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2.
Int J Low Extrem Wounds ; : 15347346241241578, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592472

RESUMO

Colostrum has been shown to be suitable for oral and/or topical applications. Colostrum decreases the amount of discharge from wounds and also accelerates healing, leading to a decrease in the number of dressings. In this study, 40 patients with chronic non-healing wounds were divided into two groups, considering the inclusion and exclusion criteria. Group I included 15 patients with conventional dressings, and Group II included 25 patients with added topical colostrum dressings. All patients were assessed at the time of presentation and after 21 days. The results of the present study indicate that colostrum powder dressings may be used as an adjunct in the management of chronic non-healing wounds.

3.
Lancet Reg Health Am ; 33: 100728, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38616918

RESUMO

Background: Sinusoidal obstruction syndrome is a potentially fatal complication following hematopoietic cell transplantation, high-intensity chemotherapies and increasingly seen with calicheamicin based leukemia therapies. Paediatric specific European Society for Blood and Marrow Transplantation (pEBMT) diagnostic criteria have demonstrated benefit in single center studies compared to historic criteria. Yet, the extent to which they have been universally implemented remains unclear. Methods: We conducted a retrospective multi-centre study to examine the potential impact of the Baltimore, modified Seattle and pEBMT criteria on the incidence, severity, and outcomes of sinusoidal obstruction syndrome among paediatric hematopoietic cell transplantation patients. Findings: The incidence of sinusoidal obstruction syndrome in this cohort (n = 488) was higher by pEBMT (21.5%) vs historic modified Seattle (15.6%) and Baltimore (7.0%) criteria (p < 0.001). Application of pEBMT criteria identified 44 patients who were not previously diagnosed with sinusoidal obstruction syndrome. Overall, 70.5% of all patients diagnosed with sinusoidal obstruction syndrome ultimately developed very severe disease and almost half of diagnosed patients required critical care support. Overall survival was significantly lower in patients who were diagnosed with sinusoidal obstruction syndrome vs those who were not. Interpretation: Taken together, pEBMT criteria may be a sensitive method for prompter diagnosis of patients who subsequently develop severe/very severe sinusoidal obstruction syndrome. To our knowledge, this is the first multi-centre study in the United States (US) to demonstrate that pEBMT guidelines are associated with earlier detection of sinusoidal obstruction syndrome. Since early initiation of definitive treatment for sinusoidal obstruction syndrome has been associated with improved survival in paediatric patients and implementation of pEBMT criteria appears feasible in the US, universal adoption should facilitate prompter diagnosis and lead to improved outcomes of children with sinusoidal obstruction syndrome. Funding: None.

4.
Cureus ; 16(3): e55959, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38601371

RESUMO

Background Diabetic patients exhibit increased platelet activity. Insulin inhibits the activation of platelets. Therefore, a relative or absolute deficiency of insulin would increase platelet reactivity. The younger (larger) platelets are also more metabolically and enzymatically active. If detected early, microvascular complications could alert us regarding the possible macrovascular complications. Thus, the aims and objectives of the present study were to determine platelet indices in patients with type 2 diabetes mellitus with controls (non-diabetics) and to find an association of platelet indices with microvascular complications.  Material & methods In this prospective case-control study conducted from 2021 to 2022 (2 years), a total number of 200 subjects were taken and were divided into two groups of 100 each, cases (I) and controls (II). The cases included patients of diabetes mellitus (DM) of a duration of more than 5 years, which were further divided into two groups of 50 each, IA and IB. Group IA consisted of patients with diabetes mellitus of a duration of more than five years with at least one microvascular complication and group IB was diabetics of more than five years duration without any microvascular complications, which includes diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. An automated cell counter (Thermo Fisher Scientific, Waltham, MA, US) provided hemoglobin values along with the platelet count and platelet indices, i.e. mean platelet volume (MPV), platelet large cell ratio (P-LCR), and platelet distribution width (PDW). Results The present study consisted of 200 subjects divided into 2 groups of 100 each, cases (I) and controls (II). The average MPV (9.4-12.3 femtolitre) in diabetics was 12.089±1.450 fL as compared to the controls where it was 9.464±1.424 fL with a statistically significant p-value of 0.001. PDW among the cases was 16.868±2.352 fL while in controls, it was 12.753±10.559 fL (p=0.001). The mean P-LCR was 34.975±8.056% among the cases, in comparison to the mean P-LCR among the controls, which was 26.031±7.004 (p=0.001). In this study, the MPV, PDW, and P-LCR were significantly raised in individuals having diabetes with microvascular complications when compared with patients without complications. The mean MPV in diabetics with complications was 12.5960±0.95660 fL and in those without complications was 11.5820±1.67609 fL (with a p-value of P = 2×10-3)which is statistically significant. Similar results were obtained in cases of PDW and P-LCR. The mean PDW in diabetics with complications was 17.1140±2.58228 fL and without complications was 15.6220±2.10532 fL ((with a p-value of P = 2×10-3)). The mean P-LCR in diabetics with microvascular complications was 35.408±3.5490% and without complications was 33.542±4.8694% (with a p-value of P = 3.1×10-3). Conclusion Based on the findings of the present study, there is a statistical correlation between type 2 diabetes and variations in platelet indices, resulting in the associated microvascular complications. Higher MPV, PDW, and P-LCR values suggest that these parameters are more reliable predictors of early vascular complications in individuals with type 2 diabetes mellitus and can be utilized as an easy-to-use, low-cost method. They are a readily available, economical, practical, noninvasive, and simple-to-understand approach for assessing platelet dysfunction, which in turn helps anticipate the existence of microvascular complications.

6.
Int J Low Extrem Wounds ; : 15347346241246339, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38659348

RESUMO

Chronic wounds have long been a significant public health concern, but the true impact of these wounds is unknown since research designs and measuring techniques vary, leading to inconsistent estimates. The definition of a wound is a loss of epithelial continuity caused by damage to the tissue. The following conditions can cause chronic wounds: panniculitis, pyoderma gangrenosum, traumatic, neurological, metabolic, hematologic, neoplastic, or infection-related. The growing global incidence of diabetes and the aging population necessitate greater attention to chronic wounds. Regrettably, it is sad that significant healthcare institutions have overlooked wound research. The study of health-related illnesses and occurrences in particular populations, including their distribution, frequency, and determinants, and the application of this research to control health problems.

7.
J Psychopharmacol ; 38(4): 311-317, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38494948

RESUMO

As Faculty of the British Association for Psychopharmacology course on child and adolescent psychopharmacology, we present here what we deem are the most common pitfalls, and how to avoid them, in child and adolescent psychopharmacology. In this paper, we specifically addressed common pitfalls in the pharmacological treatment of attention-deficit/hyperactivity disorder, anxiety, bipolar disorder, depression, obsessive-compulsive disorder and related disorders, and tic disorder. Pitfalls in the treatment of other disorders are addressed in a separate paper (part II).


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno Obsessivo-Compulsivo , Psicofarmacologia , Transtornos de Tique , Criança , Humanos , Adolescente , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Tique/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Comorbidade
8.
J Psychopharmacol ; 38(4): 318-323, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38494873

RESUMO

As Faculty of the British Association for Psychopharmacology course on child and adolescent psychopharmacology, we present here what we deem are the most common pitfalls, and how to avoid them, in child and adolescent psychopharmacology. In this paper, we specifically addressed common pitfalls in the pharmacological treatment of autism and intellectual disability, eating disorders, neuropsychiatric correlates of epilepsy, and psychosis. Pitfalls in relation to the treatment of other disorders are addressed in a separate paper (Part I).


Assuntos
Transtorno Autístico , Transtornos da Alimentação e da Ingestão de Alimentos , Deficiência Intelectual , Psicofarmacologia , Transtornos Psicóticos , Criança , Adolescente , Humanos
9.
Ann Thorac Med ; 19(1): 87-95, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444990

RESUMO

OBJECTIVE: The aim of this study was to estimate the predictors, associations, and outcomes of COVID-19-associated pulmonary disease (CAPA) in the United States. STUDY DESIGN AND METHODS: This retrospective cohort study was performed by using the National Inpatient Sample Database 2020 to identify coronavirus disease 2019 (COVID-19) and CAPA hospitalizations. Baseline variables and outcomes were compared between COVID-19 hospitalizations without aspergillosis and those with aspergillosis. These variables were then used to perform an adjusted analysis for obtaining predictors and factors associated with CAPA and its inhospital mortality. RESULTS: Of the 1,020,880 hospitalizations identified with the principal diagnosis of COVID-19, CAPA was identified in 1510 (0.1%) hospitalizations. The CAPA cohort consisted of a higher proportion of males (58%) as well as racial and ethnic minorities (Hispanics, Blacks, and others [including Asian or Pacific islanders, native Americans]). Inhospital mortality was significantly higher (47.35% vs. 10.87%, P < 0.001), the average length of stay was longer (27.61 vs. 7.29 days, P < 0.001), and the mean cost per hospitalization was higher ($121,560 vs. $18,423, P < 0.001) in the CAPA group compared to COVID-19 without aspergillosis. History of solid organ transplant, chronic obstructive pulmonary disease, and venous thromboembolism were associated with higher odds of CAPA among other factors. The use of invasive mechanical ventilation (adjusted odds ratio [aOR] 6.24, P < 0.001), acute kidney injury (aOR 2.02, P = 0.028), and septic shock (aOR 2.07, P = 0.018) were associated with higher inhospital mortality in the CAPA cohort. CONCLUSION: While CAPA is an infrequent complication during hospitalizations for COVID-19, it significantly increases all-cause mortality, prolongs hospital stays, and leads to higher hospital expenses compared to COVID-19 cases without aspergillosis.

10.
Vasc Med ; : 1358863X241228271, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38469821

RESUMO

Erdheim-Chester disease (ECD) is a rare 'L' (Langerhans) group histiocytic neoplasm that affects a multitude of organ systems, causing osteosclerotic bone lesions, periaortic encasement ('coated' aorta), retroperitoneal fibrosis involving kidneys and ureters ('hairy kidney'), and infiltration of the central nervous system. Cardiovascular involvement can occur in up to 70% of patients and is usually found during computed tomography/magnetic resonance imaging evaluation. When present, cardiovascular symptoms can have wide variability in presentation from asymptomatic to pericarditis, fatal cardiac tamponade, myocardial infarction, conduction abnormalities, heart failure, renal artery stenosis, and claudication. Cardiac involvement found on imaging includes right atrial pseudotumor, right atrioventricular groove infiltration, and pericardial effusions. ECD can involve the large- and medium-sized arteries, often seen as periarterial thickening (commonly coating the aorta) with stenosis/occlusion. Although more cardiovascular ECD cases have begun to be published in the literature, more data are needed on the outcomes of these patients, as well as how cardiovascular manifestations respond to treatment of ECD.

11.
Ann Thorac Surg ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38360341

RESUMO

BACKGROUND: Differences in outcomes by indication for venoarterial extracorporeal life support (VA-ECLS) are poorly described. We hypothesized that patients on VA-ECLS for acute pulmonary embolism (PE) have fewer complications and better survival than patients on VA-ECLS for other indications. METHODS: All patients ≥18 years on VA-ECLS from the Extracorporeal Life Support Organization global registry (2010-2019) were evaluated (n = 29,842). After excluding patients aged >79 years (n = 729) and those with incomplete indication data (n = 2530), patients were stratified by VA-ECLS indication for PE vs all other indications. The association between being discharged alive and each type of complication with VA-ECLS indication was assessed. RESULTS: Of 26,583 patients included in the analysis, 978 (3.7%) were on VA-ECLS for a primary diagnosis of acute PE. Acute PE patients were younger (53.1 vs 56.7 years, P < .001) and were more likely to be women (52.1% vs 32.3%, P < .001). Patients who underwent VA-ECLS for acute PE were 78% more likely to be discharged alive vs patients supported with VA-ECLS for other reasons (P < .001). Acute PE patients had fewer cardiovascular and renal complications (26.6% vs 38.0% and 31.1% vs 39.4%, respectively; adjusted P < .001). Acute PE patients had higher odds of having clots and mechanical complications (8.7% vs 7.9% and 16.7% vs 14.6%, respectively; adjusted P < .001). CONCLUSIONS: Patients undergoing VA-ECLS for acute PE have higher odds of survival to hospital discharge compared with those supported for other indications. Additionally, VA-ECLS in this population is associated with fewer cardiovascular and renal complications but higher mechanical complications.

12.
Ann Afr Med ; 23(1): 100-103, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38358179

RESUMO

The pediatric age group with massive hydrocephalus posted for ventriculoperitoneal (VP) shunt presents a lot of confrontation to anesthesiologists due to macrocephalus and associated congenital anomalies. Here, we presented a case report with massive hydrocephalus with aqueduct stenosis, posted for VP shunt placement, and retained a difficult airway.


RésumésLe grouped'âgepédiatrique avec unehydrocéphalie massive affichée pour un shunt ventriculopéritonéal (VP) présente beaucoup de confrontation à l'anesthésisteen raison de la macrocéphalieet des anomalies congénitalesassociées. Ici, nous avonsprésentéun rapport de casd'hydrocéphalie massive avec sténose de l'aqueduc, affiché pour la miseen place d'un shunt VP, et conservéunevoierespiratoire difficile. Mots-clés : Pédiatrique, Voiesrespiratoiresdifficiles, hydrocéphalie, dérivationventriculopéritonéale.


Assuntos
Anestésicos , Hidrocefalia , Criança , Humanos , Hidrocefalia/complicações , Hidrocefalia/cirurgia , Derivação Ventriculoperitoneal/efeitos adversos , Estudos Retrospectivos
13.
Artigo em Inglês | MEDLINE | ID: mdl-38367199

RESUMO

PURPOSE OF REVIEW: Tension-type headache (TTH) continues to be the most prevalent type of headache across all age groups worldwide, and the global burden of migraine and TTH together account for 7% of all-cause years lived with disability (YLDs). TTH has been shown to have a prevalence of up to 80% in several studies and presents a wide range and high variability in clinical settings. The aim of this review is to identify gaps in diagnostics, nosology, and variability in the treatment of children and adolescents who present with headaches without an identifiable etiology. RECENT FINDINGS: Migraine and TTH have been debated to have more similarities than distinctions, increasing chances of misdiagnosis and leading to significant cases diagnosed as probable TTH or probable migraine. The lack of specificity and sensitivity for TTH classification often leads to the diagnosis being made by negating associated migraine symptoms. Although pathology is not well understood, some studies have suggested a neurological basis for TTH, in need of further validation. Some research indicates that nitric oxide signaling plays an integral part in the pain mechanisms related to TTH. Analgesics and non-steroidal anti-inflammatories are usually the first lines of treatment for children with recurring headaches, and additional treatment options include medication and behavioral therapies. With high prevalence and socioeconomic burden among children and adolescents, it's essential to further study Tension-type headaches and secondary headaches without known cause and potential interventions. Treatment studies involving randomized controlled trials are also needed to test the efficacy of various treatments further.

14.
Health Technol Assess ; 28(6): 1-94, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38329108

RESUMO

Background: Stepping Stones Triple P is an adapted intervention for parents of young children with developmental disabilities who display behaviours that challenge, aiming at teaching positive parenting techniques and promoting a positive parent-child relationship. Objective: To evaluate the clinical and cost-effectiveness of level 4 Stepping Stones Triple P in reducing behaviours that challenge in children with moderate to severe intellectual disabilities. Design, setting, participants: A parallel two-arm pragmatic multisite single-blind randomised controlled trial recruited a total of 261 dyads (parent and child). The children were aged 30-59 months and had moderate to severe intellectual disabilities. Participants were randomised, using a 3 : 2 allocation ratio, into the intervention arm (Stepping Stones Triple P; n = 155) or treatment as usual arm (n = 106). Participants were recruited from four study sites in Blackpool, North and South London and Newcastle. Intervention: Level 4 Stepping Stones Triple P consists of six group sessions and three individual phone or face-to-face contacts over 9 weeks. These were changed to remote sessions after 16 March 2020 due to the coronavirus disease 2019 pandemic. Main outcome measure: The primary outcome measure was the parent-reported Child Behaviour Checklist, which assesses the severity of behaviours that challenge. Results: We found a small non-significant difference in the mean Child Behaviour Checklist scores (-4.23, 95% CI -9.98 to 1.52, p = 0.146) in the intervention arm compared to treatment as usual at 12 months. Per protocol and complier average causal effect sensitivity analyses, which took into consideration the number of sessions attended, showed the Child Behaviour Checklist mean score difference at 12 months was lower in the intervention arm by -10.77 (95% CI -19.12 to -2.42, p = 0.014) and -11.53 (95% CI -26.97 to 3.91, p = 0.143), respectively. The Child Behaviour Checklist mean score difference between participants who were recruited before and after the coronavirus disease 2019 pandemic was estimated as -7.12 (95% CI -13.44 to -0.81) and 7.61 (95% CI -5.43 to 20.64), respectively (p = 0.046), suggesting that any effect pre-pandemic may have reversed during the pandemic. There were no differences in all secondary measures. Stepping Stones Triple P is probably value for money to deliver (-£1057.88; 95% CI -£3218.6 to -£46.67), but decisions to roll this out as an alternative to existing parenting interventions or treatment as usual may be dependent on policymaker willingness to invest in early interventions to reduce behaviours that challenge. Parents reported the intervention boosted their confidence and skills, and the group format enabled them to learn from others and benefit from peer support. There were 20 serious adverse events reported during the study, but none were associated with the intervention. Limitations: There were low attendance rates in the Stepping Stones Triple P arm, as well as the coronavirus disease 2019-related challenges with recruitment and delivery of the intervention. Conclusions: Level 4 Stepping Stones Triple P did not reduce early onset behaviours that challenge in very young children with moderate to severe intellectual disabilities. However, there was an effect on child behaviours for those who received a sufficient dose of the intervention. There is a high probability of Stepping Stones Triple P being at least cost neutral and therefore worth considering as an early therapeutic option given the long-term consequences of behaviours that challenge on people and their social networks. Future work: Further research should investigate the implementation of parenting groups for behaviours that challenge in this population, as well as the optimal mode of delivery to maximise engagement and subsequent outcomes. Study registration: This study is registered as NCT03086876 (https://www.clinicaltrials.gov/ct2/show/NCT03086876?term=Hassiotis±Angela&draw=1&rank=1). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: HTA 15/162/02) and is published in full in Health Technology Assessment; Vol. 28, No. 6. See the NIHR Funding and Awards website for further award information.


Research shows that in children without learning disabilities, parenting groups which support parents to develop skills to manage behaviours that challenge in their child can be helpful. The National Institute of Health and Care Excellence recommended that more research was needed to strengthen the evidence for such interventions for children with moderate to severe learning disability who are more likely to display behaviours that challenge in England. In this study, we tested in real-world conditions a programme called level 4 Stepping Stones Triple P, which has shown positive results in trials outside of the United Kingdom. Trained therapists delivered six groups and three individual sessions over 9 weeks to parents of children aged 30­59 months with moderate to severe learning disabilities. Two hundred and sixty-one parents were allocated to one of two arms by chance (randomisation): one received Stepping Stones Triple P and treatment as usual and the other treatment as usual only. Treatment as usual included support and advice by general practitioners or community child development teams. Our primary outcome was parent-reported child behaviour at 12 months after randomisation. We also collected data on other outcomes and carried out interviews with parents, service managers and therapists to find out their views about Stepping Stones Triple P. We did not find that Stepping Stones Triple P reduces behaviours that challenge in the child more than treatment as usual at 12 months. However, when we looked at people who received more than half of the sessions, there was a larger reduction in behaviours which suggests that Stepping Stones Triple P works for families if they attend the full programme. Stepping Stones Triple P seems to be good value for money, as we found that at 12 months (covering 10 months of costs), the Stepping Stones Triple P cost £1058 less than treatment as usual from a health and social care perspective. As such, Stepping Stones Triple P is fairly cheap to deliver and a suitable early intervention for behaviours that challenge especially because of positive feedback from parents. Throughout the trial, we included a Parent Advisory Group that oversaw study materials, interview topic guides and promotion of the study.


Assuntos
COVID-19 , Deficiência Intelectual , Pré-Escolar , Humanos , Análise Custo-Benefício , Londres , Qualidade de Vida , Método Simples-Cego
15.
Cureus ; 16(1): e51728, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38318589

RESUMO

The varicella-zoster virus reactivates to cause herpes zoster, commonly referred to as shingles. Shingles traditionally manifest as itchy vesicles in a dermatomal distribution, accompanied by related constitutional symptoms in immunocompetent patients. Usually, the rash resolves completely in seven to ten days. Herpetic neuralgia is the most typical herpes zoster consequence. Around 1% to 5% of individuals have motor impairments, with Ramsay-Hunt syndrome being the most prevalent ailment. Additional problems encompass abdominal pseudohernia, paralytic ileus/colonic pseudo-obstruction, hemidiaphragm paralysis, bladder dysfunction, localized paresis, constipation, and visceral neuropathy. Herpes zoster infection typically involves the posterior root ganglia, and most of the symptoms are sensory. Motor involvement can occur in the same distribution but is relatively uncommon. Segmental zoster paresis is a rare motor complication of herpes zoster, mimicking an abdominal hernia, which has an incidence of approximately 0.7%, but it needs no surgery different from the real abdominal wall hernia. In this case report, we describe a patient who, three weeks after developing a herpes zoster rash, acquired an abdominal protrusion, i.e., herpes-induced pseudohernia.

16.
BMJ Case Rep ; 17(2)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38423579

RESUMO

Aplastic anaemia is often associated with recent viral illnesses to include EBV and parvovirus along with certain medications such as anticonvulsants and sulfa containing antibiotics. We describe a case report of a female patient in her 70s who presented with pancytopenia after being treated with nitrofurantoin and ciprofloxacin for suspected urinary tract infection. She underwent an extensive workup to rule out alternative aetiologies of her pancytopenia to include a broad viral, autoimmune and malignancy evaluation which were unrevealing. Given her recent exposure to ciprofloxacin and nitrofurantoin and marrow recovery following removal of these agents, it was presumed that antibiotic exposure was the underlying cause of her aplastic anaemia.


Assuntos
Anemia Aplástica , Antibacterianos , Infecções Urinárias , Feminino , Humanos , Anemia Aplástica/complicações , Anemia Aplástica/tratamento farmacológico , Antibacterianos/efeitos adversos , Ciprofloxacina/efeitos adversos , Nitrofurantoína/efeitos adversos , Pancitopenia/induzido quimicamente , Pancitopenia/complicações , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/complicações , Idoso
18.
Curr Drug Deliv ; 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38279740

RESUMO

The field of fiber technology is a dynamic and innovative domain that offers novel solutions for controlled and targeted therapeutic interventions. This abstract provides an overview of key aspects within this field, encompassing a range of techniques, applications, commercial developments, intellectual property, and regulatory considerations. The foundational introduction establishes the significance of fiber-based drug delivery systems. Electrospinning, a pivotal technique, has been explored in this paper, along with its various methods and applications. Monoaxial, coaxial, triaxial, and side-by-side electrospinning techniques each offer distinct advantages and applications. Centrifugal spinning, solution and melt blowing spinning, and pressurized gyration further contribute to the field's diversity. The review also delves into commercial advancements, highlighting marketed products that have successfully harnessed fiber technology. The role of intellectual property is acknowledged, with patents reflecting the innovative strides in fiber-based drug delivery. The regulatory perspective, essential for ensuring safety and efficacy, is discussed in the context of global regulatory agencies' evaluations. This review encapsulates the multidimensional nature of fiber technology in drug delivery and pharmaceuticals, showcasing its potential to revolutionize medical treatments and underscores the importance of continued collaboration between researchers, industry, and regulators for its advancement.

19.
Metabolites ; 14(1)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38248866

RESUMO

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global health challenge, further compounded by the issue of antimicrobial resistance (AMR). AMR is a result of several system-level molecular rearrangements enabling bacteria to evolve with better survival capacities: metabolic rewiring is one of them. In this review, we present a detailed analysis of the metabolic rewiring of Mtb in response to anti-TB drugs and elucidate the dynamic mechanisms of bacterial metabolism contributing to drug efficacy and resistance. We have discussed the current state of AMR, its role in the prevalence of the disease, and the limitations of current anti-TB drug regimens. Further, the concept of metabolic rewiring is defined, underscoring its relevance in understanding drug resistance and the biotransformation of drugs by Mtb. The review proceeds to discuss the metabolic adaptations of Mtb to drug treatment, and the pleiotropic effects of anti-TB drugs on Mtb metabolism. Next, the association between metabolic changes and antimycobacterial resistance, including intrinsic and acquired drug resistance, is discussed. The review concludes by summarizing the challenges of anti-TB treatment from a metabolic viewpoint, justifying the need for this discussion in the context of novel drug discovery, repositioning, and repurposing to control AMR in TB.

20.
Int J Biol Macromol ; 254(Pt 2): 127898, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37939768

RESUMO

The ADP ribosylation factor like protein 15 (ARL15) gene encodes for an uncharacterized GTPase associated with rheumatoid arthritis (RA) and other metabolic disorders. Investigation of the structural and functional attributes of ARL15 is important to position the protein as a potential drug target. Using spectroscopy, we demonstrated that ARL15 exhibits properties inherent of GTPases. The Km and Vmax of the enzyme were calculated to be 100 µM and 1.47 µmole/min/µL, respectively. The equilibrium dissociation constant (Kd) of GTP binding with ARL15 was estimated to be about eight-fold higher than that of GDP. Small Angle X-ray Scattering (SAXS) data indicated that in solution, the apo state of monomeric ARL15 adopts a shape characterized by a globe of maximum linear dimension (Dmax) of 6.1 nm, and upon binding to GTP or GDP, the vector distribution profile changes to peak-n-tail shoulder with Dmax extended to 7.6 and 7.7 nm, respectively. Structure restoration using a sequence-based template and experimental SAXS data provided the first visual insight revealing that the folded N-terminal in the unbound state of the protein may toggle open upon binding to guanine nucleotides. The conformational dynamics observed in the N-terminal region offer a scope to develop drugs that target this unique GTPase, potentially providing treatments for a range of metabolic disorders.


Assuntos
Artrite Reumatoide , Doenças Metabólicas , Humanos , Nucleotídeos de Guanina , Nucleotídeos/metabolismo , Guanina , Espalhamento a Baixo Ângulo , Difração de Raios X , Fatores de Ribosilação do ADP/genética , Fatores de Ribosilação do ADP/metabolismo , Proteínas/metabolismo , Guanosina Trifosfato/metabolismo , Guanosina Difosfato
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