Management of nail psoriasis by topical drug delivery: a pharmaceutical perspective.

The management of nail psoriasis is an arduous task owing to the disease manifestations and anatomical structure of the nail plate. Although various treatment therapies are available for nail psoriasis, topical therapy is contemplated as one of the most favorable options as systemic therapies are accompanied by numerous side effects that result in patient incompliance. The topical formulations including creams, gels, ointments, and nail lacquers have been used as delivery systems for various antipsoriatic drugs. Among these, nail lacquers emerge to be promising and patient friendly formulations. However, the major defiance with topical delivery is inefficacious penetration of drug through impenetrable keratinized nail plate to reach the target sites: nail matrix and nail bed. Therefore, in order to obtain effectual drug delivery systems that can retain/remain on the nail plate for a prolonged period of time and deliver the drug across it, systematic approaches like quality by design (QbD) need to be followed so that the desired quality can be "built in" the system rather than to rely solely on retrograde evaluation. Furthermore, more advances in research are still required to develop a validated animal model so as to determine the efficacy of the formulation and to establish a mathematical model that can help in predicting the desirable attributes of the formulation and permeation of various molecules through the nail plate.

Indications of Intestinal Transplantation.

"The intestinal transplantation is reserved for patients with life-threatening complications of permanent intestinal failure or underlying gastrointestinal disease. The choice of the allograft for a particular patient depends on several factors and the presence of concurrent organ failure, and availability of the donor organs, and specialized care. Combined liver and intestinal transplant allows for patients who have parenteral nutrition-associated liver disease a possibility of improved quality of life and nutrition as well as survival. Intestinal transplantation has made giant strides over the past few decades to the present era where current graft survivals are comparable with other solid organ transplants."

Prophylactic effect of lamivudine on chemotherapy-induced hepatitis B virus reactivation in patients with solid tumour: A meta-analysis.

Hepatitis B virus (HBV) reactivation is a remarkable risk during the chemotherapy for solid tumour patients. Nucleos(t)ide analogues (NAs) are recommended as prophylaxis for the reactivation of HBV infection in some cancer patients prior to systemic chemotherapy. Therefore, we performed a meta-analysis aiming to determine the efficacy of prophylactic lamivudine on prevention of HBV reactivation and its related negative outcomes among solid tumour patients with chronic HBV infection receiving systemic chemotherapy. The primary outcome was HBV reactivation, and the secondary outcomes were HBV-related hepatitis, chemotherapy disruption, mortality and tyrosine-methio-nine-aspartate-aspartate (YMDD) mutations. Twelve original researches involving 1,101 patients were analysed in this study. The relative risk of HBV reactivation in patients with lamivudine prophylaxis was significantly lower than that without prophylaxis (RR = 0.17, 95% CL: 0.10-0.29, p < .00001). Lamivudine prophylaxis reduced the relative risk of hepatitis (p < .00001), chemotherapy disruptions (p = .01) and mortality (p = .08) due to HBV reactivation. Lamivudine prophylaxis is effective in reducing HBV reactivation and its related negative outcomes, such as hepatitis and chemotherapy disruption and mortality among chemotherapeutic solid tumour patients with chronic HBV infection. Future studies should lay more emphasis on the early HBV screening, mode of treatment and duration of NAs prophylaxis among solid tumour patients receiving chemotherapy.

The hydrolethalus syndrome protein HYLS-1 links core centriole structure to cilia formation.

Centrioles are subcellular organelles composed of a ninefold symmetric microtubule array that perform two important functions: (1) They build centrosomes that organize the microtubule cytoskeleton, and (2) they template cilia, microtubule-based projections with sensory and motile functions. We identified HYLS-1, a widely conserved protein, based on its direct interaction with the core centriolar protein SAS-4. HYLS-1 localization to centrioles requires SAS-4 and, like SAS-4, HYLS-1 is stably incorporated into the outer centriole wall. Unlike SAS-4, HYLS-1 is dispensable for centriole assembly and centrosome function in cell division. Instead, HYLS-1 plays an essential role in cilia formation that is conserved between Caenorhabditis elegans and vertebrates. A single amino acid change in human HYLS1 leads to a perinatal lethal disorder termed hydrolethalus syndrome, and we show that this mutation impairs HYLS-1 function in ciliogenesis. HYLS-1 is required for the apical targeting/anchoring of centrioles at the plasma membrane but not for the intraflagellar transport-dependent extension of the ciliary axoneme. These findings classify hydrolethalus syndrome as a severe human ciliopathy and shed light on the dual functionality of centrioles, defining the first stably incorporated centriolar protein that is not required for centriole assembly but instead confers on centrioles the capacity to initiate ciliogenesis.

Centromere identity maintained by nucleosomes assembled with histone H3 containing the CENP-A targeting domain.

Active centromeres are marked by nucleosomes assembled with CENP-A, a centromere-specific histone H3 variant. The CENP-A centromere targeting domain (CATD), comprised of loop 1 and the alpha2 helix within the histone fold, is sufficient to target histone H3 to centromeres and to generate the same conformational rigidity to the initial subnucleosomal heterotetramer with histone H4 as does CENP-A. We now show in human cells and in yeast that depletion of CENP-A is lethal, but recruitment of normal levels of kinetochore proteins, centromere-generated mitotic checkpoint signaling, chromosome segregation, and viability can be rescued by histone H3 carrying the CATD. These data offer direct support for centromere identity maintained by a unique nucleosome that serves to distinguish the centromere from the rest of the chromosome.

Unstable microtubule capture at kinetochores depleted of the centromere-associated protein CENP-F.

Centromere protein F (CENP-F) (or mitosin) accumulates to become an abundant nuclear protein in G2, assembles at kinetochores in late G2, remains kinetochore-bound until anaphase, and is degraded at the end of mitosis. Here we show that the absence of nuclear CENP-F does not affect cell cycle progression in S and G2. In a subset of CENP-F depleted cells, kinetochore assembly fails completely, thereby provoking massive chromosome mis-segregation. In contrast, the majority of CENP-F depleted cells exhibit a strong mitotic delay with reduced tension between kinetochores of aligned, bi-oriented sister chromatids and decreased stability of kinetochore microtubules. These latter kinetochores generate mitotic checkpoint signaling when unattached, recruiting maximum levels of Mad2. Use of YFP-marked Mad1 reveals that throughout the mitotic delay some aligned, CENP-F depleted kinetochores continuously recruit Mad1. Others rebind YFP-Mad1 intermittently so as to produce 'twinkling', demonstrating cycles of mitotic checkpoint reactivation and silencing and a crucial role for CENP-F in efficient assembly of a stable microtubule-kinetochore interface.