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Introduction: This study aimed to gain insight from patients with refractoryMycobacterium aviumcomplex lung disease (MAC-LD) into strategies used to manage adverse events (AEs) associated with amikacin liposome inhalation suspension (ALIS). Methods: We conducted semi-structured interviews with US patients with refractory MAC-LD prescribed ALIS in a real-world setting. Interview transcripts were analyzed and coded to identify patterns in participants’ descriptions of their ALIS treatment experiences, including AEs and their disruptiveness, and AE mitigation strategies, including participants’ ratings of strategies’ effectiveness. Concept saturation was also assessed. Results: Twenty participants (mean age 48.7 years; 80% women; mean ALIS duration 5.45 months) were interviewed. At the time of the interview, 15 participants (75%) had received ALIS for > 1 month and 13 (65%) were currently receiving ALIS. Participants described 44 unique AE mitigation strategies, which can be categorized into three groups: prepare for treatment; prevent increased emergence of AEs; and persist on treatment by mitigating AEs. Common strategies (reported by ≥ 50% of participants) included use of educational materials from the patient support program, localized management of throat irritation, and symptom management to reduce fatigue. Evidence of concept saturation was observed: no new strategies were identified in the last five interviews, which suggests the sample was robust enough to identify all mitigation strategies likely to be used by the broader patient population. Conclusions: This real-world study identified a diverse set of potential AE mitigation strategies intended to help individual patients prepare for ALIS treatment, prevent the increased emergence of certain AEs, and mitigate the impact of AEs on treatment persistence. Developing a comprehensive accounting of the types of mitigation strategies in use among patients in real-world settings can inform future investigation of the effectiveness of such strategies, and support evidence-based recommendations for treatment management.

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Magnetic skyrmions are localized, stable topological magnetic textures that can move and interact with each other like ordinary particles when an external stimulus is applied. The efficient control of the motion of spin textures using spin-polarized currents opened an opportunity for skyrmionic devices such as racetrack memory and neuromorphic or reservoir computing. The coexistence of skyrmions with high topological charge in the same system promises further possibilities for efficient technological applications. In this work, we directly observe dipolar skyrmions and antiskyrmions with arbitrary topological charge in Co/Ni multilayers at room temperature. We explore the dipolar-stabilized spin objects with topological charges of up to 10 and characterize their nucleation process, their energy dependence on the topological charge and the effect of the material parameters on their stability. Furthermore, our micromagnetic simulations demonstrate spin-transfer-induced motion of these spin objects, which is important for their potential device application.

Synthetic antiferromagnets with perpendicular magnetic anisotropy (PMA-SAFs) have gained growing attention for both conventional and next-generation spin-based technologies. While the progress of PMA-SAF spintronic devices on rigid substrates has been remarkable, only few examples of flexible thin-film heterostructures are reported in the literature, all containing platinum group metals (PGMs). Systems based on Co/Ni may offer additional advantages with respect to devices containing PGMs, i.e., low damping and high spin polarization. Moreover, limiting the use of PGMs may relieve the demand for critical raw materials and reduce the environmental impact of related technologies, thus contributing to the transition toward a more sustainable future. Here, we discuss for the first time the realization of Co/Ni-based PMA-SAFs on polymer tapes and exploit it to obtain flexible giant magneto-resistive spin valves (GMR-SVs) with perpendicular magnetic anisotropy. Several combinations of buffer and capping layers (i.e., Pt, Pd, and Cu/Ta) are also investigated. High-quality flexible SAFs with a fully compensated antiferromagnetic region and SVs with a sizable GMR ratio (up to 4.4%), in line with the values reported in the literature for similar systems on rigid substrates, were obtained in all cases. However, we demonstrate that PGMs allows achieving the best results when used as a buffer layer, while Cu is the best choice as a capping layer to optimize the properties of the stacks. We justify the role of buffer and capping layers in terms of different interdiffusion mechanisms occurring at the interface between the metallic layers. These results, along with the high robustness of the samples’ properties against bending (up to 180°), indicate that complex and bendable Co/Ni-based heterostructures with reduced content of PGMs can be obtained on flexible tapes, allowing for the development of novel flexible and sustainable spintronic devices for applications in many fields including wearable electronics, soft robotics, and biomedicine.

Solar energy has become crucial in providing the world with an opportunity to reduce its carbon footprint, as well as fighting the consequences of climate change. Furthermore, Africa is at the forefront of the regions affected by climate change with a future expectancy of worsening consequences, in addition to being a region with various electricity complications, energy demands, and global greenhouse emissions contributions. Therefore, not only is Africa in major need of adopting efficient renewable energy technologies for their apparent future concerns but also Africa is already considered a region that has significant solar energy potential due to its abundant natural and renewable resources. Solar energy’s potential in Africa could not only be a solution to many of the continent’s complications, but it could also help the continent’s economy thrive The potential of solar energy in Africa as well as techniques to efficiently implement it has piqued literary interest a lot recently however, this paper aims to highlight through literature not only the potential and the technologies available for adoption but also the challenges complicating the implementation. This paper is split into four literary sections, first section puts forward the challenges facing Africa in the uptake of solar energy technologies including financial, technological, human resources, and environmental challenges. Then, in-depth discussions of the various solar energy technologies for potential adoption. Third, the biggest solar energy projects implemented in Africa are put forward. Finally, a thorough study of the aforementioned challenges, their current state, and the actions required to overcome them is presented in order to fully realize the potential of solar energy deployment across the continent.

Salt-inducible kinases (SIKs), a family of serine/threonine kinases, were found to be critical determinants of female fertility. SIK2 silencing results in increased ovulatory response to gonadotropins. In contrast, SIK3 knockout results in infertility, gonadotropin insensitivity, and ovaries devoid of antral and preovulatory follicles. This study hypothesizes that SIK2 and SIK3 differentially regulate follicle growth and fertility via contrasting actions in the granulosa cells (GCs), the somatic cells of the follicle. Therefore, SIK2 or SIK3 GC-specific knockdown (SIK2GCKDand SIK3GCKD, respectively) mice were generated by crossing SIK floxed mice with Cyp19a1pII-Cre mice. Fertility studies revealed that pup accumulation over 6 months and the average litter size of SIK2GCKDmice were similar to controls, although in SIK3GCKDmice were significantly lower compared to controls. Compared to controls, gonadotropin stimulation of prepubertal SIK2GCKDmice resulted in significantly higher serum estradiol levels, whereas SIK3GCKDmice produced significantly less estradiol. Cyp11a1, Cyp19a1,and StARwere significantly increased in the GCs of gonadotropin-stimulated SIK2GCKDmice. However, Cyp11a1 and StARremained significantly lower than controls in SIK3GCKDmice. Interestingly, Cyp19a1stimulation in SIK3GCKDwas not statistically different compared to controls. Superovulation resulted in SIK2GCKDmice ovulating significantly more oocytes, whereas SIK3GCKDmice ovulated significantly fewer oocytes than controls. Remarkably, SIK3GCKDsuperovulated ovaries contained significantly more preantral follicles than controls. SIK3GCKDovaries contained significantly more apoptotic cells and fewer proliferating cells than controls. These data point to the differential regulation of GC function and follicle development by SIK2 and SIK3 and supports the therapeutic potential of targeting these kinases for treating infertility or developing new contraceptives.

Background Patients with SARS-CoV-2 infection could develop severe disease requiring critical care admission. Case reports indicated high incidence of hypertriglyceridemia (HTG) in critically ill patients infected with SARS-CoV-2, which might be related to the drugs.Objective We sought to determine the risk factors associated with HTG in this population and to investigate the relationship between HTG and lipase.Methods A retrospective observational study was conducted at our hospital between March 1 and June 30, 2020. Patients were included if they were ≥18 years old, admitted to the intensive care unit (ICU), tested positive for SARS-CoV-2, and had triglycerides (TG) checked during their hospital stay.Results Of the 111 critically ill patients, 103 patients were included. Males comprised 88.3% of the sample. The median TG at baseline was 197.4 (IQR: 139.8-283) mg/dL. The lipase median level at baseline was 23.00 (IQR: 0.00-69.50) IU/L. The results of the mixed-effects logistic regression analysis indicated that patient-level variables, favipiravir use, blood glucose level, and propofol use were significantly associated with HTG. There was no relationship between lipase and TG levels over time. Furthermore, TG concentrations over time showed a similar trend to inflammatory markers.Conclusion and Relevance The incidence of clinically significant HTG was high and was associated with propofol and favipiravir use. HTG might reflect the high inflammatory state in these patients. Clinicians should look at the full picture before changing therapies based only on HTG. Our findings need to be replicated in a larger prospective study.

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Otitismediais an acute illness that specifically targets the middle ear. It affects around one-third of the pediatric population in the US. This study aimed to develop lecithin-based proniosomes to enhance the trans-tympanic permeation of the antimicrobial drug ofloxacin (OFX) and boost its antibacterial properties. Proniosomes were fabricated by the coacervation technique using a Box-Behnken design. The investigated factors were cholesterol amount (A), surfactant-to-drug ratio (B), and Brij percentage (C). The numerical optimization feature of Design-Expert® software was implemented to choose the optimum formula. The criteria for selection involved decreasing the polydispersity index (PDI) and particle size (PS) while maximizing the absolute value of zeta potential (ZP) and the percentage of entrapment efficacy (EE%). The formula with the highest desirability value (0.748), an EE% of 73.38 %, a PS of 625.35 nm, and a ZP of −44.20 mV was selected as the optimum formula. Additional investigations were conducted to illustrate the morphological appearance, release rate, stability, activity, and tolerability of the selected formula, such as invitro,ex vivo,microbiological,and invivotests. Results demonstrated that, compared to the OFX solution (2118.72 μg/cm2), the optimum formula was found to have better otic tolerance, augmented trans-tympanic permeation (3701.01 μg/cm2), and improved antibacterial activity. The aforementioned outcomes highlighted the capability of the OFX-loaded lecithin-based proniosomes to be used as a promising non-invasive delivery system for the treatment of otitismedia.

Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.

Porous silicon (n-PS) with diverse morphologies was prepared on silicon (Si) substrate via photo-electrochemical etching technique. We studies the structure, surface morphology, pore diameter, roughness, based on (XRD), (AFM), (SEM) at different etching time (5, 10 min) and current (10mA/cm2).

In this study, the development and assessment of a modified, efficient, and cost-efficient protocol for mDNA (metagenomic DNA) extraction from contaminated water samples was attempted. The efficiency of the developed protocol was investigated in comparison to a well-established commercial kit (Epicentre, Metagenomic DNA Isolation Kit for Water). The comparison was in terms of degree of shearing, yield, purity, duration, suitability for polymerase chain reaction and next-generation sequencing in addition to the quality of next-generation sequencing data. The DNA yield obtained from the developed protocol was 2.6 folds higher than that of the commercial kit. No significant difference in the alpha (Observed species, Chao1, Simpson and PD whole tree) and beta diversity was found between the DNA samples extracted by the commercial kit and the developed protocol. The number of high-quality sequences of the samples extracted by the developed method was 20% higher than those obtained by the samples processed by the kit. The developed economic protocol successfully yielded high-quality pure mDNA compatible with complex molecular applications. Thus we propose the developed protocol as a gold standard for future metagenomic studies investigating a large number of samples.

The Sheehan Irritability Scale (SIS) measures the frequency, severity, and impairment associated with irritability in psychiatric patients. The content validity of the SIS in patients with major depressive disorder (MDD) has not been evaluated. A cross-sectional, qualitative research study was conducted to assess the content validity of the SIS among patients with MDD. One-on-one interviews were conducted, starting with open-ended questions to evaluate the consistency of the SIS content with patient experiences of irritability. Participants then completed the SIS and cognitive interviews around the comprehension of the SIS content (instructions, items, response options). Participants included 24 patients diagnosed with MDD who had an inadequate response to an antidepressant treatment. The sample was: 50.4 mean years, 66.7% female, and 91.7% white racial background. All concepts on the SIS were spontaneously mentioned by at least one participant, and when probed about the symptoms, the majority of participants (66.7–100%) reported the concepts being part of their experience. The majority of participants (70.8–100%) understood the SIS instructions, items, and response scales. This study provides evidence of content validity of the SIS in patients diagnosed with MDD, supporting the use as a measure of irritability in patients with depression.

AbstractObjective:Compare long-term costs and outcomes of lurasidone to aripiprazole among adults with schizophrenia in the US who previously failed 1 atypical antipsychotic (olanzapine, risperidone, quetiapine, or ziprasidone) based on an indirect comparison of outcomes data from clinical trials.Methods:A 5-year Markov cohort model was developed to compare long-term effectiveness of lurasidone to aripiprazole, including total discontinuations, relapse rates, and hospitalization rates. Cost inputs included pharmacy, mental health, and medical costs associated with cardiometabolic risks (diabetes and cardiovascular [CV] events). Effectiveness inputs were derived from an indirect comparison of aripiprazole and lurasidone using common comparators from CATIE. Cardiometabolic risks were derived from claims data analysis for diabetes, weight change and CV events, and Framingham body mass index (BMI) risk equation. Cost inputs were derived from published sources and Red Book. Costs and outcomes were discounted at 3 and tested with sensitivity analyses.Results:Over 5 years, total discounted costs for lurasidone and aripiprazole patients were 86,480 and 90,500, respectively. During this period, the number of relapses per patient, hospitalizations per patient, diabetes rates, and CV events per 1000 patients, respectively, were estimated to be lower for lurasidone (0.442, 0.245, 7.29, and 37.3) than aripiprazole (0.478, 0.369, 7.36, and 37.8). Results were sensitive to lurasidone and aripiprazole hospitalization rates. At a willingness-to-pay threshold of 50,000 per hospitalization avoided, lurasidone had a 100 probability of being more cost-effective than aripiprazole.Limitations:The model was based on results from various comparative clinical trials. Differences in patient population and study methods may change estimates from the model. The model does not account for patient heterogeneity.Conclusions:Based on this model, when switching from another atypical antipsychotic, lurasidone had fewer relapses and hospitalizations with a lower incidence of diabetes and CV events than aripiprazole. Additionally, lurasidone may be less costly than aripiprazole among adults with schizophrenia.

Breast cancer is the most common form of cancer in Muslim women in Pakistan. The impact of the initial diagnosis, culture, religion, and psychosocial and psychological aspects of the disease is not well established. This qualitative study examined the experience and coping strategies used by patients with breast cancer in relation to its impact on their physical, mental health, religious, and family issues. Thirty patients with breast cancer were interviewed. Data were analyzed using thematic analysis. The patient's experience of breast cancer focused on the range of emotions felt throughout the illness trajectory, the importance of religion and family support on coping strategies used to manage the adverse effects of chemotherapy, and also the financial concerns. This is the first study to examine Pakistani Muslim women's views on the lived experience of breast cancer. This article provides clarification of the voiced experiences of women with breast cancer. The data not only highlight the role of religion and family support as essential coping strategies but also emphasize the issues of isolation, aggression, and anger as common responses to chemotherapy. Unique features of this study are women's need to seek spiritual support for their illness and the overriding innate characteristic of maternal responsibility. These cultural features require further analysis and research.

Background: Medication nonadherence is a significant problem among patients with bipolar disorder.Objective: To compare adherence and persistence among patients with bipolar disorder initiated on antipsychotics in a state Medicaid system over a 12 month follow-up period.Methods: Claims data for patients with bipolar disorder from a de-identified Medicaid database were examined. Patients were classified into 4 monotherapy treatment groups (risperidone, olanzapine, quetiapine, or typical antipsychotic) based on the first prescription filled between January 1, 1999, and December 31, 2001. Adherence and persistence were analyzed over a 12 month follow-up period. Adherence was measured using the Medication Possession Ratio (MPR). Persistence was defined as the total number of days from the initiation of treatment to therapy modification (ie, discontinuation, switching, or combination with another antipsychotic). Adjustment for confounding variables was undertaken using ordinary least-squares and Cox proportional hazard regression modeling.Results: The mean MPRs were 0.68 for risperidone (n = 231), 0.68 for olanzapine (n = 283), 0.71 for quetiapine (n = 106), and 0.46 for typical antipsychotics (n = 205). Patients initiated on typical antipsychotics were 23.6% less adherent than patients initiated on risperidone (p < 0.001). Mean persistence (days) was 194.8 for risperidone, 200.9 for olanzapine, 219.8 for quetiapine, and 179.2 for typical antipsychotics. Extended Cox regression modeling indicated no significant differences between antipsychotics in hazards of therapy modification within 250 days of initiation. However, patients initiated on typical antipsychotics were 5.2 times more likely to modify therapy compared with those initiated on risperidone after 250 days of antipsychotic therapy (p < 0.001).Conclusions: Adherence and persistence were similar between atypical antipsychotic groups. The typical antipsychotic group, however, demonstrated lower adherence and a greater likelihood of patients modifying therapy compared with the risperidone cohort

This work aimed to formulate clotrimazole (CLZ), a water-insoluble antifungal drug, into a chitosan-coated microemulsion system for achieving enhanced ocular delivery. In this study, CLZ loaded microemulsions were firstly prepared according to 22 × 31full factorial design in order to investigate the influence of different formulation variables on microemulsion properties. The selected microemulsion formulation (F4: oleic acid, Cremophor EL: Transcutol HP (1:1) and water (20, 70 and 10%, w/w, respectively)) showed nanosized spherical globules with a droplet size of 229.1 ± 0.989 nm, polydispersity index of 0.5085 ± 0.0095, and zeta potential of −33.3 ± 0.98 mV. The selected microemulsion was then coated with low molecular weight chitosan to increase the contact time with the eye surface. In vivostudies in albino rabbits demonstrated the superiority of chitosan-coated microemulsion over the uncoated microemulsion and drug suspension formulation concerning sustainment of antifungal activity over the eye surface. Moreover, the in vivo, ocular tolerance and histopathological studies conducted using male albino rabbits proved the safety of the prepared microemulsions after topical ocular application. Generally, the obtained results confirmed that CLZ chitosan-coated microemulsion could be promising for ocular CLZ delivery.

In this work, the effect of different substrate temperatures on the electrical and detection properties of Cu0z copper oxide thin film has been carried out using Reactive Pulsed Laser Deposition technique (RPLD). l = 1046 nm Q-switch Nd-YAG laser with (900 mj) laser energy's has been used to ablated pure copper target and deposited on the Silicon substrates. The X-ray diffraction in sour the formation of polycrystalline Cu2O nanostructure thin film.