X-ray Diffraction Analysis and Williamson-Hall Method in USDM Model for Estimating More Accurate Values of Stress-Strain of Unit Cell and Super Cells (2 × 2 × 2) of Hydroxyapatite,Confirmed by Ultrasonic Pulse-Echo Test

Taking into account X-ray diffraction, one of the well-known methods for calculating the stress-strain of crystals is Williamson-Hall (W–H). The W-H method has three models, namely (1) Uniform deformation model (UDM); (2) Uniform stress deformation model (USDM); and (3) Uniform deformation energy density model (UDEDM). The USDM and UDEDM models are directly related to the modulus of elasticity (E). Young’s modulus is a key parameter in engineering design and materials development. Young’s modulus is considered in USDM and UDEDM models, but in all previous studies, researchers used the average values of Young’s modulus or they calculated Young’s modulus only for a sharp peak of an XRD pattern or they extracted Young’s modulus from the literature. Therefore, these values are not representative of all peaks derived from X-ray diffraction; as a result, these values are not estimated with high accuracy. Nevertheless, in the current study, the W-H method is used considering the all diffracted planes of the unit cell and super cells (2 × 2 × 2) of Hydroxyapatite (HA), and a new method with the high accuracy of the W-H method in the USDM model is presented to calculate stress (σ) and strain (ε). The accounting for the planar density of atoms is the novelty of this work. Furthermore, the ultrasonic pulse-echo test is performed for the validation of the novelty assumptions.     

Somatic complaints and refrain from buying prescribed medications. Results from a cross-sectional study on people 60 years and older living in Kaunas (Lithuania)

Background

The use of medicines by elderly people is a growing area of concern in social pharmacy. A significant proportion of older people do not follow the recommendations from physicians and refrain from buying prescribed medications. The aim of this study is to evaluate associations between self-rated health, somatic complaints and refraining from buying prescribed medications by elderly people.

Findings

Data was collected in a cross-sectional study in 2009. We received 624 completed questionnaires (response rate – 48.9%) from persons aged 60–84 years living in Kaunas (Lithuania). Somatic complaints were measured with the 24 item version of the Giessen Complaint List (GBB-24). Logistic regression (Enter model) was used for evaluation of the associations between refraining from buying medications and somatic complaints. These associations were measured using odds ratio (OR) and calculating the 95% confidence interval (CI).The mean scores in total for the GBB scale and sub-scales (exhaustion, gastrointestinal and cardiovascular) were lowest among respondents who did not refrain from buying prescribed medications (means for GBB-24 scale: 21.04 vs. 24.82; p=0.001). Logistic regression suggests that somatic complaints were associated with a increased risk of refraining from buying prescribed medications (OR=1.35, 95% CI=1.15-1.60).

Conclusions

Somatic complaints were significantly associated with the decision to refrain from buying prescribed medications.     

Decreased lymphangiogenesis and lymph node metastasis by mTOR inhibition in head and neck cancer

Despite our improved understanding of cancer, the 5-year survival rate for head and neck squamous cell carcinomas (HNSCC) patients remains relatively unchanged at 50% for the past three decades. HNSCCs often metastasize to locoregional lymph nodes, and lymph node involvement represents one of the most important prognostic factors of poor clinical outcome. Among the multiple dysregulated molecular mechanism in HNSCCs, emerging basic, preclinical, and clinical findings support the importance of the mTOR signaling route in HNSCC progression. Indeed, we observed here that the activation of mTOR is a widespread event in clinical specimens of HNSCCs invading locoregional lymph nodes. We developed an orthotopic model of HNSCC consisting of the implantation of HNSCC cells into the tongues of immunocompromised mice. These orthotopic tumors spontaneously metastasize to the cervical lymph nodes, where the presence of HNSCC cells can be revealed by histologic and immunohistochemical evaluation. Both primary and metastatic experimental HNSCC lesions exhibited elevated mTOR activity. The ability to monitor and quantitate lymph node invasion in this model system enabled us to explore whether the blockade of mTOR could impact HNSCC metastasis. We found that inhibition of mTOR with rapamycin and the rapalog RAD001 diminished lymphangiogenesis in the primary tumors and prevented the dissemination of HNSCC cancer cells to the cervical lymph nodes, thereby prolonging animal survival. These findings may provide a rationale for the future clinical evaluation of mTOR inhibitors, including rapamycin and its analogues, as part of a molecular-targeted metastasis preventive strategy for the treatment of patients with HNSCC.     

A case of almagel-induced methemoglobinemia after pancreatoduodenal resection

We are reporting the case of severe methemoglobinemia resulting from Almagel which was given for treatment of gastrointestinal ulcers after pancreatoduodenal resection. A 64 year old man was treated with Almagel A postoperatively. One day after treatment began, the patient reported what appeared to be cyanotic discolorations of his lips and fingers. (SpO₂ 80%, normal pO₂). Two days later, the patient was diagnosed with methemoglobinemia via co-oximetry and treated with methylene blue. The causes of methemoglobinemia remained unclear, and Almagel A was reinitiated until the second episode of methemoglobinemia, was diagnosed and treated promptly. The dose of benzocaine in Almagel A (100 mg/5 ml) was sufficient enough to cause methemoglobinemia, confirmed using multiwavelength co-oximeter and successfully treated with methylene blue.     

A Novel Function of p53: A Gatekeeper of Retinal Detachment

Proliferative vitreoretinopathy (PVR) is a blinding disease associated with rhegmatogenous retinal detachment, for which there is no satisfactory treatment. Surgery helps in many cases, but, to our knowledge, there are no pharmacological approaches to reduce PVR risk. We report that suppressing expression of p53 was a required event in two assays of PVR (namely, platelet-derived growth factor receptor α-mediated contraction of cells in a collagen gel and retinal detachment in an animal model of PVR). Furthermore, preventing the decline in the level of p53 with agents such as Nutlin-3 protected from retinal detachment, which is the most vision-compromising component of PVR. Finally, Nutlin-3 may be effective in the clinical setting because it prevented human PVR vitreous-induced contraction of cells isolated from a patient PVR membrane. These studies identify Nutlin-3 as a potential PVR prophylaxis.     

Increasing the success rate of lantibiotic drug discovery by Synthetic Biology

INTRODUCTION: Lantibiotics are post-translationally modified antimicrobial peptides produced by bacteria from diverse environments that exhibit an activity against pathogenic bacteria comparable to that of medically used antibiotics. The actual need for new antimicrobials in therapeutics has placed them in the pipeline of antibiotic research, due not only to their high antimicrobial activity but also to the fact that they are directed to novel targets. AREAS COVERED: This review covers the different approaches traditionally used in bacteriocin discovery, based on the isolation of bacteria from different habitats and determining their inhibitory spectrum against a set of relevant strains. It also elaborates on more recent approaches covering organic synthesis and semi-synthesis of lantibiotics, genomic and proteomic approaches and the application of Synthetic Biology to the field of antimicrobial drug discovery. EXPERT OPINION: Lantibiotics show a great potential in fulfilling the requirements for new antimicrobials. Culture-dependent techniques are still applied to lantibiotic discovery producing successful results that can be furthered by employing high-throughput screening techniques and peptidogenomics. The necessity of culturing bacteria and growing them in specific conditions for lantibiotic expression, can hamper the discovery rate, especially in exotic or unculturable bacteria. Thus, a combination of genome mining procedures, to detect novel lantibiotic-related sequences, with heterologous production systems and high-throughput screening, offers a promising strategy. Furthermore, the characterization of the mechanism of action of many lantibiotics, and the development of "plug and play" peptide biosynthesis systems, offers the possibility of initiating the rational design of non-natural lantibiotics based on structure-activity relationships.