Quantum Dots for Biological Applications

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Microfluidics based manufacture of liposomes simultaneously entrapping hydrophilic and lipophilic drugs

Despite the substantial body of research investigating the use of liposomes, niosomes and other bilayer vesicles for drug delivery, the translation of these systems into licensed products remains limited. Indeed, recent shortages in the supply of liposomal products demonstrate the need for new scalable production methods for liposomes. Therefore, the aim of our research has been to consider the application of microfluidics in the manufacture of liposomes containing either or both a water soluble and a lipid soluble drug to promote co-delivery of drugs. For the first time, we demonstrate the entrapment of a hydrophilic and a lipophilic drug (metformin and glipizide respectively) both individually, and in combination, using a scalable microfluidics manufacturing system. In terms of the operating parameters, the choice of solvents, lipid concentration and aqueous:solvent ratio all impact on liposome size with vesicle diameter ranging from ∼90 to 300 nm. In terms of drug loading, microfluidics production promoted high loading within ∼100 nm vesicles for both the water soluble drug (20–25% of initial amount added) and the bilayer embedded drug (40–42% of initial amount added) with co-loading of the drugs making no impact on entrapment efficacy. However, co-loading of glipizide and metformin within the same liposome formulation did impact on the drug release profiles; in both instances the presence of both drugs in the one formulation promoted faster (up to 2 fold) release compared to liposomes containing a single drug alone. Overall, these results demonstrate the application of microfluidics to prepare liposomal systems incorporating either or both an aqueous soluble drug and a bilayer loaded drug

Serum Lactate Dehydrogenase Level in Acute Leukemias

Background: Acute leukemias are clonal neoplastic proliferations of immature cells of the hemopoietic system. They are divided into acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and acute undifferentiated leukemia (AUL). LDH has been suggested as a possible non-specific tumor marker for many years, and total serum LDH is frequently elevated in neoplastic diseases. The aims of the study are to evaluate the significance of increased serum LDH levels in patients with acute leukemia and to determine the importance of serum LDH level in the follow up and assessment of treatment responses. Patients, Materials and Methods: This study was conducted at Baghdad Teaching Hospital in Medical City during the period of October 2003 till October 2004. It included 108 patients with acute leukemias. The patient groups were compared with 21 apparently healthy control subjects. All patients had full medical history, complete physical examination, and routine investigations and other specific investigations e.g. BM aspiration and biopsy. Serum lactate dehydrogenase LDH level was estimated in all patients serially during diagnosis and after chemotherapy as well as in control subjects. Results: Total serum LDH levels were significantly higher among patients with acute leukemias compared to that of the controls. Comparing the three types of leukemic patients, no  significant difference was observed in total serum LDH levels between AML, ALL and AUL patients. Regarding treatment, levels of total serum LDH were significantly decreased in both remitter and non-remitter patients with acute leukemia with no significant difference between them. Conclusion: Although total serum LDH is higher in all acute leukemic patients, it is hardly discriminator between subsets of acute leukemia and is of little value in the prognosis and prediction of treatment response and outcome

SMAD4 - Molecular gladiator of the TGF-β signaling is trampled upon by mutational insufficiency in colorectal carcinoma of Kashmiri population: an analysis with relation to KRAS proto-oncogene

<p>Abstract</p> <p>Background</p> <p>The development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the <it>SMAD4 </it>gene mutations with <it>KRAS </it>mutant status has not been explored by many studies so far. Here, in this study we aimed to investigate the role of <it>SMAD4 </it>gene aberrations in the pathogenesis of CRC in Kashmir valley and to correlate it with various clinicopathological variables and <it>KRAS </it>mutant genotype.</p> <p>Methods</p> <p>We examined the paired tumor and normal tissue specimens of 86 CRC patients for the occurrence of aberrations in MCR region of <it>SMAD4 </it>and exon 1 of <it>KRAS </it>by PCR-SSCP and/or PCR-Direct sequencing.</p> <p>Results</p> <p>The overall mutation rate of mutation cluster region (MCR) region of <it>SMAD4 </it>gene among 86 patients was 18.6% (16 of 86). 68.75% (11/16) of the <it>SMAD4 </it>gene mutants were found to have mutations in <it>KRAS </it>gene as well. The association between the <it>KRAS </it>mutant genotype with <it>SMAD4 </it>mutants was found to be significant (P =< 0.05). Further more, we found a significant association of tumor location, tumor grade, node status, occupational exposure to pesticides and bleeding PR/Constipation with the mutation status of the <it>SMAD4 </it>gene (P =< 0.05).</p> <p>Conclusion</p> <p>Our study suggests that <it>SMAD4 </it>gene aberrations are the common event in CRC development but play a differential role in the progression of CRC in higher tumor grade (C+D) and its association with the <it>KRAS </it>mutant status suggest that these two molecules together are responsible for the progression of the tumor to higher/advanced stage.</p

Exposure to secondary traumatic stress and its related factors among emergency nurses in Saudi Arabia: a mixed method study

Background: Emergency department (ED) nurses are exposed to the risk of secondary traumatic stress (STS), which poses a threat not only to nurses’ health and psychological well-being but also adversely affects the execution of their professional duties. The quality and outcome of their nursing services are negatively affected by STS. Purpose: The purpose of this study is to comprehensively investigate the prevalence and intensity of Secondary Traumatic Stress (STS) among Emergency Department (ED) nurses. It aims to identify and analyze the socio-demographic, occupational, and psychological factors that influence the severity and variation of STS experienced by these nurses. Methods: The study utilized a sequential explanatory mixed methods approach, including two phases. Phase 1 employed a cross-sectional study design, utilizing a convenience sample of 181 nurses to explore the levels of STS and the factors associated with it. Following this, Phase 2 was structured as a qualitative descriptive study, which involved conducting semi-structured interviews with a purposefully selected group of ten ED nurses. Data collection took place at three major hospitals in Saudi Arabia during the period from January to June 2022. Results: A total of 181 participants were included in the study. The mean STSS score reported by the nurses was 51 (SD = 13.23) out of the maximum possible score of 85, indicating severe STS among ED nurses. Factors associated with an increase in the levels of STS among ED nurses included being female, older in age, married, possessing higher education and experience, having a positive relationship with colleagues, receiving organisational support, and dealing with a higher number of trauma cases. Several themes emerged from the qualitative interviews including: ED Characteristics: Dual Impact on STS, Emotional Resonance and Vulnerability, Personal Life Stressors, The Ability to Cope, and Social Support. Conclusion and implications for practice: Future strategies and interventions targeting STS should be prioritized to effectively manage its impact on ED nurses. It is crucial to develop targeted interventions that address the specific factors contributing to STS, as identified in this study. Additionally, these findings aim to enhance awareness among nursing administrators, managers, and supervisors about the critical factors associated with STS. This awareness is essential for accurately assessing and developing interventions that mitigate STS among nursing staff

Bladder Sparing Approaches for Muscle-Invasive Bladder Cancers.

OPINION STATEMENT: Organ preservation has been increasingly utilised in the management of muscle-invasive bladder cancer. Multiple bladder preservation options exist, although the approach of maximal TURBT performed along with chemoradiation is the most favoured. Phase III trials have shown superiority of chemoradiotherapy compared to radiotherapy alone. Concurrent chemoradiotherapy gives local control outcomes comparable to those of radical surgery, but seemingly more superior when considering quality of life. Bladder-preserving techniques represent an alternative for patients who are unfit for cystectomy or decline major surgical intervention; however, these patients will need lifelong rigorous surveillance. It is important to emphasise to the patients opting for organ preservation the need for lifelong bladder surveillance as risk of recurrence remains even years after radical chemoradiotherapy treatment. No randomised control trials have yet directly compared radical cystectomy with bladder-preserving chemoradiation, leaving the age-old question of superiority of one modality over another unanswered. Radical cystectomy and chemoradiation, however, must be seen as complimentary treatments rather than competing treatments. Meticulous patient selection is vital in treatment modality selection with the success of recent trials within the field of bladder preservation only being possible through this application of meticulous selection criteria compared to previous decades. A multidisciplinary approach with radiation oncologists, medical oncologists, and urologists is needed to closely monitor patients who undergo bladder preservation in order to optimise outcomes

Role of Nemolizumab and Omalizumab in management of atopic dermatitis: A review

BackgroundNemolizumab (CIM331) is a monoclonal antibody that binds the IL-31 receptor α component. This inhibits IL-31 from acting on neurons that constrains the initialization of the sense of pruritus in cases of atopic dermatitis.AimsTo summarize the results of reported studies evaluating the role of nemolizumab and omalizumab in management of atopic dermatitis.Methods This is a systematic review was carried out, including PubMed, Google Scholar, and EBSCO that examining randomized controlled trials, observational, and experimental studies which study role of nemolizumab in management of atopic dermatitis.Results The review included 8 randomized studies reported efficacy of both nemolizumab and omalizumab for management of atopic dermatitis.ConclusionOther studies with large numbers of patients with AD are necessary to define the adverse effects of both drugs in the treatment of AD