Congenital retinoschisis: successful collapse with photocoagulation

We report a case of progressive congenital retinoschis is where the schisis cavity collapsed following argon laser photocoagulation. Despite reports to the contrary, we feel that in the absence of significant vitreous or inner layer traction, photocoagulation applied as light burns in the schisis cavity may be beneficial in collapsing the cavity. Whether or not this collapse of the schisis cavity reduces the risk of rhegmatogenous retinal detachment is unclear.     

Low incidence of p53 mutations in betel quid and tobacco chewing-associated oral squamous carcinoma from India

Mutations of the p53 tumor suppressor gene have been found to be the single most frequent event in human cancers. In India and other southeast Asian countries tobacco chewing with betel quid was attributed to be the major factor in oral carcinogenesis. We have analyzed 72 untreated primary oral squamous cell carcinomas (SCCs) for mutations in the tumor suppressor gene p53 exons 4-9 by PCR-SSCP and DNA sequencing. Sequencing analysis revealed 16 missense mutations, one silent mutation in codon 307 and four A to G substitution polymorphism in codon 213. The incidence of p53 mutation was 21% (15 of 72) excluding the polymorphism and the silent mutation. Eight mutations were clustered in codons 266-282 of exon 8. Of the total mutation events 37.5% were G to A transitions and 31.3% were G to T transversions. These results indicate the possible involvement of tobacco derived nitrosamines and their adducts in the genesis of oral cancer among Indians.     

Induction of long-term protective effects against heterologous challenge in SIVhu-infected macaques

A group of three rhesus macaques were inoculated with SIV isolated from a human (SIVhu) accidentally exposed and infected with SIVsm. Extensive sequence analyses of SIVhu obtained from the human and macaques following infection indicated the presence of truncated nef. Not only did nef fail to repair itself in vivo postinfection (p.i.), but instead, further mutations added additional stop codons with increasing time p.i. Infection of these animals was associated with minimal acute viral replication, followed by undetectable plasma viral loads and only intermittent PCR detection up to 5 years p.i. The three SIVhu infected and three control monkeys were then challenged with the heterologous highly pathogenic SHIV89.6p. All three controls became infected and showed rapid declines in peripheral CD4(+) lymphocytes, disease, and death at 10 and 32 weeks p.i., respectively. In contrast, all three animals previously infected with SIVhu are healthy and exhibit stable CD4(+) lymphocyte levels and undetectable plasma viral loads at >20 months post-SHIV89. 6p challenge. Only transient, low levels of SHIV replication were noted in these animals. Whereas responses to SIVgag/pol were noted, no evidence for SIV/SHIV envelope cross-reactivity was detected by antibody or CTL analyses, suggesting that the protective immune mechanisms to the heterologous challenge isolate were most likely not directed to envelope but rather to other viral determinants.     

Skin penetration and retention of L-Ascorbic acid 2-phosphate using multilamellar vesicles

Transdermal formulation of L-ascorbic acid 2-phosphate magnesium salt (A2P) was prepared using multilamellar vesicles (MLV). A2P was either physically mixed with or entrapped into three different MLVs of neutral, cationic, and anionic liposome vesicles. For the preparation of neutral MLVs, phosphatidylcholine (PC) and cholesterol (CH) were used. For cationic and anionic MLVs, dioleoyl-trimethylammonium-propane and dimyristoyl glycerophosphate were added as surface charge inducers, respectively, in addition to PC and CH. Particle size of the three A2P-loaded MLVs was submicron, and polydispersity index revealed homogenous distribution of the prepared MLVs except neutral ones. Skin penetration study with hairless mouse skin showed that both physical mixtures of A2P with empty MLVs and A2P-loaded MLVs increased penetration of the drug compared to aqueous A2P solution. During the penetration, however, significant amount of the drug was metabolized into L-ascorbic acid, which has no beneficial effect on stimulation of hair growth. Out of the physical mixtures and A2P-loaded MLVs tested, physical mixture of A2P with empty cationic MLV resulted in the greatest skin penetration and retention in hairless mouse skin.     

Bone Marrow Adipose Tissue and Skeletal Health

Purpose of Review

To summarize and discuss recent progress and novel signaling mechanisms relevant to bone marrow adipocyte formation and its physiological/pathophysiological implications for bone remodeling.

Recent Findings

Skeletal remodeling is a coordinated process entailing removal of old bone and formation of new bone. Several bone loss disorders such as osteoporosis are commonly associated with increased bone marrow adipose tissue. Experimental and clinical evidence supports that a reduction in osteoblastogenesis from mesenchymal stem cells at the expense of adipogenesis, as well as the deleterious effects of adipocyte-derived signaling, contributes to the etiology of osteoporosis as well as bone loss associated with aging, diabetes mellitus, post-menopause, and chronic drug therapy. However, this view is challenged by findings indicating that, in some contexts, bone marrow adipose tissue may have a beneficial impact on skeletal health.

Summary

Further research is needed to better define the role of marrow adipocytes in bone physiology/pathophysiology and to determine the therapeutic potential of manipulating mesenchymal stem cell differentiation.

     

A review on structural genomics approach applied for drug discovery against three vector-borne viral diseases: Dengue,Chikungunya and Zika

Virus Genes - Structural genomics involves the advent of three-dimensional structures of the genome encoded proteins through various techniques available. Numerous structural genomics research...     

Positive selection of the peripheral B cell repertoire in gut-associated lymphoid tissues

Gut-associated lymphoid tissues (GALTs) interact with intestinal microflora to drive GALT development and diversify the primary antibody repertoire; however, the molecular mechanisms that link these events remain elusive. Alicia rabbits provide an excellent model to investigate the relationship between GALT, intestinal microflora, and modulation of the antibody repertoire. Most B cells in neonatal Alicia rabbits express V(H)n allotype immunoglobulin (Ig)M. Within weeks, the number of V(H)n B cells decreases, whereas V(H)a allotype B cells increase in number and become predominant. We hypothesized that the repertoire shift from V(H)n to V(H)a B cells results from interactions between GALT and intestinal microflora. To test this hypothesis, we surgically removed organized GALT from newborn Alicia pups and ligated the appendix to sequester it from intestinal microflora. Flow cytometry and nucleotide sequence analyses revealed that the V(H)n to V(H)a repertoire shift did not occur, demonstrating the requirement for interactions between GALT and intestinal microflora in the selective expansion of V(H)a B cells. By comparing amino acid sequences of V(H)n and V(H)a Ig, we identified a putative V(H) ligand binding site for a bacterial or endogenous B cell superantigen. We propose that interaction of such a superantigen with V(H)a B cells results in their selective expansion.     

The past,present and future of service delivery in genetic counseling: Keeping up in the era of precision medicine

Precision medicine aims to approach disease treatment and prevention with consideration of the variability in genes, environment, and lifestyle for each person. This focus on the individual is also key to the practice of genetic counseling, whereby foundational professional values prioritize informed and autonomous patient decisions regarding their genetic health. Genetic counselors are ideally suited to help realize the goals of the precision medicine. However, a limited genetic counseling workforce at a time in which there is a rapidly growing need for services is challenging the balance of supply and demand. This article provides historical context to better understand what has informed traditional models of genetic counseling and considers some of the current forces that require genetic counselors to adapt their practice. New service delivery models can improve access to genetic healthcare by overcoming geographical barriers, allowing genetic counselors to see a higher volume of patients and supporting other healthcare providers to better provide genetic services to meet the needs of their patients. Approaches to genetic counseling service delivery are considered with a forward focus to the challenges and opportunities that lie ahead for genetic counselors in this age of precision health.