A platform of integrative studies from in vitro to in vivo experiments: Towards drug development for ischemic retinopathy

Pathologic angiogenesis induced by hypoxia is a hallmark of ischemic retinopathy including diabetic retinopathy and retinopathy of prematurity. These 2 diseases affect substantial number of working population and preterm babies, respectively, resulting in visual deterioration. It is essential for novel therapeutics for ischemic retinopathy to demonstrate the potency in reducing pathologic angiogenesis and the safety without definite toxicity on the retina and the whole body. In this review, we suggest a novel platform of integrative studies from in vitro to in vivo experiments on angiogenesis and toxicity with the aim of accelerating and facilitating the development of novel therapeutic agents for ischemic retinopathy. Robust in vitro and in vivo studies with bridging microfluidic and ex vivo systems help researchers to evaluate the efficacy and anticipate the toxicity of candidate drugs. We hope that novel therapeutic approach based on this platform will be developed in near future and reduce the incidence of vision loss from ischemic retinopathy.     

The Future of Polycystic Kidney Disease Research—As Seen By the 12 Kaplan Awardees

Polycystic kidney disease (PKD) is one of the most common life-threatening genetic diseases. Jared J. Grantham, M.D., has done more than any other individual to promote PKD research around the world. However, despite decades of investigation there is still no approved therapy for PKD in the United States. In May 2014, the University of Kansas Medical Center hosted a symposium in Kansas City honoring the occasion of Dr. Grantham''s retirement and invited all the awardees of the Lillian Jean Kaplan International Prize for Advancement in the Understanding of Polycystic Kidney Disease to participate in a forward-thinking and interactive forum focused on future directions and innovations in PKD research. This article summarizes the contributions of the 12 Kaplan awardees and their vision for the future of PKD research.     

Uric Acid and Cardiovascular Events: A Mendelian Randomization Study

Obesity and diets rich in uric acid–raising components appear to account for the increased prevalence of hyperuricemia in Westernized populations. Prevalence rates of hypertension, diabetes mellitus, CKD, and cardiovascular disease are also increasing. We used Mendelian randomization to examine whether uric acid is an independent and causal cardiovascular risk factor. Serum uric acid was measured in 3315 patients of the Ludwigshafen Risk and Cardiovascular Health Study. We calculated a weighted genetic risk score (GRS) for uric acid concentration based on eight uric acid–regulating single nucleotide polymorphisms. Causal odds ratios and causal hazard ratios (HRs) were calculated using a two-stage regression estimate with the GRS as the instrumental variable to examine associations with cardiometabolic phenotypes (cross-sectional) and mortality (prospectively) by logistic regression and Cox regression, respectively. Our GRS was not consistently associated with any biochemical marker except for uric acid, arguing against pleiotropy. Uric acid was associated with a range of prevalent diseases, including coronary artery disease. Uric acid and the GRS were both associated with cardiovascular death and sudden cardiac death. In a multivariate model adjusted for factors including medication, causal HRs corresponding to each 1-mg/dl increase in genetically predicted uric acid concentration were significant for cardiovascular death (HR, 1.77; 95% confidence interval, 1.12 to 2.81) and sudden cardiac death (HR, 2.41; 95% confidence interval, 1.16 to 5.00). These results suggest that high uric acid is causally related to adverse cardiovascular outcomes, especially sudden cardiac death.     

Sentinel node biopsy in uro-oncology: A history of the development of a promising concept

Lymph node staging is important in many urologic malignancies. The lack of a sufficiently accurate noninvasive lymph node staging modality has proven to be challenging as most urologic malignancies rely on surgical lymph node removal for regional staging. Penile cancer has been a model disease for the development of the sentinel node concept, which has subsequently been successfully adapted to breast cancer and melanoma studies. Currently, the sentinel node technique is standardized in many centers and under development for new indications. The introduction of near-infrared cameras and fluorescence techniques has paved the way for robot-assisted laparoscopic sentinel node biopsies in prostate cancer, urinary bladder cancer, and renal cancer. Fluorescence techniques have increased visual guidance towards lymph nodes during surgery and have challenged previously established templates for surgical lymph node removal. This review discusses the history of our understanding of the lymphatic system and the development of the sentinel node concept and highlights the importance of early and minimally invasive regional lymph node staging. Contemporary data on sentinel node biopsy in each of the urologic malignancies are assessed. Current trends towards robot-assisted sentinel lymph node removal are discussed, and the diagnostic accuracy and oncologic safety of sentinel node procedures are addressed. In an era of several new sentinel node indications, the importance of proper case selection, protocolled regimen, consequent follow-up, and back-up strategies in the case of radiotracer-silent or nonvisualized regions is stressed.     

A cross-sectional study of the knowledge and attitude of medical laboratory personnel regarding continuing professional development

Background:

Continuing professional development (CPD) in Medical Laboratory Scientists (MLS) is aimed at equipping laboratory professionals with the necessary skills to enhance practice. The laboratory scientists are usually the first contact between the patient and health care system in aspects of diagnosis and monitory of diseases. As such, it becomes imperative to assess the knowledge of laboratory personnel regarding CPD.

Materials and Methods:

Self-administered questionnaires were distributed to 200 laboratory personnel''s attending the maiden CPD workshop organized by the Association of MLS in Jos the Plateau state capital.

Results:

One hundred and thirty-five (82 males and 53 females) of the 200 administered questionnaires were returned. Only 32 of them (23.7%) attended CPD program in the last 1 year with 10 (7.5%) engaging in online CPD. Five (3.7%) of the respondents had the privilege to attend an international CPD. Majority (95.2%) of the respondents identified CPD as an essential component of professional career development. Lack of sponsorship was identified as a major setback in CPD efficiency by 93.8% of respondents. About 58 (46.4%) noted that poor attendance in CPD workshops was due to unavailability of policy guideline for CPD. One hundred and twenty (95.2%) of respondents had an aim of improving their skills after attending CPD workshops.

Conclusion:

The overall attitude of Nigerian MLS toward attending CPD workshop is poor; however, the knowledge regarding the importance of CPD is adequate. There exists a gap between sponsorship for CPD by various institutions and MLS.     

Targeted deletion of Vglut2 expression in the embryonal telencephalon promotes an anxiolytic phenotype of the adult mouse

Background

Anxiety is a natural emotion experienced by all individuals. However, when anxiety becomes excessive, it contributes to the substantial group of anxiety disorders that affect one in three people and thus are among the most common psychiatric disorders. Anxiolysis, the reduction of anxiety, is mediated via several large groups of therapeutical compounds, but the relief is often only temporary, and increased knowledge of the neurobiology underlying anxiety is needed in order to improve future therapies.

Aim

We previously demonstrated that mice lacking forebrain expression of the Vesicular glutamate transporter 2 (Vglut2) from adolescence showed a strong anxiolytic behaviour as adults. In the current study, we wished to analyse if removal of Vglut2 expression already from mid-gestation of the mouse embryo would give rise to similar anxiolysis in the adult mouse.

Methods

We produced transgenic mice lacking Vglut2 from mid-gestation and analysed their affective behaviour, including anxiety, when they had reached adulthood.

Results

The transgenic mice lacking Vglut2 expression from mid-gestation showed certain signs of anxiolytic behaviour, but this phenotype was not as prominent as when Vglut2 was removed during adolescence.

Conclusion

Our results suggest that both embryonal and adolescent forebrain expression of Vglut2 normally contributes to balancing the level of anxiety. As the neurobiological basis for anxiety is similar across species, our results in mice may help improve the current understanding of the neurocircuitry of anxiety, and hence anxiolysis, also in humans.     

两种硫辛酸对映体对胚胎体外发育的影响

目的：探讨(R)-硫辛酸和(S)-硫辛酸对胚胎体外发育的影响。方法解冻复苏卵裂期胚胎,分别在含不同浓度(R)-硫辛酸和(S)-硫辛酸的GⅡ培养基微滴中培养,观察各组的桑胚率、致密化率、囊胚率和优质囊胚率。结果硫辛酸可提高胚胎体外发育率,(R)-硫辛酸浓度10×10-9 mol/m3组桑胚率、致密化率、囊胚率和优质囊胚率分别达到了59.2%,55.1%,49.0%和54.2%,均高于其他浓度组（P<0.01）。(R)-硫辛酸浓度10×10-9 mol/m3组的桑胚率、致密化率和优质胚胎率均高于(S)-硫辛酸10×10-9 mol/m3组（P<0.05）。结论硫辛酸对胚胎体外发育具有促进作用,特别是对桑胚率和囊胚率具有显著的影响。(R)-硫辛酸10×10-9 mol/m3组的效果最好。     

Orthodontic treatment in children to prevent sleep-disordered breathing in adulthood

The purpose of this article is to review human craniofacial growth and development, especially the growth of the mandible, to clarify the relationship between obstructive sleep apnea (OSA) syndrome and craniofacial abnormality, and finally, to propose the hypothesis that negative pressure produced in the chest of the OSA child inhibits the growth of the mandible. Recently, the development of diagnosis and treatment of OSA syndrome has progressed rapidly; however, the prevention of OSA syndrome was merely seen. Craniofacial abnormality is reported as one of the causes of OSA syndrome. If craniofacial abnormality is determined only by genetics, it is difficult to manage the craniofacial skeleton to prevent OSA syndrome. The role of epigenetic factors on craniofacial growth and development is still controversial. However, if we stand on the functional matrix hypothesis, we can manage not only growth of the mandible but also the craniofacial skeleton as a whole. The author proposes the hypothesis that the negative pressure produced in the chest prohibits the growth of the mandible even if the patients have a capacity for growth and development; therefore, if this negative pressure disappears because of the removal of the tonsil and/or adenoids or by an orthodontic treatment to make a patency of the airway, the mandible may grow normally, and we can prevent or reduce a number of OSA syndromes in the future.