Role of nanotechnology in the prolonged release of drugs by the subcutaneous route.

INTRODUCTION: Subcutaneous physiology is distinct from other parenteral routes that benefit the administration of prolonged-release formulations. A prolonged-release effect is particularly convenient for treating chronic diseases because it is associated with complex and often prolonged posologies. Therefore, drug-delivery systems focused on nanotechnology are proposed as alternatives that can overcome the limitations of current therapeutic regimens and improve therapeutic efficacy. AREAS COVERED: This review presents an updated systematization of nanosystems, focusing on their applications in highly prevalent chronic diseases. Subcutaneous-delivered nanosystem-based therapies comprehensively summarize nanosystems, drugs, and diseases and their advantages, limitations, and strategies to increase their translation into clinical applications. An outline of the potential contribution of quality-by-design (QbD) and artificial intelligence (AI) to the pharmaceutical development of nanosystems is presented. EXPERT OPINION: Although recent academic research and development (R&D) advances in the subcutaneous delivery of nanosystems have exhibited promising results, pharmaceutical industries and regulatory agencies need to catch up. The lack of standardized methodologies for analyzing in vitro data from nanosystems for subcutaneous administration and subsequent in vivo correlation limits their access to clinical trials. There is an urgent need for regulatory agencies to develop methods that faithfully mimic subcutaneous administration and specific guidelines for evaluating nanosystems.

Media use, dietary intake, and diet quality of adolescents in Saudi Arabia.

BACKGROUND: Excessive media use can affect diet of adolescents, but relevant data in Saudi Arabia are lacking. The present study aimed to explore the association between media use, dietary intake, and diet quality among adolescents. METHODS: This cross-sectional study included data of 631 adolescents (ages 11-18 years) who were randomly recruited from 16 schools located in two main cities in the Western region of Saudi Arabia (Madinah and Jeddah). Envelopes including a questionnaire were sent home to collect sociodemographic data. Students then completed the short-form food frequency questionnaire to assess diet quality. Data on media use, anthropometrics, and 24-h dietary recalls were also collected. RESULTS: A high proportion of adolescents (86.2%) exceeded media use recommendations of ≤2 h per day. Significantly higher proportions of younger adolescents, males, and non-Saudis reported media use within the recommendation compared to their peers. Media use predicted lower diet quality score (B = -0.67 [95% CI: -1.09 to -0.28]) and lower intake of calcium, zinc, vitamin D, and vitamin C (B = -104 [95% CI: -203 to -5.24], B = -2.13 [95% CI: -4.15 to -0.11], B = -23.5 [95% CI: -41.3 to -5.65], B = -24.0 [95% CI: -45.1 to -2.96], respectively). CONCLUSION: Interventions to limit media use are urgently needed for adolescents in Saudi Arabia to improve diet quality and overall nutritional health. IMPACT: Excessive media use can affect diet of adolescents, but relevant data are lacking in Saudi Arabia. The majority of adolescents exceed the recommendations for media use. Media use was negatively associated with diet quality and intake of calcium, zinc, vitamin D, and vitamin C. This study will inform public health entities and policy makers to draw evidence-based, culturally tailored recommendations and develop nutrition interventions to enhance diet quality and nutritional status of adolescents. Findings of this study highlight the urgency to develop intervention programs and policies that aim to limit media use among adolescents.

Phenotypic and genotypic detection of carbapenemase production among gram negative bacteria isolated from hospital acquired infections.

OBJECTIVES: To identify the carbapenemase producing Gram-negative bacteria (GNB) by phenotypic methods and to confirm the presence of resistant genes using real-time polymerase chain reaction (PCR). METHODS: This was a prospective study carried out at the Department of Microbiology, Sri Venkata Sai Medical College and Hospital, Mahabubnagar, India, from March 2018-2021. All samples were screened for carbapenem resistance by disc diffusion method and the VITEK®2 compact system (bioMérieux, France). Detection of carbapenemase was carried out using RAPIDEC®CARBA NP test (Biomeriux Private Limited, South Delhi, India), screening for metallo-ß-lactamases (MBL) was carried out by double disk synergy test (DDST), and genotypic characterization by real-time PCR. RESULTS: Among the 1093 Gram-negative bacilli identified, 220 (17.0%) were resistant to carbapenems by both tested methods. Carbapenemase detection using the RAPIDEC®CARBA NP test indicated that 207 (94.0%) were carbapenemase producers, of which 189 (91.2%) were MBL producers. The most common carbapenemase genes identified were New Delhi metallo-ß-lactamase (NDM; 47.3%), followed by the co-existence of genes in combination of NDM, with Verona integron-mediated metallo-ß-lactamase (VIM; 39.6%), VIM and oxacillin hydrolyzing enzymes-48 (OXA-48; 4.3%), and OXA-48 (1.4%).No gene of active on imipenem, Klebsiella pneumonia carbapenemase, VIM, or OXA-48 alone was detected. CONCLUSION: This study suggests routine carbapenem resistance testing among multi-drug resistant-GNBs, as most of these infections occur in hospitals. In addition, there is a possibility that these highly antibiotic-resistant genes could spread to other bacteria resulting in further dissemination.

Effect of CAD-CAM tool deterioration on the trueness of ceramic restorations.

STATEMENT OF PROBLEM: Tools will gradually deteriorate with repetitive milling. However, tool lifetime can vary depending on the type of milling machine, the hardness of the ceramic material, and the size of the restoration. Studies evaluating the effect of tool deterioration on the trueness of milled restorations are lacking. PURPOSE: The purpose of this study was to evaluate the effect of tool deterioration on the trueness of milled restorations. MATERIAL AND METHODS: A patient requiring a ceramic crown was recruited. Repetitive milling of zirconia crowns (inCoris TZI; Dentsply Sirona) with tungsten carbide rotary instruments and glass-ceramic crowns (VITABLOCS mark II; Vita Zahnfabrik) with diamond rotary instruments was performed by using a 5-axis milling machine (inLab MC X5; Dentsply Sirona) until the machine software program indicated replacing the largest tool. The percentage of deterioration for the largest tool was recorded before each milling. The trueness for different crown areas was evaluated by using a 3-dimensional evaluation software program (Geomagic Control X; 3D systems), and the crowns were clinically evaluated. The crowns were grouped into 4 quadrants as per the deterioration percentage. The Pearson correlation (r) between the deterioration percentage and trueness and linear contrast analysis (partial eta squared [η]) among the groups were performed. RESULTS: Glass-ceramic crown areas had low correlation except for mesial (high, r=0.63, high, η=0.37) and distal (medium, r=0.42, high, η= 0.34) areas, whereas zirconia crowns had low correlation for inner and internal areas and medium to high correlation for mesial (r= -0.31, η=0.33), distal (r= -0.53, η=0.36), occlusal (r= -0.32, η=0.164), external (r= 0.69, η=0.52), and marginal (r= -0.44, η=0.19) areas. Zirconia crowns had excellent marginal fit and occlusal contact and light to excellent proximal contact, whereas glass-ceramic crowns had excellent marginal fit, minor to major occlusal correction, and heavy proximal contact. CONCLUSIONS: The effect of tool deterioration on trueness depended on material type and crown area. Only proximal areas were affected in the glass-ceramic crowns, whereas external, proximal, occlusal, and marginal areas were affected in the zirconia crowns. Trueness did not necessarily reflect the clinical quality of the crown, as both crown types were clinically satisfactory. Although zirconia crowns were overmilled in comparison with the reference design and glass-ceramic crowns, they had better clinical quality.

Quality of Life in Hematologic Malignancy in the Eastern Mediterranean Region: A Systematic Review.

Health-related quality of life (HRQoL) indicates patients' overall health and is an essential aspect of cancer care. Although multiple studies have addressed the various aspects of HRQoL in cancer patients, few studies have investigated HRQoL in hematologic malignancy patients in the Eastern Mediterranean region (EMR). This review conducted an electronic search using OVID-Medline to identify HRQoL-related articles involving hematologic malignancy patients in the EMR. Eight studies met the inclusion criteria. Two studies validated translated QoL psychometric instruments, three were observational studies, and three were interventional studies. Except for the validation studies, all studies discussed HRQoL in leukemia patients. Our review highlighted a scarcity in the number of studies focusing on patients with hematological malignancies in this region. The included studies demonstrated the negative impact of hematological malignancies and therapies on patients' HRQoL. In addition, the studies displayed the association between physical symptoms and QoL of cancer patients, necessitating the importance of addressing these symptoms. The studies were limited by publication year, the number of patients, geographical locations, and disease entities. Future studies in this area are encouraged to help understand factors affecting HRQoL in the EMR region and ways to improve it. Consequently, further research is needed to establish translated and validated QoL assessment instruments that target patients in the EMR using the most common tools including the Short-Form 36-item Health Survey and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire.

Effect of Milling Protocols on Trueness and Precision of Ceramic Crowns.

PURPOSE: To investigate the effect of different milling protocols for different ceramic materials on the trueness and precision of milled ceramic crowns. MATERIALS AND METHODS: A definitive impression from a patient requiring a ceramic crown was used to fabricate forty glass ceramic crowns (VITABLOCS mark II, Vita Zahnfabrik) milled with wet, hard milling protocol, and 40 zirconia crowns (inCoris TZI, Dentsply, Sirona) milled with dry, soft milling protocol, using a 5-axis milling machine (inLab MC X5; Dentsply Sirona). Trueness and precision for different crown areas were evaluated with a 3D evaluation software (Geomagic Control X, 3D systems). Statistical analysis was performed between the 2 crown types with independent t-test, and analysis of variances followed by Bonferroni tests among crown areas for each crown. RESULTS: All areas of the glass ceramic crowns had higher trueness than the zirconia crown areas (p < 0.05). Crown areas of each crown type had significantly different trueness values (p < 0.001, F = 175.17 for glass crowns, p < 0.001, F = 35.04 for zirconia crowns). Glass crowns had 3.78 µm precision, while zirconia crowns had 4.12 µm precision, with a precision difference range between the 2 types of crowns from 0.32 µm for the inner surface to 6.5 µm for the marginal surface. CONCLUSIONS: Type of ceramic material and milling protocol affected trueness of the milled crown, with higher trueness for the hardmilled glass crowns than the soft milled zirconia crowns. Soft milled zirconia crowns were generally overmilled in comparison with the reference design and glass crowns. However, glass crowns exhibited more undermilling in thin and deep areas. The crown area affected trueness, with external areas having better trueness than internal areas. The 5-axis milling machine had high precision, which was minimally affected by the ceramic type, milling protocol, or crown area.

Wave propagation analysis in spiral geometries.

In this paper wave propagation in strings of exponential and conical spiral geometries and in an exponential spiral horn of increasing circular cross-section area is studied. The three-dimensional wave equation in cylindrical coordinates is investigated, as the theoretical solution in the exponential spiral horn is derived and in the case of the strings, numerical simulation mainly using a centered in time and space finite difference scheme is carried out. The results suggest non-harmonic resonance modes in both of the conical and exponential spiral strings.

Bio-conjugation of antioxidant peptide on surface-modified gold nanoparticles: a novel approach to enhance the radical scavenging property in cancer cell.

BACKGROUND: Functionalized gold nanoparticles are emerging as a promising nanocarrier for target specific delivery of the therapeutic molecules in a cancer cell, as a result it targeted selectively to the cancer cell and minimized the off-target effect. The functionalized nanomaterial (bio conjugate) brings novel functional properties, for example, the high payload of anticancer, antioxidant molecules and selective targeting of the cancer molecular markers. The current study reported the synthesis of multifunctional bioconjugate (GNPs-Pep-A) to target the cancer cell. METHODS: The GNPs-Pep-A conjugate was prepared by functionalization of GNPs with peptide-A (Pro-His-Cys-Lys-Arg-Met; Pep-A) using thioctic acid as a linker molecule. The GNPs-Pep-A was characterized and functional efficacy was tested using Retinoblastoma (RB) cancer model in vitro. RESULTS: The GNPs-Pep-A target the reactive oxygen species (ROS) in RB, Y79, cancer cell more effectively, and bring down the ROS up to 70 % relative to control (untreated cells) in vitro. On the other hand, Pep-A and GNPs showed 40 and 9 % reductions in ROS, respectively, compared to control. The effectiveness of bioconjugate indicates the synergistic effect, due to the coexistence of both organic (Pep-A) and inorganic phase (GNPs) in novel GNPs-Pep-A functional material. In addition to this, it modulates the mRNA expression of antioxidant genes glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT) by two-threefolds as observed. CONCLUSIONS: The effects of GNPs-Pep-A on ROS reduction and regulation of antioxidant genes confirmed that Vitis vinifera L. polyphenol-coated GNPs synergistically improve the radical scavenging properties and enhanced the apoptosis of cancer cell.

Optimization of flow assisted entrapment of pollen grains in a microfluidic platform for tip growth analysis.

A biocompatible polydimethylsiloxane (PDMS) biomicrofluidic platform is designed, fabricated and tested to study protuberance growth of single plant cells in a micro-vitro environment. The design consists of an inlet to introduce the cell suspension into the chip, three outlets to conduct the medium or cells out of the chip, a main distribution chamber and eight microchannels connected to the main chamber to guide the growth of tip growing plant cells. The test cells used here were pollen grains which produce cylindrical protrusions called pollen tubes. The goal was to adjust the design of the microfluidic network with the aim to enhance the uniformly distributed positioning of pollen grains at the entrances of the microchannels and to provide identical fluid flow conditions for growing pollen tubes along each microchannel. Computational fluid analysis and experimental testing were carried out to estimate the trapping efficiencies of the different designs.

An approach to chemotherapy-associated toxicity.

The effects of chemotherapy in multiple organ systems may be challenging to discern from the sequelae of malignancy and systemic illnesses with concomitant immunocompromise. Chemotherapeutic agents typically affect multiple organ systems. Intrathecal medication errors may pose particularly devastating neurologic consequences and death, often requiring emergent intervention. This article provides an overview of commonly used chemotherapeutic drugs, indications for use, their adverse effects by organ system, and the management of commonly encountered toxicities. Intrathecal medication errors and specific antidotes are discussed in pertinent management sections. Emergency department management should focus on rapid patient assessment, immediate intervention following intrathecal medication errors, exclusion of infection, and excellent supportive care.

Occupational health characteristics of women on dairy farms in Pennsylvania.

Women play a significant role in Pennsylvania production agriculture, thereby exposing themselves to occupational health risks. The goal of this cross-sectional study was to assess the incidence of health conditions with a possible zoonotic origin in this underserved population. A written survey was sent to a stratified, random sample of dairy farms in Pennsylvania (n = 3709) using a modified version of the Dillman method. In addition to demographic data, the survey was used to collect information on the occurrence of zoonotic diseases, gastrointestinal illnesses, respiratory problems, dermatoses, and women's reproductive health issues. Of the 624 respondents, 10.4% (n = 65) reported that they had contracted a disease from an animal. Interestingly, only 9 respondents indicated that they had suffered from foodborne illnesses in the past year including salmonellosis (n = 1), campylobacteriosis (n = 1), and gastroenteritis due to Escherichia coli (n = 1). A risk factor associated with difficulty breathing was the lack of use of a breathing mask, whereas ventilation in the free stall area appeared to offer a protective effect. Difficulty breathing was reported by 9.8% (n = 61) of the respondents. Risk factors associated with skin disorders included raising fruits and/or vegetables, raising swine, and not wearing gloves when milking. The findings of the study suggest that many of the illnesses and conditions could have been acquired by working with dairy animals and their environment. Based on the findings of this study, additional investigations on the causes and prevention of these illnesses are warranted.

Occupational health behaviors and habits of women on dairy farms in Pennsylvania.

The goal of this study was to determine what tasks women perform, behaviors that could result in exposure to zoonotic disease, and preventative measures practiced by women on dairy farms. A written survey was sent to a stratified, random sample of dairy farms in Pennsylvania (n = 3709) using a modified version of the Dillman method. The tasks most commonly performed by the respondents (n = 624) included milking (70.8%), feeding (60.6%), and cleaning stalls (42.6%). The use of personal protective equipment was infrequent. Gloves were always worn when milking by 32.7%. More respondents, 96.5%, changed their clothes at least sometimes before working in the barn as compared to when leaving the barn. Handwashing was always performed by 86.7% after assisting with delivering calves, whereas 71.1% always washed their hands after milking. Eating and drinking in the barn were practiced by 45.0% and 72.0%, respectively. Veterinary obstetric drugs were administered by 28.2% of the respondents. Most of the respondents, 89.7%, indicated that they felt they had minimal to no risk of contracting a disease from the animals with which they worked.

Characterization of thick and thin film SiCN for pressure sensing at high temperatures.

Pressure measurement in high temperature environments is important in many applications to provide valuable information for performance studies. Information on pressure patterns is highly desirable for improving performance, condition monitoring and accurate prediction of the remaining life of systems that operate in extremely high temperature environments, such as gas turbine engines. A number of technologies have been recently investigated, however these technologies target specific applications and they are limited by the maximum operating temperature. Thick and thin films of SiCN can withstand high temperatures. SiCN is a polymer-derived ceramic with liquid phase polymer as its starting material. This provides the advantage that it can be molded to any shape. CERASET™ also yields itself for photolithography, with the addition of photo initiator 2, 2-Dimethoxy-2-phenyl-acetophenone (DMPA), thereby enabling photolithographical patterning of the pre-ceramic polymer using UV lithography. SiCN fabrication includes thermosetting, crosslinking and pyrolysis. The technology is still under investigation for stability and improved performance. This work presents the preparation of SiCN films to be used as the body of a sensor for pressure measurements in high temperature environments. The sensor employs the phenomenon of drag effect. The pressure sensor consists of a slender sensitive element and a thick blocking element. The dimensions and thickness of the films depend on the intended application of the sensors. Fabrication methods of SiCN ceramics both as thin (about 40-60 µm) and thick (about 2-3 mm) films for high temperature applications are discussed. In addition, the influence of thermosetting and annealing processes on mechanical properties is investigated.

Penetration-enhancing effect of ethanolic solution of menthol on transdermal permeation of ondansetron hydrochloride across rat epidermis.

The aim of this investigation was to study the effect of an ethanol-water solvent system and ehtanolic solution of menthol on the permeation of ondansetron hydrochloride across the rat epidermis in order to select a suitable ethanol-water vehicle and optimal concentration of menthol for the development of a transdermal therapeutic system. The solubility of ondansetron hydrochloride in ethanol, water and selected concenetrtaion of ethanol-water vehicles (20:80 v/v, 40:60 v/v and 60:40 v/v) was determined. The effect of these solvent vehicles, containing 1.5% w/v of ondansetron hydrochloride, on the in vitro permeation of the drug was studied across the rat epidermis. The highest permeation was observed from 60% v/v of ethanol-water vehicle that showed highest solubilty. Hence, the hydroxypropyl cellulose (HPC) (2% w/w) gel formulations containing 1.5% w/w of ondansetron hydrochloride and selected concentrations of menthol (0, 2, 4, 8 and 10% w/w) were prepared using 60% v/v of ethanol-water vehicle, and subjected to in vitro permeation of the drug across rat epidermis. The transdermal permeation of ondansetron hydrochloride was enhanced markedly by the addition of menthol to HPC gel drug reservoir formulations. A maximum flux of ondansetron hydrochloride (77.85 +/- 2.85 mu g/cm(2.)h) was observed with a mean enhancement ratio of 13.06 when menthol was incorporated at a concentration of 8% w/w in HPC gels. However, there was no significant increase in the drug flux with 10% w/w menthol when compared to that obtained with 8% w/w of menthol in HPC gel formulations. The results suggest that 2% w/w HPC gel drug reservoir formulation, prepared with 60% v/v ethanol-water, containing 8% w/w of menthol provides an optimal transdermal permeation of ondansetron hydrochloride.

Cellular and reticular variants of haemangioblastoma revisited: a clinicopathologic study of 88 cases.

The presence of histological variants of haemangioblastoma is well established, but data on the prognostic implications of histological subtyping are missing. We thus characterized clinical factors associated with histological subtypes, that is, of the cellular and reticular variant of haemangioblastoma, in a series of 88 consecutive primary haemangioblastomas of the central nervous system. Ten haemangioblastomas were classified as 'cellular' according to Cushing and Bailey. As compared to the more common 'reticular' variant (n = 78), the proportion of tumours containing glial fibrillary acidic protein-positive tumour cells (80% vs. 7%), as well as median Ki67 (MIB1) proliferation indices [4% (quartiles: 1-8%) vs. < 1% (<1-2%)], was significantly higher in cellular haemangioblastomas (P < 0.01). Recurrences were more frequent in the cellular variant [2/8 (25%) vs. 4/51 (8%)]. Kaplan-Meier analysis confirmed a significantly higher probability of recurrence in the cellular variant (Log-Rank test P < 0.01). Cox regression analysis not only confirmed the well established association of von Hippel-Lindau disease with tumour recurrence (P < 0.01), but also revealed an independent effect of histological subtype on the probability of recurrence (P < 0.05), whereas no significant influence of age, sex or tumour location was observed. To conclude, the results from this retrospective study suggest that histological subtyping of haemangioblastomas has prognostic implications and might contribute to identify patients at risk for recurrence.

In vivo evaluation of limonene-based transdermal therapeutic system of nicorandil in healthy human volunteers.

Hydroxypropyl methylcellulose (HPMC) gel drug reservoir system prepared with 70:30 v/v ethanol-water solvent system containing 6% w/w of limonene was effective in promoting the in vitro transdermal delivery of nicorandil. The objective of the present study was to fabricate and evaluate a limonene-based transdermal therapeutic system (TTS) for its ability to provide the desired steady-state plasma concentration of nicorandil in human volunteers. The in vitro permeation of nicorandil from a limonene-based HPMC gel drug reservoir was studied across excised rat skin (control), EVA2825 membrane, adhesive-coated EVA2825 membrane and adhesive-coated EVA2825 membrane-excised rat skin composite to account for their effect on the desired flux of nicorandil. The flux of nicorandil from the limonene-based HMPC drug reservoir across EVA2825 membrane decreased to 215.8 +/- 9.7 microg/cm(2).h when compared to that obtained from control, indicating that EVA2825 was effective as a rate-controlling membrane. The further decrease in nicorandil flux across adhesive-coated EVA2825 membrane and adhesive-coated EVA2825 membrane-excised rat skin composite showed that the adhesive coat and skin also controlled the in vitro transdermal delivery. The limonene-based drug reservoir was sandwiched between adhesive-coated EVA2825-release liner composite and a backing membrane. The resultant sandwich was heat-sealed as circle-shaped patch (20 cm(2)), trimmed and subjected to in vivo evaluation in human volunteers against immediate-release tablets of nicorandil (reference formulation). The fabricated limonene-based TTS of nicorandil provided a steady-state plasma concentration of 21.3 ng/ml up to 24 h in healthy human volunteers. It was concluded that the limonene-based TTS of nicorandil provided the desired plasma concentration of the drug for the predetermined period of time with minimal fluctuations and improved bioavailability.