors heterologously expressed in human embryonic kidney 293 cells. Mutations of threonine 100 and arginine 102 at the extracellular side of transmembrane II of the guinea-pig 5-HT1D receptor to the corresponding primate residues, isoleucine and histidine, respectively, enhanced its affinity for isochromans to that of the gorilla receptor, with little effects on its affinities for serotonin, sumatriptan and metergoline. Free energy change from the R102H mutation was about twice as much as that from the T100I mutation. 3. For G protein-coupling, serotonin marginally enhanced GTPgamma35S binding in membranes expressing the guinea-pig 5-HT1D receptor and its mutants, but robustly in membranes expressing the gorilla receptor. Sumatriptan enhanced GTPgamma35S binding in the latter nearly as much as serotonin, and several isochromans by 30-60% of serotonin. 4. We discovered key differences in the function and binding properties of guinea-pig and gorilla 5-HT1D receptors, and identified contributions of I100 and H102 of primate 5-HT1D receptors to isochroman binding. Among common experimental animals, only the rabbit shares I100 and H102 with primates, and could be useful for studying isochroman actions in vivo.     

Stereotactic approach to skull-base lesions

With improved knowledge of the anatomy and increased collaboration between the neurosurgeon and the otolaryngologist, successful surgical resection of skull-based tumors is being achieved with reduced mortality and morbidity. In spite of this, there remains a group of patients in whom an alternate surgical approach of stereotaxis may be indicated. This group of patients includes those in whom only biopsy is required, or those in whom brachytherapy using high-intensity (125)I is planned because the patients' general condition is not good enough to undergo open surgical resection of the tumor or the tumor is unresectable or the patient refuses open surgery. This article presents a preliminary report on stereotactic approach to skull base lesions with special emphasis on the technique.     

Improving pediatric emergency department physicians’ adherence to clinical practice guidelines on the diagnosis and management of group A beta-hemolytic streptococcal pharyngitis—a cross-sectional study

Introduction

Pharyngitis is one of the major and commonly seen presentations in pediatric emergency departments. While it could be caused by both bacterial and viral pathogens, antibiotics are improperly prescribed regardless of the pathogen. Inappropriate usage of antibiotics has risen the concern of microbial resistance and the need for stricter guidelines. Many guidelines have been validated for this reason, and the Centor score (Modified/McIsaac) is most commonly implemented. This study aims to assess the adherence and enumerate the reasons behind the suboptimal adherence to guidelines (Centor/McIsaac score) of pediatric emergency department physicians in the diagnosis and management of GABHS pharyngitis to lay the groundwork for future actions and to employ educational programs and implement local guidelines for the prevention of the development of multi-drug resistant microorganisms.

Methodology

We surveyed pediatric emergency department physicians of ten teaching hospitals of Riyadh, Saudi Arabia. We used convenient sampling and estimated a sample size of 170 physicians, and interns and medical centers without pediatric emergency department were excluded from the study. Elements of the Centor score (Modified/McIsaac) were used as a part of the assessment of physicians’ knowledge of the guidelines. Adherence was assessed by requiring the participants to answer questions regarding their usage of diagnostic means when they suspect a bacterial cause of pharyngitis, as recommended by the guidelines.

Results

A total of 243 physicians answered the questionnaire, 43 consultants (17.6%) and 200 non-consultants (82.4%). On the knowledge score, 9.1% scored 0, and the majority of both groups, 46.5%, earned a score of 1. The remainder 44.4%, earned a score of 2. Adherence to guidelines was defined as when diagnostic tests (throat culture or rapid antigen detection test) were always requested prior to prescribing antibiotics when acute bacterial pharyngitis was suspected. Only 27.3% (n?=?67) of our sample are adherent to guidelines, whereas the majority, 72.7% (n?=?175), are non-adherent. Several factors were assessed as reasons for lack of adherence.

Conclusion

Lack of knowledge and adherence to guidelines is prevalent in our setting, with awareness, knowledge, and behavior of physicians playing as major factors behind this low adherence. Studies should aim towards the assessment of adherence towards locally developed guidelines.

     

HIV Prevalence and Related Behaviors Among People Who Inject Drugs in Iran from 2010 to 2020

AIDS and Behavior - Injection drug use has been the leading route of HIV transmission in Iran. We assessed HIV prevalence, risk behaviors, and uptake of prevention services among people who inject...     

Marginal adaptation of zirconia complete-coverage fixed dental restorations made from digital scans or conventional impressions: A systematic review and meta-analysis

Statement of problemIntraoral scanners have been increasingly used in recent years. However, the accuracy of digital scans as it affects marginal adaptation is unclear.PurposeThe purpose of this systematic review and meta-analysis was to compare the marginal adaptation of single-unit zirconia crowns fabricated with digital scans or with conventional impressions.Material and methodsThe electronic databases PubMed (MEDLINE), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (ISI), Scopus, and EMBASE were searched and complemented by a manual search. Risks of bias were assessed by using a modified methodological index for nonrandomized studies (MINORS). Mean ±standard deviation (SD) values of marginal accuracy of studies were extracted for both methods. Mean marginal difference and 95% confidence interval (CI) were calculated to evaluate the marginal accuracy of each method. Pooled data were statistically analyzed by using a random-effect model.ResultsSeventeen studies were used to perform the meta-analysis. Subgroup analysis was performed based on intraoral scanners. Standardized mean marginal difference and 95% CI of each subgroup were as follows: Lava: -0.85 μm (95% CI: -1.67, -0.03) (P=.043); CEREC: -1.32 μm (95% CI: -2.06, -0.59) (P<.001); iTero: -0.44 μm (95% CI: -1.35, 0.47) (P=.338); TRIOS: -1.26 μm (95% CI: -2.02, -0.51) (P=.001); unknown scanner: -0.21 μm (95% CI: -1.14, 0.72); all studies: -0.89 μm (95% CI: -1.24, -0.54) (P<.001).ConclusionsDigital scanning of prepared teeth for single-unit zirconia restorations resulted in better marginal accuracy than conventional techniques using elastomeric impression materials.     

Negative biomarker-based male fertility evaluation: sperm phenotypes associated with molecular-level anomalies

Biomarker-based sperm analysis elevates the treatment of human infertility and ameliorates reproductive performance in livestock. The negative biomarker-based approach focuses on proteins and ligands unique to defective spermatozoa, regardless of their morphological phenotype, lending itself to analysis by flow cytometry (FC). A prime example is the spermatid specific thioredoxin SPTRX3/TXNDC8, retained in the nuclear vacuoles and superfluous cytoplasm of defective human spermatozoa. Infertile couples with high semen SPTRX3 are less likely to conceive by assisted reproductive therapies (ART) and more prone to recurrent miscarriage while low SPTRX3 has been associated with multiple ART births. Ubiquitin, a small, proteolysis-promoting covalent posttranslational protein modifier is found on the surface of defective posttesticular spermatozoa and in the damaged protein aggregates, the aggresomes of spermiogenic origin. Semen ubiquitin content correlates negatively with fertility and conventional semen parameters, and with sperm binding of lectins LCA (Lens culinaris agglutinin; reveals altered sperm surface) and PNA (Arachis hypogaea/peanut agglutinin; reveals acrosomal malformation or damage). The Postacrosomal Sheath WWI Domain Binding Protein (PAWP), implicated in oocyte activation during fertilization, is ectopic or absent from defective human and animal spermatozoa. Consequently, FC-parameters of PAWP correlate with ART outcomes in infertile couples and with fertility in bulls. Assays based on the above biomarkers have been combined into multiplex FC semen screening protocols, and the surface expression of lectins and ubiquitin has been utilized to develop nanoparticle-based bull semen purification method validated by field artificial insemination trials. These advances go hand-in-hand with the innovation of FC-technology and genomics/proteomics-based biomarker discovery.