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Graft Versus Host Disease (GVHD) is a major limitation to the success of allogeneic Hematopoietic Stem Cell Transplantation (HSCT) as Steroid-Refractory (SR) acute GVHD carries poor prognosis due to the absence of an efficacious second-line therapy. Mesenchymal Stem Cells (MSCs) which have immunosuppressive, immunomodulatory, and regenerative properties may become a highly effective therapeutic modality for SR-GVHD in the near future. MSCs have already been approved to treat childhood SR-GVHD in Japan, and they have been conditionally licensed in New Zealand and Canada. It is expected that MSCs will be approved for the treatment of SR-GVHD in adults in Europe, North America, and other parts of the world within a few years. Utilization of the recently introduced techniques including the use of MSC products such as exosomes and Extracellular Vesicles (ECVs) instead of the parent MSCs, robotic manufacturing technology, and genetic engineering of MSCs will ultimately overcome the remaining obstacles facing the widespread utilization of MSCs and their products as therapeutics not only in HSCT but also in other medical fields. The aim of this review is to provide an update on the remarkable progress achieved in the use of MSCs and their products in the field of HSCT.

Mesenchymal Stem Cells (MSCs) have antimicrobial, anti-inflammatory, immunomodulatory, and regenerative potentials. Additionally, utilization of MSCs in the clinical arena has been shown to be safe and well tolerated. Hence, this form of cellular therapy has gained particular attention in the treatment of several infectious disorders and their complications. MSCs have been successfully used in the treatment of the following infections and their complications: bacterial infections including complicated sepsis; viral infections including Human Immunodeficiency Virus (HIV), hepatitis B and C viruses, and Coronavirus disease (COVID-19) complicated by acute respiratory distress syndrome; parasitic infections including schistosomiasis, malaria, and Chagas disease; and mycobacterial infections including tuberculosis. The use of MSCs derived from certain sources and Extracellular Vesicles (ECVs) derived from MSCs has improved their efficacy and reduced their side effects. However, the clinical application of MSCs in the treatment of several infectious diseases still faces real challenges that need to be resolved. The current status of MSCs and the controversies related to their utilization in various infections will be thoroughly discussed in this review. 

The adjusted Hardy-Rogers result generalization for the fixed point is demonstrated in this study, validating our results utilizing an application.

The effect of known synthetic compounds Ivin (N-oxide-2,6-dimethylpyridine), Methyur (sodium salt of 6-methyl-2-mercapto-4-hydroxypyrimidine), Kamethur (potassium salt of 6-methyl-2-mercapto-4-hydroxypyrimidine) and new synthetic compounds, derivatives of pyrimidine (No. 1 - 7) on the rooting of isolated stem cuttings of haricot bean (Phaseolus vulgaris L.) variety Bilozernaya was studied. The growth regulatory activity of synthetic compounds Ivin, Methyur, Kamethur, and synthetic compounds, derivatives of pyrimidine (No. 1 - 7) was compared with the activity of auxins IAA (1H-indol-3-yl)acetic acid) and NAA (1-naphthylacetic acid). The conducted studies showed that the regulatory effect of synthetic compounds Ivin, Methyur, Kamethur, and synthetic compounds, derivatives of pyridine (No. 1 - 7) on the rooting of isolated stem cuttings of haricot bean was similar to the auxins IAA and NAA. The synthetic compounds Ivin, Methyur, and Kamethur, and synthetic compounds, derivatives of pyrimidine (No. 1, 4, 5, and 7) showed the highest auxin-like activity. The indicators of the total number of roots (pcs) and total length of roots (cm) obtained on isolated stem cuttings of haricot bean immersed in a water solution of synthetic compounds Ivin, Methyur, Kamethur and synthetic compounds, derivatives of pyridine (No. 1, 4, 5 and 7), used at a concentration of 10-7 M, statistically significantly exceeded similar indicators obtained on control isolated stem cuttings of haricot bean immersed in distilled water. The practical use of synthetic compounds Ivin, Methyur, Kamethur, and synthetic compounds, derivatives of pyrimidine (No. 1, 4, 5 and 7) is proposed to improve the vegetative propagation of haricot bean plants (Phaseolus vulgaris L.) and other plant species of the family Fabaceae by stem cuttings.

Intraovarian injection of autologous Platelet Lysate (PL) can be considered a potential therapeutic strategy for ovarian function rejuvenation. Especially, in women diagnosed with Poor Ovarian Response (POR) or Primary Ovarian Insufficiency (POI), the exogenous administration of the autologous platelet-derived growth factors, influence positively the regulation of the serum Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), and Anti-Mullerian Hormone (AMH) and Estradiol (E2). Therefore, the evaluation of the serum levels of the aforementioned hormones was performed on 10 participants with a mean age of 43 ± 4 years diagnosed with POR or POI, who received intraovarian PL injection monotherapy. The monitoring of the serum hormone levels was performed for 3 months. The results of this study clearly showed that all participants were characterized by elevated levels of FSH and LH and reduced levels of E2 and AMH, prior to the PL injection. However, the levels of all hormones started to change after the 1st month of follow-up monitoring. Moreover, 40% of the participants conceived successfully either by natural way or after in vitro Fertilization (IVF). Considering these, the intraovarian injection of autologous PL exhibited promising evidence regarding the altering of hormone levels at physiological values. Moreover, the contained PL growth factors were implicated in angiogenesis promotion and also in toleration of the inflammatory microenvironment, regulating positively ovarian function. In conclusion, the intraovarian autologous PL injection is considered a safe, effective, and tolerable therapeutic strategy in women with POR or POI. Moreover, the results of this study were very encouraging, especially for the women with infertility issues, who want their genetic offspring.

The ongoing COVID-19 pandemic has seen the evolution of the SARS-CoV-2 virus, resulting in the emergence of various concerning variants with unique biological characteristics. As the pandemic continues, it will be crucial to promptly evaluate the potential of any new variant to cause severe illness. The severity of the latest Omicron sublineages, including BA.5, XBB, BQ.1.18, BA.2, BA.2.75, and EG.5.1, is currently under assessment. This system provides valuable and essential information for rapidly assessing the threat posed by new versions of the virus.

This study delves into the forensic examination of textile fibers for identification through the application of the X-ray diffraction (XRD) technique. With the textile industry producing an array of materials, both natural and man-made fibers, the need to distinguish between them for forensic purposes becomes paramount. The primary objective of this research is to identify unique characteristics in fiber samples, differentiating between branded and non-branded company textiles. The focus is placed on fresh, unused cloth fibers obtained directly from shops. The study encompasses two broad categories of fibers: natural (such as cotton, silk, and wool) and man-made (including nylon, rayon, and polyester). Samples from both branded and non-branded textiles undergo analysis using XRD, a sophisticated method capable of revealing the crystallographic structure of materials. Results obtained from the XRD analysis unveil intensity peaks at various levels and degrees, providing distinctive patterns for individualization. Even within the same fiber category, such as polyester and cotton, discernible differences in intensity peaks facilitate the identification process. This research contributes to the advancement of forensic techniques by offering a reliable means of identifying textile fibers. The utilization of XRD not only allows for the differentiation between natural and man-made fibers but also enables discrimination among textiles produced by different companies. The implications of this study extend to forensic investigations, where the ability to precisely identify fibers can provide valuable evidence in criminal cases involving textiles.

A very unusual, interesting, and challenging case of a 24-year-old female who was born with three openings in the neck. The patient had chronic abdominal gaseous distention, recurrent abdominal pain, and constipation since early infancy. The patient presented in emergency with acute painful red, hot, and tender swelling in the left upper cervical area. Laboratory studies showed high inflammatory markers and a provisional diagnosis of abscess with a sinus was made. The patient underwent an emergency incision and drainage. Sinus recurred and a sinogram showed it to be a residual cyst in the left submandibular salivary gland. The total cyst excision was attempted with resultant recurrence and grade IV facial nerve palsy. Post-operatively recurrent infections caused by Methicillin-resistant Staphylococcus aureus (MRSA) required several courses of oral and intravenous broad-spectrum antibiotics with several hospital admissions with no resolution in sight. Subsequent ultrasound and magnetic resonance imaging showed a residual infected cyst, cutaneous sinus, and a fistula opening in the left ear canal. A diagnosis of branchial cyst type II of the first brachial cleft remnant with a fistula was established with bilateral branchial fistulas of the second branchial remnants and the associated colorectal hypoganglionosis based on radiological studies. The patient refused any further operative interventions. Therefore, the option of conservative treatment of hypoganglionosis with holobiotics consisting of prebiotics, probiotics and postbiotics, laxatives, dietary changes, lifestyle modifications, and dietary supplements started. All antibiotics were stopped. These therapies resulted in the resolution of residual first branchial remnants and recurrent MRSA infections with the improvement in the facial nerve palsy from grade V to grade III-IV together with an excellent cosmetic and functional result. The patient is doing well at follow-ups being infection-free for 18 months and repeat contrast-enhanced computed tomogram (CECT) has shown complete resolution of the residual cyst, sinus, and fistula with fibrosis.

Mesenchymal stem cells are heterogenous adult multipotent stromal cells that can be isolated from various sources including bone marrow, peripheral blood, umbilical cord blood, dental pulp, and adipose tissue. They have certain regenerative, anti-inflammatory, immunomodulatory, immunosuppressive, antimicrobial, and other properties that enable them to have several therapeutic and clinical applications including treatment of various autoimmune disorders; role in hematopoietic stem cell transplantation and regenerative medicine; treatment of skin, pulmonary and cardiovascular disorders; treatment of neurological and eye diseases; as well as treatment of various infections and their complications. Different factors including donor age, biological source, route of administration, and signaling pathways have an impact on the functions and consequently the clinical applications of mesenchymal stromal cells. The products of mesenchymal stem cells such as extracellular vesicles and exosomes reproduce the biological effects and most of the therapeutic actions of the parent stem cells. Genetic engineering and the use of specific mesenchymal stromal cell products have improved their clinical efficacy and decreased their adverse effects. However, despite the recent progress in the use of mesenchymal stem cells, the clinical application of these cells in the treatment of several diseases still faces real challenges that need to be resolved. The current status of mesenchymal stem cells and the controversies related to their clinical utilization in various disease conditions will be thoroughly discussed in this review.

Background: Nimodipine (NM), is a dihydropyridine calcium channel blocker with poor oral bioavailability (BA) of about 13% due to first-pass metabolism and P-gp efflux. Objective: The present work aimed to study the influence of the charge inducer and its combination with P-gp inhibitor to improve the oral bioavailability of NM by developing a suitable delivery system of Submicron Lipid Emulsion (SME). Methods: Five SME formulations of NM were prepared by homogenization followed by ultrasonication. Prepared SMEs were characterized for particle size, PDI, Zeta Potential (ZP), Entrapment Efficiency (EE), and drug content. In vitro, release studies were performed in 0.1N HCl and pH 6.8 phosphate buffer by open tube method. The physical stability of all NM–SMEs was tested by the individual effects of centrifugation, dilution (desorption stress), and storage. Bioavailability studies were conducted on male Wistar rats after oral administration of NM suspension and F1 to F5 SME formulations. Results and conclusion: Five NM- SMEs were developed with a mean size ranging from 93 - 137 nm, Zeta potential of – 26 ± 1 mV (negatively charged), +45.8 to +46.3 mV (positively charged), and PDI of 0.15 - 0.25. The in vitro release studies showed that relatively more cumulative percentage release of NM – SMEs in 0.1N HCl than in pH phosphate buffer during 24 hours. The physical stability of NM–SMEs indicated that they were stable to the effects of centrifugation, dilution, and storage. Pharmacokinetic (PK) studies showed that the oral bioavailability of NM in F4 SME was significantly higher than that of all other formulations. Taken together, the results indicated the development of a stable lipid-based carrier, F4 SME to improve the oral bioavailability of this drug by minimizing first-pass metabolism due to lymphatic transport, reducing the efflux by P-gp inhibition, and further, by increased uptake of the positively charged F4 SME globules by enterocytes. Future: The research study findings increase the possibility of developing NM F4 SME by the pharmaceutical industry for the patient’s benefit.

Bronchiolitis is one of the most common respiratory infections in children under 2 years of age predominantly caused by Respiratory syncytial virus and other viruses like influenza, Para influenza, and Adenovirus. Rhinovirus, etc. Most children have mild symptoms however bronchiolitis has also been well linked to severe morbidities and mortalities. Even though bronchiolitis has been well recognized for many years, there are still very few therapeutic strategies available beyond supportive management. There are many controversies about therapeutic management in bronchiolitis published in standard guidelines and research in this area. Management can be divided into pharmacological and supportive therapy. Evidence suggests that the current management of bronchiolitis is purely supportive consisting of oxygen supplementation, frequent suctioning, and maintaining good hydration and nutrition. Regarding pharmacological therapy, neither bronchodilators nor corticosteroids have significant efficacy in the treatment of bronchiolitis. However, some studies suggest that adrenaline and nebulizer 3% saline showed some benefit only in terms of outcome. The current recommendation also supports the use of Palivizumab as prophylaxis in certain groups of infants and young children.

Background: Clinician managers can play a crucial role in healthcare organizations, including hospitals, by combining their clinical expertise with managerial responsibilities. They bring valuable insights and firsthand experience of patient care to managerial positions, contributing to improved patient outcomes and hospital performance. However, they face unique challenges that require careful attention and solutions. Aim: This review aims to critically discuss the role of clinicians as managers, the challenges that they face, and how they exercise their influence in hospital settings. Key findings: The role of clinicians as managers is critical for effective leadership and delivery of high-quality patient care. Described as a two-way window, clinician managers bridge the gap between medicine and management by combining clinical expertise with managerial skills in a hybrid leadership approach. Studies have shown a positive impact on hospital performance, including enhanced quality care, improved patient outcomes, and potentially better financial performance. In addition, they play a vital role in fostering interdisciplinary collaboration and boosting staff engagement. However, challenges such as identity conflicts, and limited formal training, are present, especially for first-time managers. Conclusion: Adapting to the dual role of clinician and manager demands a mindset shift and the development of new skills, necessitating strategic support. This includes leadership education, organizational support, mentoring, and collaborative models to empower clinician managers. Targeted training programs, formal mentoring, and peer support networks equip them with essential skills, while workload management, well-being initiatives, and a culture of balance foster success and growth.

Introduction: Bleeding from varices is a severe complication in patients with cirrhosis. Despite its treatment has been well established in the last three decades the mortality can be still high. This study compares the epidemiological features and the bleeding-related outcomes of a group of patients published about ten years ago with a more recent group of 168 consecutive patients. Methods: The diagnosis, the treatment, and the main outcomes (5-day failure, 5-day and 6-week rebleeding, 5-day and 6-week mortality) of variceal bleeding were evaluated according to the current guidelines.Results: The number of patients with cirrhosis admitted for variceal bleeding every year has progressively decreased in the last ten years. The age sex and severity of liver disease, evaluated with Child Pugh and MELD scores, were comparable in the two series. In the more recent series, there were significantly fewer patients with HCV infection and more patients with alcohol-related cirrhosis. The main outcomes of bleeding were comparable too. Overall, at 6 weeks 36.4% of patients did not overcome the bleeding episode. Conclusion: The decreasing incidence of bleeding from varices is likely attributable to antiviral treatment of HCV and HBV and the larger diffusion of beta-blockers in primary prophylaxis. Despite the larger application of the gold standard therapy, the mortality of variceal bleeding remains high in patients with cirrhosis.

Penile cancer, a rare but highly morbid disease, primarily manifests as squamous cell carcinoma (PSCC) originating from the squamous cells of the glandular and preputial skin. Late-stage diagnosis is common due to social stigma, psychological barriers, and nonspecific initial symptoms, resulting in poor overall survival rates, especially in metastatic cases. This case report illustrates a 38-year-old man with advanced metastatic PSCC, showcasing severe systemic manifestations and delayed presentation of the disease. Despite aggressive treatment options, the patient opted for palliative care, succumbing to the disease months after his diagnosis. Risk factors for PSCC include HPV infection, phimosis, chronic inflammation, and lifestyle factors, with higher prevalence in regions of low socioeconomic status. The psychological and sexual burden of penile cancer is significant, impacting patients’ well-being, mental health, and quality of life. In conclusion, efforts to reduce the stigma associated with penile cancer are crucial to prompt early diagnosis and treatment initiation. Encouraging seeking medical attention for symptoms can enhance the chances of recovery and minimize the need for invasive treatments. Addressing the psychosocial impact of the disease is imperative for holistic patient care.

The drug and biopharmaceutical enterprises play a pivotal part in transforming healthcare through the incident and delivery of creative cures and remedies. This item explores the key facets of these areas, stressing their impact on healthcare.Pharmaceuticals, outlined as wealthy secondhand in the diagnosis, situation, or stop of disease, aim to restore, correct, or refine everyday functions. On the other hand, biopharmaceuticals (or biologicals) circumscribe sugars, proteins, nucleic acids, living containers, or tissues and are curative devices that arise natural beginnings to a degree persons, animals, or microorganisms. In contrast to common pills combined with synthetic processes, biopharmaceuticals are primarily acquired through unaffected processes, containing extraction from living constructions or production utilizing alteration of genetic material Table 1.•    Some usual biopharmaceuticals, originally gleaned from animals or persons, are immediately created through biotechnological advancements.•    For instance, healing insulin, previously gleaned from porcine pancreatic islets, is immediately made utilizing alteration of genetic material in yeast (Saccharomyces cerevisiae) or E. coli.•    Biopharmaceuticals caused by alteration of genetic material usually fall into three classifications:•    Substances nearly equal to the body’s own key signaling proteins.•    Monoclonal antibodies look like those caused by apiece human immune plan against bacteria.•    Receptor builds (fusion proteins) established uniformly happening receptors connected to the immunoglobulin frame.Examples includeFrom living systems: Whole blood and ancestry parts, organs and fabric transplants, stem containers, antibodies for inactive immunization, polluted microbiota, human bosom milk, and human reproductive containers.Produced by recombinant DNA: Blood determinants, fabric plasminogen activators, hormones, hematopoietic growth determinants, interferon, interleukin-located produce, vaccines, monoclonal antibodies, tumor loss determinants, therapeutic enzymes.•    Key dispute Pharmaceutical manufacturing•    Biopharmaceuticals•    Healthcare strike•    Innovative medicines•    Therapeutic fragments•    Recombinant DNA technologies•    Personalized cure•    Gene medicines•    Regulatory processes.

Today’s need for renewable energy combined with modern societies' reliability on on-demand power leads us to find solutions that can store excess or produce directly to storage for later use. A MOlecular Solar Thermal (MOST) based on norbornadiene/quadricyclane(NBD/QC) does the latter with an isomeric photoswitching molecule pair. The theoretical studies of molecular solar thermals (MOST) provide a needed understanding of potential synthetic candidates. We have investigated an array of more complex solvation models for the norbornadiene/quadricycle (NBD/QC) photoswitch and the impacts of the models on the first absorption energy. Our results have been obtained with various density functional theoretical methods and basis sets.

Forеst dеgradation has bеcomе incrеasingly pronouncеd in rеcеnt timеs due to shifts in climatе pattеrns and prolongеd drought pеriods. This invеstigation aims to cultivatе high-quality vеgеtation and gain insights into thеir еcophysiological rеsponsеs undеr conditions of watеr strеss. Spеcifically, wе conductеd еxpеrimеnts on 6-month-old individuals from two dеciduous spеciеs (Quеrcus subеr and Cеratonia siliqua) and two conifеrs (Tеtraclinis articulata and Cеdrus at-lantica), subjеcting thеm to watеr strеss conditions. Wе mеasurеd and analyzеd both thе basic (Ψb) and minimum (Ψm) lеaf watеr potеntials, factoring in climatic variablеs for all four forеst spеciеs. Our findings rеvеal that Quеrcus subеr еxhibits morе nеgativе valuеs, with a basic lеaf watеr potеntial of -0. 42 MPa and a minimum lеaf watеr potеntial of -1. 43 MPa, comparеd to thе othеr studiеd forеst spеciеs. On thе contrary, Cеdrus atlantica displays lеss nеgativе valuеs for thе minimum lеaf watеr potеntial, rеcording -0. 89 MPa. Thеsе outcomеs еnablе us to idеntify thе spеciеs displaying grеatеr rеsiliеncе against watеr strеss and climatе fluctuations. Nеvеrthеlеss, they also prompt broadеr inquiriеs into thе undеrlying mеchanisms govеrning watеr utilization in forеst flora. 

The current study aimed to investigate the effect of using a pilates exercise program on improving body mass index and body composition of non-physically active working women. The participants of the study were (16) working women at the University of Basrah, Iraq. A pre-posttest was utilized to collect the data, (after a 12-week cycle of exercises) in Pilates groups, the results of the study showed that there were statistically significant differences at (α ≤ 0.05) in the women’s mean scores on body mass index and body composition. The study concluded that the pilates exercise program is effective in the improvement of body mass index and body composition of non-physically active working women.

Being hospitalized or undergoing a surgical procedure may be quite an isolating and lonely experience. This review explored loneliness in the hospital and surgical setting, and highlights the emotional and psychological challenges experienced by patients during their healthcare journey. While hospitals traditionally provide medical and surgical care for a wide array of conditions, the irony lies in their potential to disrupt one’s daily routines, contribute to loss of control, prolong hospital stays, and limit connections with family and loved ones leading to negative psychological well-being and intensifying feelings of loneliness. The implications of loneliness in the hospital and surgical contexts are discussed along with recommendations for improving the healthcare system’s response to the negative health consequences associated with loneliness. Coping strategies are discussed, including social support mechanisms, and approaches to healthy behaviors, i.e. mindfulness, which contribute to mitigating loneliness, in the context of hospitalizations and surgery.

Known since antiquity, migraine is a complex primary disorder, an episodic painful Autonomic Nervous System (ANS) storm, generally following the stress/post-stress phase. Despite exhaustive study of neuropeptides, neurochemicals, molecules, neurogenetics, neuroimaging along with animal and human experiments over the last 50 years, the scientific basis of migraine remains unknown. Straddling eight decades from Cortical Spreading Depression (CSD) to Calcitonin-Gene Related Peptide (CGRP) and its antagonists, exponentially increasing data have failed to create a gestalt synthesis. This article lays cohesive and robust fundamental principles for the comprehension and management of migraine. The continuum between migraine and non-congestive Primary Open-Angle Glaucoma (POAG), Normal Tension Glaucoma (NTG), or Low-Tension Glaucoma (LTG) is advancing. The case of sustained remission of migraine attacks (> 75%) over 3 years - 5 years with ocular hypotensive topical Bimatoprost Ophthalmic Solution (BOS) 0.3% in an N-of-1 trial in 3 patients with refractory migraine is presented. A cause-effect-adaptive process underlies the ANS-stress/post-stress-linked biology of migraine. Vasopressin-serotonin-norepinephrine ‘homeostatic-adaptive system’ Lowers Intraocular Pressure (IOP), while enhancing anti-stress, antinociception, vasomotor, and behaviour control functions, thereby selectively decreasing algogenic neural traffic in the ophthalmic division of trigeminal nerve (V1), and, raising the threshold to develop migraine. Striking migraine headache-aborting feature of vomiting is also likely linked to a several hundred-fold increase in arginine-vasopressin secretion. Eye-cover tests and self-ocular digital displacement are essential to studying the visual aura. Real-time physical displacement of Scintillating Scotoma (SS) and floating ‘stars’ is reported. The basis of spontaneous onset and offset, self-limited duration of migraine attacks, as well as female preponderance, and age/menopause decline in prevalence, are elucidated. Intraocular implants with long-term ocular hypotensive effects, including bimatoprost, are the future of migraine management. Controlled trials are required to establish the migraine-preventive effect of topical bimatoprost, a revolutionary advance in neuroscience.