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1.
Int Immunopharmacol ; 133: 112091, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38657500

RESUMO

The pathophysiology of hepatic steatosis is thoroughly reviewed in this comprehensive report, with particular attention to the complex interactions between inflammatory pathways, insulin resistance, lipid metabolism, metabolic dysregulation, and immunological responses in the liver including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC). The study highlights the role of immune cell regulation in disease progression and explores the potential of immune cell-specific treatments for treating hepatic disorders. The development of liver disorders is significantly influenced by immune cells, including dendritic cells, T cells, and natural killer cells. Clinical investigations show that immune cell-specific treatments can effectively reduce liver fibrosis and inflammation. Future research should focus on finding new immunological targets for therapeutic interventions, as well as addressing the management challenges associated with NAFLD/NASH. Hepatic immune microorganisms also impact liver homeostasis and disorders. Improvements in immune cell regulation and liver transplantation methods give patients hope for better prognoses. Important phases include optimizing the selection of donors for malignancy of the liver, using machine perfusion for organ preservation, and fine-tuning immunosuppressive strategies. For focused treatments in hepatic steatosis, it is imperative to understand the intricate interactions between immune and metabolic variables. Understanding the liver's heterogeneous immune profile, encompassing a range of immune cell subpopulations, is crucial for formulating focused therapeutic interventions. To improve patient care and outcomes in hepatic illnesses, there is an urgent need for further research and innovation. Therefore, to effectively treat hepatic steatosis, it is important to enhance therapeutic techniques and maximize liver transplantation strategies.

2.
Clin Chim Acta ; 557: 117881, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38521163

RESUMO

In India, newborn screening (NBS) is essential for detecting health problems in infants. Despite significant progress, significant gaps and challenges persist. India has made great strides in genomics dueto the existence of the National Institute of Biomedical Genomics in West Bengal. The work emphasizes the challenges NBS programs confront with technology, budgetary constraints, insufficient counseling, inequality in illness panels, and a lack of awareness. Advancements in technology, such as genetic testing and next-generation sequencing, are expected to significantly transform the process. The integration of analytical tools, artificial intelligence, and machine learning algorithms could improve the efficiency of newborn screening programs, offering a personalized healthcare approach. It is critical to address gaps in information, inequities in illness incidence, budgetary restrictions, and inadequate counseling. Strengthening national NBS programs requires increased public awareness and coordinated efforts between state and central agencies. Quality control procedures must be used at every level for implementation to be successful. Additional studies endeavor to enhance NBS in India through public education, illness screening expansion, enhanced quality control, government incentive implementation, partnership promotion, and expert training. Improved neonatal health outcomes and the viability of the program across the country will depend heavily on new technology and counseling techniques.


Assuntos
Inteligência Artificial , Triagem Neonatal , Lactente , Recém-Nascido , Humanos , Triagem Neonatal/métodos , Testes Genéticos , Índia , Controle de Qualidade
3.
Indian J Anaesth ; 68(2): 129-141, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38435645

RESUMO

Background and Aims: Intrathecal bupivacaine is used for anaesthesia and analgesia but is associated with hypotension. Ropivacaine is an alternative drug that may have fewer cardiotoxic and neurotoxic events. This meta-analysis investigated whether intrathecal ropivacaine is associated with reduced hypotension as compared to bupivacaine. Methods: The meta-analysis is registered in the International Prospective Register of Systematic Reviews (PROSPERO). The databases PubMed, Cinahl Plus, Google Scholar, and Scopus were searched, and papers from January 1980 to January 2023 were deemed eligible and filtered using predetermined inclusion and exclusion criteria. The primary outcome was the incidence of hypotension. Secondary outcomes were the duration of sensory block, duration of motor block, incidence of bradycardia, ephedrine usage, and duration of analgesia. Jadad scores were used to evaluate the quality of the papers. RevMan statistical software® utilised inverse variance and a random effect model to calculate the standardised mean difference with 95% confidence intervals for continuous variables and the Mantel-Haenszel test and the random effect model to calculate the odds ratio for dichotomous variables. Results: Thirty-three papers, including 2475 patients in total, were included. The Jadad score was between 1 and 5. The incidence of hypotension was significantly higher with intrathecal bupivacaine than with ropivacaine (P = 0.02). The duration of sensory block (P < 0.001) and motor block (P < 0.001) was prolonged with intrathecal bupivacaine. The duration of analgesia favoured intrathecal bupivacaine (P = 0.003). Conclusion: Intrathecal ropivacaine has a reduced incidence of hypotension and a reduced duration of sensory block compared to bupivacaine.

4.
J Phys Chem B ; 128(8): 2010-2017, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38378451

RESUMO

The influence of the relative permittivity of the solvent medium on the single-chain dimension and flexibility of sodium polystyrenesulfonate chains has been investigated in mixed solvent media of methanol and water using viscosity experiments. Particular attention has been paid to explore the effect of the added low-molar-mass electrolyte. The root-mean-square (rms) radii of gyration of the chains in the unperturbed state have been calculated by applying the Flory model, while the intrinsic persistence lengths by the Benoit-Doty equation on the basis of the Kratky-Porod worm-like chain model. Estimation of the expansion factors for the rms radius of gyration, and the electrostatic persistence length helps evaluate the rms radii of gyration and the total persistence length of polystyrenesulfonate chains in the presence of varying amount of the supporting electrolyte. The polyion chains are highly extended at low ionic strengths but exhibit coil-like behavior with small persistence lengths when an excess of the supporting electrolyte is added in all the methanol-water mixtures investigated. Specifically, in the investigated solvent media, the polystyrenesulfonate chains have been found to shrink by ∼63-65% in the θ-state from their expanded conformation in the presence of 0.0001 mol L-1 NaCl. The chain dimensions pass through a maximum as the medium becomes richer in methanol, which could be explained by the formation and breakup of internal rings involving the polyion chain and water and/or methanol molecules. The intrinsic persistence length of sodium polystyrenesulfonate in a methanol-water mixture containing 0.1 mole fraction of methanol is ca. 1.3 times that in a medium with 0.3 mole fraction of methanol, indicating that flexibility of the polyion depends appreciably on the relative permittivity of the medium.

5.
Mol Biol Rep ; 51(1): 277, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319443

RESUMO

BACKGROUND: The most widely used food additive monosodium glutamate (MSG) has been linked to immunopathology. Conversely, quercetin (Q), a naturally occurring flavonoid has been demonstrated to have immunomodulatory functions. Therefore, the purpose of the study is to determine if quercetin can mitigate the deleterious effects of MSG on immune cells, and the possible involvement of TLR, if any.  METHODS AND RESULTS: This study was conducted on Q, to determine how it affects the inflammatory response triggered by MSG in primary cultured thymocytes and splenocytes from rats (n = 5). Q shielded cells by augmenting cell survival and decreasing lactate dehydrogenase leakage during MSG treatment. It decreased IL-1ß, IL-6, IL-8, and TNF-α expression and release by hindering NF-kB activation and by inhibiting the JAK/STAT pathway. Moreover, Q prevented NLRP3 activation, lowered IL-1ß production, and promoted an anti-inflammatory response by increasing IL-10 production. Q reduced MSG-induced cellular stress and inflammation by acting as an agonist for PPAR-γ and LXRα, preventing NF-kB activation, and lowering MMP-9 production via increasing TIMP-1. Additionally, Q neutralized free radicals, elevated intracellular antioxidants, and impeded RIPK3, which is involved in inflammation induced by oxidative stress, TNF-α, and TLR agonists in MSG-treated cells. Furthermore, it also modulated TYK2 and the JAK/STAT pathway, which exhibited an anti-inflammatory effect. CONCLUSIONS: MSG exposure is associated with immune cell dysfunction, inflammation, and oxidative stress, and Q modulates TLR to inhibit NF-kB and JAK/STAT pathways, providing therapeutic potential. Further research is warranted to understand Q's downstream effects and explore its potential clinical applications in inflammation.


Assuntos
NF-kappa B , Transdução de Sinais , Animais , Ratos , Anti-Inflamatórios , Inflamação/induzido quimicamente , Janus Quinases , Quercetina/farmacologia , Glutamato de Sódio/toxicidade , Baço , Fatores de Transcrição STAT , Timócitos , Fator de Necrose Tumoral alfa
6.
Phytomedicine ; 126: 155226, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387276

RESUMO

BACKGROUND: Chronic inflammation brought on by oxidative stress can result in several immunopathologies. Natural compounds with antioxidant characteristics, like quercetin, have shown effectiveness in reducing oxidative damage and regulating the immune response. PURPOSE: The commonly used food additive monosodium glutamate (M) causes immunosuppression by disrupting redox equilibrium and inducing oxidative stress. The goal of this work is to examine the therapeutic potential of quercetin against immunotoxicity brought on by M, revealing the molecular route implicated in such immunopathology by targeting the thymus and spleen, to support the development of future anti-inflammatory and antioxidant therapies. STUDY DESIGN AND METHODS: M-fed rats were employed as an immunotoxicity model and were supplemented with quercetin for four weeks. Hematological and biochemical parameters were measured; H&E staining, immunohistochemistry, flow cytometry, real-time quantitative PCR, and western blotting were performed. RESULTS: Based on the findings, TLR4 was activated by M to cause oxidative stress-mediated inflammation, which was alleviated by the supplementation of quercetin by modulating redox homeostasis to neutralize free radicals and suppress the inflammatory response. To prevent M-induced inflammation, quercetin demonstrated anti-inflammatory functions by blocking NF-kB activation, lowering the production of pro-inflammatory cytokines, and increasing the release of anti-inflammatory cytokines. By normalizing lipid profiles and lowering the potential risk of immunological deficiency caused by M, quercetin also improves lipid metabolism. Additionally, it has shown potential for modifying insulin levels, suggesting a possible function in controlling M-induced alteration in glucose metabolism. The addition of quercetin to M enhanced the immune response by improving immunoglobulin levels and CD4/CD8 expression in the thymus and spleen. Additionally, quercetin inhibited apoptosis by controlling mitochondrial caspase-mediated cellular signaling, suggesting that it may be able to halt cell death in M-fed rats. CONCLUSION: The results of this study first indicate that quercetin, via modulating redox-guided cellular signaling, has a promising role in reducing immune disturbances. This study illuminates the potential of quercetin as a safe, natural remedy for immunopathology caused by M, including thymic hypoplasia and/or splenomegaly, and paves the way for future anti-inflammatory and antioxidant supplements.


Assuntos
Antioxidantes , Quercetina , Ratos , Animais , Quercetina/farmacologia , Quercetina/uso terapêutico , Antioxidantes/metabolismo , Glutamato de Sódio/metabolismo , Glutamato de Sódio/farmacologia , Glutamato de Sódio/uso terapêutico , Baço , Oxirredução , Estresse Oxidativo , Inflamação/metabolismo , Terapia de Imunossupressão , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo
7.
Langmuir ; 40(10): 5314-5325, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38408899

RESUMO

Zwitterionic polymers are an emerging family of effective, low-fouling materials that can withstand unintended interactions with biological systems while exhibiting enhanced activity in bacterial matrix deterioration and biofilm eradication. Herein, we modularly synthesized an amphiphilic block copolymer, ZABCP, featuring potential bacteriostatic properties composed of a charge-switchable polyzwitterionic segment and a redox-sensitive pendant disulfide-labeled polymethacrylate block. The leucine-appended polyzwitterionic segment with alternatively positioned cationic amine and anionic carboxylate functionalities undergoes charge alterations (+ve → 0 → -ve) on pH variation. By introducing appropriate amphiphilicity, ZABCP forms distinct vesicles with redox-sensitive bilayer membranes and zwitterionic shielding coronas, enabling switching of surface charge. ZABCP vesicles exhibit 180 ± 20 nm hydrodynamic diameter, and its charge switching behavior in response to pH was confirmed by the change of zeta potential value from -23 to +36 mV. The binding interaction between ZABCP vesicles with lysozyme and pepsin proteins strengthens when the surface charge shifts from neutral (pH 7.4) to either anionic or cationic. This surface-charge-switchable phenomenon paves the way for implementing cationic ZABCP vesicles for bacterial cell growth inhibition, which is shown by the pronounced transition of cellular morphology, including clustering, aggregation, or elongation as well as membrane disruption for both Bacillus subtilis (Gram-positive) and Escherichia coli (Gram-negative). Such enhanced bacteriostatic activity could be ascribed to a strong electrostatic interaction between cationic vesicles and negatively charged bacterial membranes, leading to cell membrane disruption. Overall, this study provides a tailor-made approach to adopt low-fouling properties and potential bacteriostatic activity using zwitterionic polymers through precise control of pH.


Assuntos
Incrustação Biológica , Incrustação Biológica/prevenção & controle , Proteínas/metabolismo , Cátions/química , Membrana Celular/metabolismo , Polímeros/química , Propriedades de Superfície
8.
ACS Appl Bio Mater ; 7(1): 144-153, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38150303

RESUMO

Cell migration is an essential dynamic process for most living cells, mainly driven by the reorganization of actin cytoskeleton. To control actin dynamics, a molecular architecture that can serve as a nucleator has been designed by polymerizing sulfobetaine methacrylate. The synthesized zwitterionic polymer, poly(sulfobetaine methacrylate) (PZI), effectively nucleates the polymerization process of G-actin and substantially accelerates the rate of polymerization. Isothermal titration calorimetry (ITC) and bioinformatics analysis indicated binding between PZI and monomeric G-actin. Thus, in vitro actin dynamics was studied by dynamic light scattering (DLS), pyrene-actin polymerization assay, and total internal reflection fluorescence microscopy (TIRFM). Furthermore, a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophore-containing monomeric unit was incorporated into the sulfobetaine zwitterionic architecture to visualize the effect of polymer in the cellular environment. The BODIPY-containing zwitterionic sulfobetaine polymer (PZI-F) successfully penetrated the cell and remained in the lysosome with minimal cytotoxicity. Confocal microscopy revealed the influence of this polymer on the cellular actin cytoskeleton dynamics. The PZI-F polymer was successfully able to inhibit the collective migration of the human cervical cancer cell line (HeLa cell) and breast cancer cell line (MDA-MB-231 cell), as confirmed by a wound healing assay. Therefore, polyzwitterionic sulfobetaine could be explored as an inhibitor of cancer cell migration.


Assuntos
Actinas , Betaína/análogos & derivados , Compostos de Boro , Neoplasias , Humanos , Actinas/metabolismo , Células HeLa , Citoesqueleto de Actina/metabolismo , Movimento Celular
9.
Nanoscale ; 15(45): 18212-18217, 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37933179

RESUMO

Herein, we investigate the bioactivity of small extracellular vesicles (sEVs), focusing on their local effect in the brain. sEVs from mononuclear cells (MNCs) showed superior effects in vitro to sEVs from mesenchymal stem cells (MSCs) and were able to promote neuroprotection and decrease microglia reactivity in a stroke mouse model.


Assuntos
Vesículas Extracelulares , Acidente Vascular Cerebral , Animais , Camundongos , Microglia , Neuroproteção , Encéfalo , Acidente Vascular Cerebral/terapia , Modelos Animais de Doenças
10.
J Enzyme Inhib Med Chem ; 38(1): 2276665, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37919954

RESUMO

Structural tailoring of the flavone framework (position 7) via organopalladium-catalyzed C-C bond formation was attempted in this study. The impact of substituents with varied electronic effects (phenyl ring, position 2 of the benzopyran scaffold) on the antitumor properties was also assessed. Resultantly, the efforts yielded a furyl arm bearing benzopyran possessing a 4-fluoro phenyl ring (position 2) (14) that manifested a magnificent antitumor profile against the Ishikawa cell lines mediated through dual inhibition of PARP and tubulin [(IC50 (PARP1) = 74 nM, IC50 (PARP2) = 109 nM) and tubulin (IC50 = 1.4 µM)]. Further investigations confirmed the ability of 14 to induce apoptosis as well as autophagy and cause cell cycle arrest at the G2/M phase. Overall, the outcome of the study culminated in a tractable dual PARP-tubulin inhibitor endowed with an impressive activity profile against endometrial cancer.


Assuntos
Antineoplásicos , Neoplasias do Endométrio , Flavonas , Humanos , Feminino , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/química , Tubulina (Proteína)/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/farmacologia , Antineoplásicos/química , Apoptose , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Flavonas/farmacologia , Benzopiranos , Proliferação de Células
11.
Environ Monit Assess ; 195(10): 1250, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37758966

RESUMO

The present work was conducted in the forest-based ecosystem of Chhattisgarh in order to assess the varietal performance of coffee varieties along with silver oak in terms of growth, biomass, and carbon dynamics. Five coffee varieties were planted in silver oak shade in a randomized block design with four replications. The aim of the present investigation is to assess the economic and ecological feasibility of forest-based coffee plantations in the Bastar region of Chhattisgarh. Findings reflect the maximum under-storied plant height in Chandragiri Dwarf (1.85 m) which was at par with CxR (1.82 m) and San Ramon (1.71 m). The maximum above and below-ground carbon stock (48.40 and 12.09 Mg ha-1, respectively), as well as carbon dioxide (CO2) mitigation (177.63 and 44.41 Mg ha-1, respectively) from the under-storied coffee plantation, was recorded in CxR. In the upper-storied plantation, the above and below-ground biomass of silver oak recorded the maximum carbon stock (201.24 and 50.31 Mg ha-1, respectively) and CO2 mitigation (738.54 and 184.63 Mg ha-1) in S-8 intercropped lines. The highest value of carbon credit was recorded under the coffee variety S-8 and silver oak agroecosystem. The S-8, CxR, and Chandragiri Dwarf varieties performed quite well in terms of the expected value of carbon credit.


Assuntos
Dióxido de Carbono , Ecossistema , Biomassa , Prata , Monitoramento Ambiental , Florestas , Plantas , Índia , Árvores , Solo
12.
Int J Biol Macromol ; 253(Pt 5): 126977, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37739287

RESUMO

The major drawback associated with petroleum-based polymer products is pollution, leading to environmental hazards. Biodegradable polymers and biocomposites have the potential to play a major role in replacing the conventional polymers in specific applications on a case to case basis. In the current study, sawdust reinforced polylactic acid/polycaprolactone (PLA/PCL) biocomposites were developed using the melt extrusion technique. Primary processed fine sawdust was reinforced with PLA/PCL blend in a mini twin screw extruder in different weight fractions (10 %, 20 %, 30 %, and 40 %). The developed biocomposites were subjected to tensile testing, which indicated that the increased weight percent of sawdust reduced the tensile strength. The materials were further characterized, using sophisticated analytical such as field emission scanning electron microscopy, differential scanning calorimetry and thermogravimetry analysis. The composite containing 30 % sawdust concentration presented the best results with tensile strength of 26.5 MPa, tensile strain of 4.4 % and onset degradation temperature of 320 °C. The same formulation was successfully scaled up to the pilot level of 5 kg batch. It was further subjected to secondary processing to produce market ready cutlery items. Biodegradability studies in simulated composting environments revealed that addition of sawdust drastically reduces the lag phase in degradation and total degradation may be obtained in approximately 90 days. Based on the investigation, there is optimism that the PLA/PCL composites, blended with sawdust may ensure commercial application of sustainable polymer blends at affordable prices.


Assuntos
Poliésteres , Polímeros , Poliésteres/química , Polímeros/química , Resistência à Tração
13.
Indian J Anaesth ; 67(7): 579-589, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37601928

RESUMO

Background and Aims: Thyroid surgery is moderately painful, and many techniques to reduce postoperative pain have been studied. Regional techniques are a part of multimodal analgesia employed for various surgical cases. Bilateral superficial cervical plexus block (BSCPB) is a commonly used regional anaesthesia technique for analgesia for thyroid surgery. A previous meta-analysis by this group had left questions about some facets of the technique, to which further trials have contributed. Methods: The systematic review and meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO) CRD42022315499. It is an update to a previously published paper in 2018. An updated systematic search, critical appraisal, and analysis of clinical trials were performed. Trials investigating preoperative or postoperative BSCPB compared to control in patients undergoing thyroid surgery were included in the search. The primary outcome was postoperative opioid consumption. The secondary outcomes were the duration of analgesia (time to request of analgesia), Visual Analogue Scale (VAS) pain scores at 0, 4, 12, and 24 h, postoperatively, rates of postoperative nausea and vomiting (PONV), postoperative rescue analgesic consumption, and intraoperative morphine use. Results: A total of 31 studies and 2,273 patients were included in this analysis. BSCPB significantly reduced post-thyroidectomy opioid consumption (P < 0.001). Additionally, the duration of analgesia was prolonged following BSCPB. VAS scores for 24 h (postoperatively), intraoperative morphine use, and rescue analgesia (postoperatively) remained significantly lower in patients who received BSCPB. There was also a statistically significant reduction in PONV (P = 0.02). Conclusion: BSCPB offers superior postoperative analgesia with a reduction in opioid use, reduction in PONV, and improvement in VAS scores.

14.
J Control Release ; 360: 549-563, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37406818

RESUMO

Extracellular vesicles (EVs) work as communication vehicles, allowing the exchange of bioactive molecules (microRNAs, mRNAs, proteins, etc) between neighbouring and distant cells in the organism. EVs are thus important players in several physiological and pathological processes. Thus, it is critical to understand their role in cellular/organ communication to fully evaluate their biological, diagnosis and therapeutic potential. In addition, recent studies have explored the controlled release of EVs for regenerative medicine applications and thus the evaluation of their release profile is important to correlate with biological activity. Here, we give a brief introduction about EV imaging platforms in terms of their sensitivity, penetration depth, cost, and operational simplicity, followed by a discussion of different EV labelling processes with their advantages and limitations. Next, we cover the relevance of these imaging platforms to dissect the tropism and biological role of endogenous EVs. We also cover the relevance of imaging platforms to monitor the accumulation of exogenous EVs and their potential cellular targets. Finally, we highlight the importance of imaging platforms to investigate the release profile of EVs from different controlled systems.


Assuntos
Vesículas Extracelulares , MicroRNAs , Distribuição Tecidual , Preparações de Ação Retardada/metabolismo , Vesículas Extracelulares/metabolismo , MicroRNAs/metabolismo , Comunicação Celular
15.
Front Endocrinol (Lausanne) ; 14: 1110572, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124741

RESUMO

Spermatogenesis is a multi-step process of male germ cell (Gc) division and differentiation which occurs in the seminiferous tubules of the testes under the regulation of gonadotropins - Follicle Stimulating Hormone (FSH) and Luteinising hormone (LH). It is a highly coordinated event regulated by the surrounding somatic testicular cells such as the Sertoli cells (Sc), Leydig cells (Lc), and Peritubular myoid cells (PTc). FSH targets Sc and supports the expansion and differentiation of pre-meiotic Gc, whereas, LH operates via Lc to produce Testosterone (T), the testicular androgen. T acts on all somatic cells e.g.- Lc, PTc and Sc, and promotes the blood-testis barrier (BTB) formation, completion of Gc meiosis, and spermiation. Studies with hypophysectomised or chemically ablated animal models and hypogonadal (hpg) mice supplemented with gonadotropins to genetically manipulated mouse models have revealed the selective and synergistic role(s) of hormones in regulating male fertility. We here have briefly summarized the present concept of hormonal control of spermatogenesis in rodents and primates. We also have highlighted some of the key critical questions yet to be answered in the field of male reproductive health which might have potential implications for infertility and contraceptive research in the future.


Assuntos
Espermatogênese , Testículo , Masculino , Camundongos , Animais , Espermatogênese/fisiologia , Células de Sertoli/fisiologia , Gonadotropinas , Hormônio Foliculoestimulante/fisiologia , Hormônio Luteinizante , Mamíferos
16.
Entropy (Basel) ; 25(3)2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36981429

RESUMO

Recent advances in quantum hardware offer new approaches to solve various optimization problems that can be computationally expensive when classical algorithms are employed. We propose a hybrid quantum-classical algorithm to solve a dynamic asset allocation problem where a target return and a target risk metric (expected shortfall) are specified. We propose an iterative algorithm that treats the target return as a constraint in a Markowitz portfolio optimization model, and dynamically adjusts the target return to satisfy the targeted expected shortfall. The Markowitz optimization is formulated as a Quadratic Unconstrained Binary Optimization (QUBO) problem. The use of the expected shortfall risk metric enables the modeling of extreme market events. We compare the results from D-Wave's 2000Q and Advantage quantum annealers using real-world financial data. Both quantum annealers are able to generate portfolios with more than 80% of the return of the classical optimal solutions, while satisfying the expected shortfall. We observe that experiments on assets with higher correlations tend to perform better, which may help to design practical quantum applications in the near term.

17.
Aust J Rural Health ; 31(3): 464-470, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36745537

RESUMO

OBJECTIVE: Perioperative initiation of opioids continues to be a major contributor to chronic use, misuse and diversion in regional areas. There is considerable effort to mitigate harm through avoiding excessive prescribing and reducing the risk of persistent postoperative opioid use. Improving perioperative documentation practices has been reported to ensure appropriate opioid initiation and de-escalation. It has not been established whether these strategies are utilised in regional hospitals. METHODS: A retrospective observational study of perioperative opioid prescribing and documentation practices in Goulburn Base Hospital, a regional centre in the Southern New South Wales (NSW) Local Health District. Data were collected from 110 records and validated for adult patients undergoing elective total knee replacement (TKR) or total hip replacement (THR) from 12 January 2020 to 13 January 2021. OUTCOME MEASURES: To observe perioperative opioid prescribing and utilisation of harm reduction strategies in a regional hospital. RESULTS: 65% of patients were opioid naïve (ON). Preoperative pain assessments and patient education were completed in 23% and 15% of records, respectively. Postoperative opioids were prescribed for 99% of patients, with 74% prescribed a slow-release (SR) formulation. 50% of patients were discharged with an SR prescription. Inadequate postoperative pain control was reported in 21% of patients. Of the 103 patients prescribed opioids on discharge, only 20% included a de-escalation plan and only 35% of discharge summaries included dose and quantity of opioids supplies. CONCLUSIONS: This study has identified underutilisation of perioperative harm reduction strategies despite the potential to improve appropriate initiation and de-escalation of opioids. These findings highlight opportunities for improvement in regional hospitals.


Assuntos
Analgésicos Opioides , Redução do Dano , Adulto , Humanos , Analgésicos Opioides/uso terapêutico , New South Wales , Dor Pós-Operatória/tratamento farmacológico , Padrões de Prática Médica , Estudos Retrospectivos
18.
Nat Mater ; 22(1): 36-41, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36396962

RESUMO

The honeycomb magnet α-RuCl3 has attracted considerable interest because it is proximate to the Kitaev Hamiltonian whose excitations are Majoranas and vortices. The thermal Hall conductivity κxy of Majorana fermions is predicted to be half-quantized. Half-quantization of κxy/T (T, temperature) was recently reported, but this observation has proven difficult to reproduce. Here, we report detailed measurements of κxy on α-RuCl3 with the magnetic field B ∥ a (zigzag axis). In our experiment, κxy/T is observed to be strongly temperature dependent between 0.5 and 10 K. We show that its temperature profile matches the distinct form expected for topological bosonic modes in a Chern-insulator-like model. Our analysis yields magnon band energies in agreement with spectroscopic experiments. At high B, the spin excitations evolve into magnon-like modes with a Chern number of ~1. The bosonic character is incompatible with half-quantization of κxy/T.

19.
Philos Trans A Math Phys Eng Sci ; 381(2241): 20210414, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36463920

RESUMO

Novel magnetic materials are important for future technological advances. Theoretical and numerical calculations of ground-state properties are essential in understanding these materials, however, computational complexity limits conventional methods for studying these states. Here we investigate an alternative approach to preparing materials ground states using the quantum approximate optimization algorithm (QAOA) on near-term quantum computers. We study classical Ising spin models on unit cells of square, Shastry-Sutherland and triangular lattices, with varying field amplitudes and couplings in the material Hamiltonian. We find relationships between the theoretical QAOA success probability and the structure of the ground state, indicating that only a modest number of measurements ([Formula: see text]) are needed to find the ground state of our nine-spin Hamiltonians, even for parameters leading to frustrated magnetism. We further demonstrate the approach in calculations on a trapped-ion quantum computer and succeed in recovering each ground state of the Shastry-Sutherland unit cell with probabilities close to ideal theoretical values. The results demonstrate the viability of QAOA for materials ground state preparation in the frustrated Ising limit, giving important first steps towards larger sizes and more complex Hamiltonians where quantum computational advantage may prove essential in developing a systematic understanding of novel materials. This article is part of the theme issue 'Quantum annealing and computation: challenges and perspectives'.

20.
J Exp Zool A Ecol Integr Physiol ; 339(2): 193-209, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36336790

RESUMO

Gonadotropin-releasing hormone (GnRH) is the primary regulator of the mammalian reproductive axis. We investigated the spatiotemporal expression of GnRH splice variants (V1, V2, and V3) and splicing factors (Srsf7, Srsf9, and Tra-2) in the male mice brain. Further, using in silico tools, we predicted protein structure and the reason for the low translational efficiency of V2 and V3. Messenger RNA levels of GnRH variants and splicing factors were quantified using real-time reverse transcription-polymerase chain reaction at different age groups. Our data show that expression of almost all the variants alters with aging in all the brain regions studied; even in comparison to the hypothalamus, several brain areas were found to have higher expression of these variants. Hypothalamic expression of splicing factors such as Srsf7, Srsf9, and Tra-2 also change with aging. Computational studies have translation repressors site on the V3, which probably reduces its translation efficiency. Also, V2 is an intrinsically disordered protein that might have a regulatory or signaling function. In conclusion, this study provides novel crucial information and multiple starting points for future analysis of GnRH splice variants in the brain.


Assuntos
Hormônio Liberador de Gonadotropina , Hipotálamo , Camundongos , Masculino , Animais , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/fisiologia , Reprodução , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Mamíferos/metabolismo , Fatores de Processamento de RNA/metabolismo
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