X-linked recessive chondrodysplasia punctata: spectrum of arylsulfatase E gene mutations and expanded clinical variability

Partial trisomy of the long arm of chromosome 10 is a well-defined but rare syndrome. Clinical features of this chromosomopathy are a distinctive dysmorphic appearance, developmental delay, growth retardation, and in some cases, abnormalities of the extremities and renal, cardiac and ocular anomalies. This report describes a neonate with symmetric growth retardation and multiple dysmorphic features, in whom chromosomal analysis revealed a partial trisomy of chromosome 10q with a monosomy of the 13q34 region. The phenotype shares many common features with previously published cases. In addition to the typical features, our case also shows renal hypoplasia with early renal insufficiency and some genital anomalies.     

Circadian rhythm of glucose utilization in the pineal body of rats of different ages

Employing quantitative autoradiography, pineal body glucose utilization (GU) was measured in daytime or at night in prepubertal (aged 1 month), adult (aged 3 months), and mature (over 12 months old) rats. In prepubertal and adult rats, in daytime, GU values within the pineal tissue were homogeneously distributed around 65 mol glucose/100 g per min. In prepubertal animals no significant variations in GU were observed between daytime and nocturnal measurements. A circadian metabolic rhythmicity was evident in adult rats, with a GU peak measured at 2 a.m. In mature animals, GU also varied between day and night, with an increment in the relative difference between the two values. The present investigation is the first to demonstrate that circadian metabolic rhythmicity is absent before sexual maturation while it is enhanced in 12-month-old rats. These changes in pineal energy metabolism with advancing age are intriguing in view of the concept that the pineal gland may be involved in functional changes occurring during the process of aging.     

Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis

In this work, we propose that for further studies of the physiopathology and treatment for inflammatory bowel diseases, an integral view of the conditions, including the triad of microbiota–heat shock proteins (HSPs)–probiotics, ought to be considered. Microbiota is the complex microbial flora that resides in the gut, affecting not only gut functions but also the health status of the whole body. Alteration in the microbiota’s composition has been implicated in a variety of pathological conditions (e.g., ulcerative colitis, UC), involving both gut and extra-intestinal tissues and organs. Some of these pathologies are also associated with an altered expression of HSPs (chaperones) and this is the reason why they may be considered chaperonopathies. Probiotics, which are live microorganisms able to restore the correct, healthy equilibrium of microbiota composition, can ameliorate symptoms in patients suffering from UC and modulate expression levels of HSPs. However, currently probiotic therapy follows ex-adiuvantibus criteria, i.e., treatments with beneficial effects but whose mechanism of action is unknown, which should be changed so the probiotics needed in each case are predetermined on the basis of the patient’s microbiota. Consequently, efforts are necessary to develop diagnostic tools for elucidating levels and distribution of HSPs and the microbiota composition (microbiota fingerprint) of each subject and, thus, guide specific probiotic therapy, tailored to meet the needs of the patient. Microbiota fingerprinting ought to include molecular biology techniques for sequencing highly conserved DNA, e.g., genes encoding 16S RNA, for species identification and, in addition, quantification of each relevant microbe.     

Oral mucosa produces cytokines and factors influencing osteoclast activity and endothelial cell proliferation, in patients with osteonecrosis of jaw after treatment with zoledronic acid

Objectives

The intravenous injection of bisphosphonates, currently used as treatment for osteoporosis, bone Paget’s disease, multiple myeloma, or bone metastases, can cause jaw bone necrosis especially in consequence of trauma. The present research aimed to clarify the mechanisms underlying bone necrosis, exploring involvement of the oral mucosa “in vivo.”

Patients and methods

Specimens of oral mucosa were removed from bisphosphonate-treated patients with or without jaw bone necrosis. In mucosa specimens, expression was evaluated of: cytokines involved in the inflammatory process, factors involved in osteoclast activity, i.e., receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin, a factor involved in cell proliferation, namely hydroxymethylglutaryl coenzyme A reductase, and a factor involved in angiogenesis, namely vascular endothelial growth factor (VEGF).

Results

Interleukin (IL)-6 and the RANK/osteoprotegerin ratio were significantly elevated in mucosa from patients with versus without jaw necrosis, whereas hydroxymethylglutaryl coenzyme A reductase and VEGF were significantly decreased.

Conclusions

Our results suggest that mucosa, stimulated by bisphosphonate released from the bone, can contribute to the development of jaw necrosis, reducing VEGF, and producing IL-6 in consequence of hydroxymethylglutaryl coenzyme A reductase reduction. In turn, IL-6 stimulates osteoclast activity, as shown by the increased RANKL/osteoprotegerin ratio.

Clinical relevance

The results of this study suggest the importance of evaluating during bisphosphonate treatment the production of IL-6, RANKL, osteoprotegerin, and VEGF, in order to monitor the jaw osteonecrosis onset. To avoid repeated mucosa excisions, the determination of these factors could be carried out in crevicular fluid.     

Differential recognition of a tyrosine-dependent signal in the basolateral and endocytic pathways of thyroid epithelial cells

Trafficking of receptors is of crucial importance for the physiology of most exocrine and endocrine organs. It is not known yet if the same mechanisms are used for sorting in the exocytic and endocytic pathways in the different epithelial tissues. In this work, we have used a deletion mutant of the human neurotrophin receptor p75(hNTR) that is normally localized on the apical membrane when expressed in Madin-Darby canine kidney cells. This internal 57-amino acid deletion of the cytoplasmic tail leads to a relocation of the protein from the apical to the basolateral membrane and to rapid and efficient endocytosis. These events are mediated by a signal localized within 9 amino acids of the mutated cytoplasmic tail that is strictly dependent on a tyrosine residue (Tyr-308). We have analyzed the basolateral sorting efficiency and endocytic capacity of this signal in Fischer rat thyroid (FRT) cells, in which basolateral and endocytic determinants have not yet been identified. We found that this targeting signal can mediate efficient transport to the basolateral membrane also in FRT cells with similar tyrosine dependence as in MDCK cells. In contrast to MDCK cells, this Tyr-based signal was not able to mediate coated pits localization and endocytosis in FRT cells. These data represent the first characterization of basolateral/endocytic signals in thyroid epithelial cells. Furthermore, our results indicate that requirements for tyrosine-dependent basolateral sorting signals are conserved among cell lines from different tissues but that the recognition of the colinear endocytic signal is tissue specific.     

What's the hold up? Factors contributing to delays in discharge of trauma patients after medical clearance

Background

One area of potential savings in healthcare spending is the identification of nonmedical delays in discharge. The purpose of this study was to identify factors associated with discharge delays.

Methods

All patients admitted to our trauma center over a 1-year period with a social work consult were retrospectively evaluated to identify delays in discharge after medical clearance.

Results

Over half of our patients experienced a delay in discharge. Age was not associated with delay in discharge. Higher injury severity score, intensive care unit admission, and hospital length of stay greater than 1 week were all associated with increased delays in discharge. Other factors such as disposition to a rehabilitation/nursing facility and mechanism of injury were also associated with a nonmedical delay.

Conclusions

We have identified nonmedical factors associated with delays in discharge. Strategies using these data could be used to improve discharge planning and may help decrease healthcare costs.     

Prevalence and risk factors for HIV-1 infection in rural Kilimanjaro region of Tanzania: Implications for prevention and treatment

Background  

Variability in stages of the HIV-1 epidemic and hence HIV-1 prevalence exists in different areas in sub-Saharan Africa. The purpose of this study was to investigate the magnitude of HIV-1 infection and identify HIV-1 risk factors that may help to develop preventive strategies in rural Kilimanjaro, Tanzania.