MKK4 and metastasis suppression: a marriage of signal transduction and metastasis research

MAP kinase kinase 4 (MKK4) is a member of the stress-activated protein kinase (SAPK) signaling cascade and is involved in the regulation of many cellular processes. We have recently demonstrated a functional role for MKK4 in the suppression of metastases. In this review, we discuss the established cellular and biochemical functions of MKK4, as well as a new function for MKK4 as a metastasis suppressor gene. Because of the importance of signaling studies to this translational work, a detailed example of the strategy and tools that can be employed to define the biochemical mechanism of MKK4-mediated metastasis suppression is presented. Finally, the potential therapeutic utility of these findings is discussed.     

Diagnostic procedure in osteodystrophia deformans Paget

Simultaneous scintigraphic and X-ray examination has been evaluated in 30 patients with Paget's disease for estimation of extension and activity of the disease. Scintigraphy produces a comprehensive picture of the pathophysiologic condition. When compared with X-rays the procedure is more economic with regards to cost, time and radiation dosage. Therefore, the use of radioisotopes for evaluation of the skeleton is strongly recommended for follow-up examination in Paget's disease.     

Rheumatic and Musculoskeletal Diseases (RMDs) Public Awareness Program of Georgia 2019–2020

Clinical Rheumatology - The program’s goal is to launch the platform of positive perspectives for people who are suffering from/working in rheumatic and musculoskeletal diseases through the...     

A cross-sectional study of newborns over a 20-year period in Szeged,Hungary

Objective: Records of metric data of birth, serve not only the medical needs of the newborn baby, but are also indicators to assess the status of public health.

Methods: This is a retrospective study of 4946 newborns (singleton: 2508 boys and 2365 girls) born in 1989 and in 2009 at the Department of Obstetrics and Gynaecology of the University of Szeged. We aimed as to compare and map the metrical changes over 20 years, and to describe the averages of four body parameters of the normal birth weight (2500–4000?g) subgroup (3993 singleton babies) in both years. Statistical analysis was performed with SPSS 17.0.

Results: In 1989, the mean birth weight was 3223.770?±?559.595?g, birth length 49.551?±?2.729?cm, chest circumference 32.181?±?2.231?cm, and head circumference 34.122?±?1.688?cm. In 2009, the birth weight was 3309.673?±?582.630?g, birth length 49.515?±?2.658?cm, chest circumference 32.736?±?2.392?cm and head circumference 33.854?±?1.768?cm. The mean birth weight, chest circumference and the maximum value of birth weight have thus increased. The mean maternal age shifted to 30.21?±?4.863 years, which is an increase of 3.57 years in 20 years.

Conclusion: The body parameters of newborns changed significantly between 1989 and 2009. As underlying causes changes in eating habits and lifestyle of the mother are to be mentioned.     

Pathophysiological characterization of drug hypersensitivity to tribenoside

Background

Tribenoside is a semisynthetic sugar derivative that is mainly indicated for treatment of chronic venous insufficiency. Up to 10% of patients treated by tribenoside can suffer from skin side effects. The adverse effects usually present as angioedema, urticaria, or maculopapular exanthema. The pathophysiology of the reaction has not as yet been elucidated.

Methods

In this study, we examined 22 patients with drug eruptions caused by tribenoside. Patch tests were performed to investigate in vivo cellular reactions. Laboratory investigations were carried out by lymphocyte transformation tests and basophil activation tests.

Results

We found a positive patch test reaction to tribenoside in one patient. The lymphocyte transformation test elicited a borderline positive reaction in one patient, and the basophil activation test gave a clearly positive reaction in another patient.

Conclusion

The diagnosis of drug hypersensitivity reactions is a challenge. Both delayed and immediate immunologic response may play a role in the etiology of tribenoside-induced exanthemas. Our investigation and results indicate that benzoic acid could be the antigenic determinant in drug hypersensitivity to tribenoside.     

Partial‐volume modeling reveals reduced gray matter in specific thalamic nuclei early in the time course of psychosis and chronic schizophrenia

The structural complexity of the thalamus, due to its mixed composition of gray and white matter, make it challenging to disjoint and quantify each tissue contribution to the thalamic anatomy. This work promotes the use of partial‐volume‐based over probabilistic‐based tissue segmentation approaches to better capture thalamic gray matter differences between patients at different stages of psychosis (early and chronic) and healthy controls. The study was performed on a cohort of 23 patients with schizophrenia, 41 with early psychosis and 69 age and sex‐matched healthy subjects. Six tissue segmentation approaches were employed to obtain the gray matter concentration/probability images. The statistical tests were applied at three different anatomical scales: whole thalamus, thalamic subregions and voxel‐wise. The results suggest that the partial volume model estimation of gray matter is more sensitive to detect atrophies within the thalamus of patients with psychosis. However all the methods detected gray matter deficit in the pulvinar, particularly in early stages of psychosis. This study demonstrates also that the gray matter decrease varies nonlinearly with age and between nuclei. While a gray matter loss was found in the pulvinar of patients in both stages of psychosis, reduced gray matter in the mediodorsal was only observed in early psychosis subjects. Finally, our analyses point to alterations in a sub‐region comprising the lateral posterior and ventral posterior nuclei. The obtained results reinforce the hypothesis that thalamic gray matter assessment is more reliable when the tissues segmentation method takes into account the partial volume effect.     

Cognitive mapping style relates to posterior–anterior hippocampal volume ratio

As London taxi drivers acquire “the knowledge” and develop a detailed cognitive map of London, their posterior hippocampi (pHPC) gradually increase in volume, reflecting an increasing pHPC/aHPC volume ratio. In the mnemonic domain, greater pHPC/aHPC volume ratios in young adults have been found to relate to better recollection ability, indicating that the balance between pHPC and aHPC volumes might be reflective of cross‐domain individual differences. Here, we examined participants' self‐reported use of cognitive map‐based navigational strategies in relation to their pHPC/aHPC hippocampal volume ratio. We find that greater reported cognitive map use was related to significantly greater posterior, relative to anterior, hippocampal volume in two separate samples of young adults. Further, greater reported cognitive map usage correlated with better performance on a self‐initiated navigation task. Together, these data help to advance our understanding of differences between aHPC and pHPC and the greater role of pHPC in spatial mapping.     

A Community Study of SARS-CoV-2 Detection by RT-PCR in Saliva: A Reliable and Effective Method

Efficient, wide-scale testing for SARS-CoV-2 is crucial for monitoring the incidence of the infection in the community. The gold standard for COVID-19 diagnosis is the molecular analysis of epithelial secretions from the upper respiratory system captured by nasopharyngeal (NP) or oropharyngeal swabs. Given the ease of collection, saliva has been proposed as a possible substitute to support testing at the population level. Here, we used a novel saliva collection device designed to favour the safe and correct acquisition of the sample, as well as the processivity of the downstream molecular analysis. We tested 1003 nasopharyngeal swabs and paired saliva samples self-collected by individuals recruited at a public drive-through testing facility. An overall moderate concordance (68%) between the two tests was found, with evidence that neither system can diagnose the infection in 100% of the cases. While the two methods performed equally well in symptomatic individuals, their discordance was mainly restricted to samples from convalescent subjects. The saliva test was at least as effective as NP swabs in asymptomatic individuals recruited for contact tracing. Our study describes a testing strategy of self-collected saliva samples, which is reliable for wide-scale COVID-19 screening in the community and is particularly effective for contact tracing.     

Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation

Olfactory receptors are G protein-coupled receptors that mediate olfactory chemosensation and serve as chemosensors in other tissues. We find that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs). Olfr78 is expressed in the renal juxtaglomerular apparatus, where it mediates renin secretion in response to SCFAs. In addition, both Olfr78 and G protein-coupled receptor 41 (Gpr41), another SCFA receptor, are expressed in smooth muscle cells of small resistance vessels. Propionate, a SCFA shown to induce vasodilation ex vivo, produces an acute hypotensive response in wild-type mice. This effect is differentially modulated by disruption of Olfr78 and Gpr41 expression. SCFAs are end products of fermentation by the gut microbiota and are absorbed into the circulation. Antibiotic treatment reduces the biomass of the gut microbiota and elevates blood pressure in Olfr78 knockout mice. We conclude that SCFAs produced by the gut microbiota modulate blood pressure via Olfr78 and Gpr41.