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1.
EMBO J ; 43(2): 225-249, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38177503

RESUMEN

Respiratory complex I (NADH:ubiquinone oxidoreductase) is essential for cellular energy production and NAD+ homeostasis. Complex I mutations cause neuromuscular, mitochondrial diseases, such as Leigh Syndrome, but their molecular-level consequences remain poorly understood. Here, we use a popular complex I-linked mitochondrial disease model, the ndufs4-/- mouse, to define the structural, biochemical, and functional consequences of the absence of subunit NDUFS4. Cryo-EM analyses of the complex I from ndufs4-/- mouse hearts revealed a loose association of the NADH-dehydrogenase module, and discrete classes containing either assembly factor NDUFAF2 or subunit NDUFS6. Subunit NDUFA12, which replaces its paralogue NDUFAF2 in mature complex I, is absent from all classes, compounding the deletion of NDUFS4 and preventing maturation of an NDUFS4-free enzyme. We propose that NDUFAF2 recruits the NADH-dehydrogenase module during assembly of the complex. Taken together, the findings provide new molecular-level understanding of the ndufs4-/- mouse model and complex I-linked mitochondrial disease.


Asunto(s)
Enfermedad de Leigh , Enfermedades Mitocondriales , Animales , Ratones , Complejo I de Transporte de Electrón/genética , Complejo I de Transporte de Electrón/metabolismo , Enfermedad de Leigh/genética , Mitocondrias/metabolismo , Enfermedades Mitocondriales/genética , NAD/metabolismo , NADH Deshidrogenasa/genética , NADH Deshidrogenasa/metabolismo
2.
BMC Cancer ; 24(1): 131, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38273265

RESUMEN

BACKGROUND: Current guidelines advocate for colorectal cancer (CRC) screening in adults who are at risk by using direct visualization methods such as colonoscopy. However, in Egypt, there is a paucity of data regarding the current practice of colonoscopy screening. Moreover, more information is needed about the knowledge and attitudes of potential participants regarding the procedure and possible barriers that can limit their participation. METHODS: We conducted a nationwide cross-sectional study using an interview-based survey of patients aged 45 years or above who presented to outpatient clinics of nine university hospitals throughout Egypt. Participants were surveyed to assess their compliance with CRC colonoscopy screening guidelines, their knowledge of and attitude towards colonoscopy screening, and their perspective on potential barriers to colonoscopy screening. RESULTS: A total of 1,453 participants responded to our survey in the nine study centers. Only a minority of participants (2.3%) were referred for CRC screening. Referral rates were higher among those who knew someone with a history of CRC (5.3% vs 1.5%, p < 0.001) or had a discussion with their physician about CRC (25.8% vs 0.7%, p < 0.001). Few responders (3.2%) had good knowledge regarding CRC screening. After introducing the concept of CRC screening to all participants, most patients (66.7%) showed a positive attitude towards having the procedure. Financial burden and fear of results were the two most frequently cited barriers to undergoing CRC screening (81.1%; and 60.1%, respecteively). CONCLUSIONS: Despite the positive attitude, there is insufficient knowledge about CRC screening among eligible participants in Egypt. This has probably contributed to low compliance with current CRC screening guidelines and needs to be addressed at the national level.


Asunto(s)
Neoplasias Colorrectales , Conocimientos, Actitudes y Práctica en Salud , Adulto , Humanos , Estudios Transversales , Egipto/epidemiología , Detección Precoz del Cáncer/métodos , Tamizaje Masivo/métodos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/prevención & control , Colonoscopía
3.
J Biol Chem ; 298(3): 101602, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35063503

RESUMEN

Mitochondrial complex I (NADH:ubiquinone oxidoreductase), a crucial enzyme in energy metabolism, captures the redox potential energy from NADH oxidation/ubiquinone reduction to create the proton motive force used to drive ATP synthesis in oxidative phosphorylation. High-resolution single-particle electron cryo-EM analyses have provided detailed structural knowledge of the catalytic machinery of complex I, but not of the molecular principles of its energy transduction mechanism. Although ubiquinone is considered to bind in a long channel at the interface of the membrane-embedded and hydrophilic domains, with channel residues likely involved in coupling substrate reduction to proton translocation, no structures with the channel fully occupied have yet been described. Here, we report the structure (determined by cryo-EM) of mouse complex I with a tight-binding natural product acetogenin inhibitor, which resembles the native substrate, bound along the full length of the expected ubiquinone-binding channel. Our structure reveals the mode of acetogenin binding and the molecular basis for structure-activity relationships within the acetogenin family. It also shows that acetogenins are such potent inhibitors because they are highly hydrophobic molecules that contain two specific hydrophilic moieties spaced to lock into two hydrophilic regions of the otherwise hydrophobic channel. The central hydrophilic section of the channel does not favor binding of the isoprenoid chain when the native substrate is fully bound but stabilizes the ubiquinone/ubiquinol headgroup as it transits to/from the active site. Therefore, the amphipathic nature of the channel supports both tight binding of the amphipathic inhibitor and rapid exchange of the ubiquinone/ubiquinol substrate and product.


Asunto(s)
Acetogeninas , Complejo I de Transporte de Electrón , Acetogeninas/antagonistas & inhibidores , Acetogeninas/metabolismo , Acetogeninas/farmacología , Animales , Microscopía por Crioelectrón , Complejo I de Transporte de Electrón/metabolismo , Ratones , NAD/metabolismo , Oxidación-Reducción , Relación Estructura-Actividad , Ubiquinona/metabolismo
4.
Waste Manag Res ; 41(2): 467-476, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36128600

RESUMEN

A smart energy recovery process can achieve maximum energy recovery from organic wastes. Pretreatment of feedstock is essential to biogas and methane yields during the anaerobic digestion process. This work combined particle size reduction with Fe3O4 nanoparticles to investigate their influence on biogas and methane yields from anaerobic digestion of Arachis hypogea shells. Twenty milligrams per litre of Fe3O4 nanoparticles was implemented with 2, 4, 6 and 8 mm particle sizes and a single treatment of Fe3O4 for 35 days. The treatments were compared with each other and were discovered to significantly (p < 0.05) enhance biogas yield by 37.40%, 50.10%, 54.40%, 51.40% and 35.50% compared with control, respectively. Specific biogas yield recorded was 966.2, 1406, 1552.7, 1317.4, 766.2 and 413 mL g-1 volatile solid. This study showed the combination of Fe3O4 with 6 mm particle size of Arachis hypogea shells produced the optimum biogas and methane yields. The addition of Fe3O4 to particle sizes below 6 mm resulted in over-accumulation of volatile fatty acids and lowered the gas yield. This can be applied on an industrial scale.


Asunto(s)
Arachis , Biocombustibles , Tamaño de la Partícula , Metano , Industrias , Anaerobiosis , Reactores Biológicos
5.
Waste Manag Res ; 40(8): 1176-1188, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35075967

RESUMEN

Optimising biogas yields from anaerobic digestion of organic wastes is significant to maximum energy recovery in the biodigestion process and has become an important topic of interest. Substrate particle size is an important process parameter in biogas production, and it precedes other pretreatments methods for the majority of the lignocellulose materials. Optimisation of biogas yield using Response Surface Methodology (RSM) was done, and temperature, hydraulic retention time and particle size were considered variables to develop the predictive models. Pretreatment of groundnut shells was investigated using particle size reduction of mechanical pretreatment methods. After pretreatment, 30 samples were digested in a batch digester at mesophilic temperature. The experimental results showed that the temperature, hydraulic retention time and particle size had significant effects of interaction (p < 0.05). The optimum experimental and predicted yields are: 44.70 and 42.92 (lNkgoDM) organic dry matter biogas yield, 20.80 and 19.09 (lN/kgFM) fresh mass biogas yield, 24.00 and 22.68 (lNCH4oDM) organic dry methane yield and 12.30 and 15.59 (lNCH4FM) fresh mass methane yield, respectively. The R2 recorded for the four yield components were 0.6268, 0.5875, 0.6109 and 0.5547. These values seem to be lower and a sign of the average fit of the model. Biogas production from groundnut shells was significantly improved with statistical optimisation and the pretreatment method.


Asunto(s)
Biocombustibles , Metano , Anaerobiosis , Reactores Biológicos , Tamaño de la Partícula , Temperatura
6.
Opt Lett ; 42(9): 1788-1791, 2017 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-28454161

RESUMEN

We study an optical transistor (switch and amplifier) and router by spontaneous parametric four-wave mixing and fluorescence in diamond nitrogen-vacancy (NV) center. The routing results from three peaks of fluorescence signal in the time domain, while the switching and amplification are realized by correlation and squeezing. The intensity switching speed is about 17 ns. The optical transistor and router are controlled by the power of incident beams. Our experimental results provide that the advance technique of peak division and channel equalization ratio of about 90% are applicable to all optical switching and routing.

7.
Phys Chem Chem Phys ; 19(23): 15059-15066, 2017 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-28561103

RESUMEN

We realized an optical transistor and router utilizing multi-order fluorescence and spontaneous parametric four-wave mixing. Specifically, the optical routing action was derived from the results of splitting in the intensity signal due to a dressing effect, whereas the transistor as a switch and amplifier was realized by a switching correlation and squeezing via a nonlinear phase. A substantial enhancement of the optical contrast was observed for switching applications using correlation and squeezing contrary to the intensity signal. Moreover, the controlling parameters were also configured to devise a control mechanism for the optical transistor and router.

8.
BMC Biol ; 14: 65, 2016 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-27506389

RESUMEN

BACKGROUND: The biguanides are a family of drugs with diverse clinical applications. Metformin, a widely used anti-hyperglycemic biguanide, suppresses mitochondrial respiration by inhibiting respiratory complex I. Phenformin, a related anti-hyperglycemic biguanide, also inhibits respiration, but proguanil, which is widely used for the prevention of malaria, does not. The molecular structures of phenformin and proguanil are closely related and both inhibit isolated complex I. Proguanil does not inhibit respiration in cells and mitochondria because it is unable to access complex I. The molecular features that determine which biguanides accumulate in mitochondria, enabling them to inhibit complex I in vivo, are not known. RESULTS: Here, a family of seven biguanides are used to reveal the molecular features that determine why phenformin enters mitochondria and inhibits respiration whereas proguanil does not. All seven biguanides inhibit isolated complex I, but only four of them inhibit respiration in cells and mitochondria. Direct conjugation of a phenyl group and bis-substitution of the biguanide moiety prevent uptake into mitochondria, irrespective of the compound hydrophobicity. This high selectivity suggests that biguanide uptake into mitochondria is protein mediated, and is not by passive diffusion. Only those biguanides that enter mitochondria and inhibit complex I activate AMP kinase, strengthening links between complex I and the downstream effects of biguanide treatments. CONCLUSIONS: Biguanides inhibit mitochondrial complex I, but specific molecular features control the uptake of substituted biguanides into mitochondria, so only some biguanides inhibit mitochondrial respiration in vivo. Biguanides with restricted intracellular access may be used to determine physiologically relevant targets of biguanide action, and for the rational design of substituted biguanides for diverse clinical applications.


Asunto(s)
Adenilato Quinasa/metabolismo , Biguanidas/química , Biguanidas/farmacología , Complejo I de Transporte de Electrón/metabolismo , Animales , Bovinos , Línea Celular Tumoral , Permeabilidad de la Membrana Celular/efectos de los fármacos , Respiración de la Célula/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Membranas Mitocondriales/efectos de los fármacos , Membranas Mitocondriales/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Fenformina/farmacología , Ratas , Rotenona/farmacología , Solubilidad
9.
Indian J Biochem Biophys ; 51(1): 52-7, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24791417

RESUMEN

During the complete oxidation of fatty acids, the electrons removed from fatty acids in different forms (FADH2 and NADH2) pass through the respiratory chain, driving the ATP synthesis. Generally, the ATP yield due to the complete oxidation of fatty acids is calculated by sum total the ATPs obtained due to the oxidation of FADH2 and NADH2 due to lack of any particular method. This calculation is simple for saturated even numbered fatty acids, but in the case of saturated and unsaturated odd numbered fatty acids the calculation of ATP yield is difficult and needs mathematical calculations due to some changes in their beta-oxidation pathway when compared to the pathway of saturated even numbered fatty acids. These calculations are made simple by our derivations and following formulae where we require only number of carbon atoms and double bonds present in a fatty acid. Our method is superior and easier in comparison to long mathematical calculations that are in the practice.


Asunto(s)
Adenosina Trifosfato/biosíntesis , Ácidos Grasos Insaturados/metabolismo , Ácidos Grasos/metabolismo , Modelos Biológicos , Ácidos Grasos/química , Ácidos Grasos Insaturados/química , Oxidación-Reducción
10.
Transplant Cell Ther ; 30(5): 512.e1-512.e15, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38365082

RESUMEN

Young adults from underserved racial/ethnic groups are critically needed as unrelated hematopoietic stem cell (HSC) donors, yet they are more likely than other groups to opt out of donation after having matched a patient. Understanding which factors are most strongly associated with opting out among young underserved racial/ ethnic registered donors compared with their White counterparts will provide the basis for specific interventions to improve donor retention. We sought to determine the key, modifiable psychosocial, registry-related, and donation-related characteristics that are uniquely associated with opting out across 5 key racial/ethnic groups of young HSC donor registry members who had been contacted as a potential match for a patient. This study examines data from a large cross-sectional survey of young (age 18 to 30) registry members shortly after they preliminarily matched a patient (CT-stage) and continued toward or opted out of donation (CT-C and CT-NI), stratified by racial/ethnic group and sex. We assessed psychosocial, registry-related, and donation-related characteristics for all participants. We used chi-squared and F tests to assess differences between racial/ethnic groups. A separate logistic regression analysis for each racial/ethnic group was conducted to quantify adjusted associations between each variable and opting out. Then, we compared these associations across the racial/ethnic groups by evaluating the interaction effect between each variable and racial/ethnic group, with the same outcome (CT-C versus CT-NI) in question. Nine hundred thirty-five participants were surveyed, including 284 White, 165 Hispanic, 191 Black, 192 Asian/Pacific Islander, and 103 Multiracial/multiethnic participants. There were significant differences across racial/ethnic groups in values/goals, religious objections to donation, HSC-related medical mistrust, and parental involvement in donation decisions. Adjusted logistic regression subgroup analyses indicated that ambivalence was strongly associated with opting out across all racial/ethnic groups. Greater focus on intrinsic life goals (e.g., raising a family, becoming a community leader, influencing social values) was associated with opting out in the Multiracial/multiethnic, Hispanic, and Asian/Pacific Islander groups. Healthcare mistrust and insufficient registry contact was a significant factor for Hispanic participants. Protective factors against opting out included remembering joining the registry (Black participants), and parental support for donation decision (Asian/Pacific Islander participants). The performance of each logistic regression model was strong, with area-under-the curve ≥.88, CT-stage outcome classification accuracy ≥89%, and good fit between expected and observed opt-out probabilities. In the analysis across different racial/ethnic groups, the only significant interaction was race/ethnicity by whether more contact with the registry would have changed the decision at CT-stage; this variable was significant only for the Hispanic group. In the within-group analysis for Hispanic participants, the "more registry contact" variable was strongly associated with opting out (odds ratio 5.8, P = .03). Consistent with a growing body of HSC donor research, ambivalence was a key factor associated with opting-out for all racial/ethnic groups. Other key variables were differentially associated with opting-out depending on racial/ethnic group. Our study highlights key variables that registries should focus on as they develop targeted and tailored strategies to enhance commitment and reduce attrition of potential donors.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Sistema de Registros , Adolescente , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Estudios Transversales , Etnicidad/estadística & datos numéricos , Etnicidad/psicología , Trasplante de Células Madre Hematopoyéticas/psicología , Células Madre Hematopoyéticas , Grupos Raciales/estadística & datos numéricos , Grupos Raciales/psicología , Estados Unidos , Donante no Emparentado , Blanco , Hispánicos o Latinos , Negro o Afroamericano , Asiático Americano Nativo Hawáiano y de las Islas del Pacífico
11.
J Ayub Med Coll Abbottabad ; 25(1-2): 162-4, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-25098085

RESUMEN

BACKGROUND: Electrolyte derangements are common sequel of traumatic brain injury. Use of intravenous fluids, diuretics, syndrome of inappropriate ADH secretion and cerebral salt washing are some of the factors responsible for this. Proper in time detection followed by appropriate treatment not only improves neurological status but also decrease morbidity and mortality. This study was conducted to know serum derangements of different electrolytes in patients with traumatic brain injury. METHODOLOGY: This cross-sectional study was conducted in Pakistan Institute of Medical Sciences. Islamabad, Pakistan from Feb 2009 to Feb 2010. All adult patients with traumatic brain injury who presented to Neurosurgical department with severe head injury (GCS < 8) and who need monitoring in high dependency unit, were included in this study. Initially twice daily serum electrolyte monitoring for one week then once daily for remaining period of hospital stay was carried out. All samples were sent to Pathology department of Pakistan Institute of Medical Sciences, Islamabad. Patients who need corrective measures for imbalance had repetition of sampling after giving appropriate therapy. Statistical analysis was performed on SPSS-16. RESULTS: Total 215 patients presented with severe head injury that were managed in high dependency unit. Out of which 127 (59.1%) were male and 88 (40.9%) were females. Most of them were adults between 21-40) years of age (21.4%; 24.7%). Sodium was the main electrolyte that underwent change & out of which hyper-natremia was major abnormality that occurred in 140 (65.1%) of patients. This is followed by hypo-kalemia that occurred in 79 (36.7%) of patients. Serum calcium & magnesium levels show little derangements. CONCLUSION: Electrolyte imbalance following traumatic head injury is an important cause to look for in patient monitoring. Sodium is the chief electrolytes of concern. Serum potassium and calcium levels also under goes notable changes.


Asunto(s)
Lesiones Encefálicas/sangre , Potasio/sangre , Sodio/sangre , Adulto , Calcio/sangre , Estudios Transversales , Femenino , Humanos , Magnesio/sangre , Masculino , Adulto Joven
12.
Surg Obes Relat Dis ; 19(8): 851-857, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36854643

RESUMEN

BACKGROUND: Bariatric surgical patients are vulnerable to cardiopulmonary depressant effects of opioids. The enhanced recovery after surgery (ERAS) protocol to improve postoperative morbidity recommends regional anesthesia for postoperative pain management. However, there is limited evidence that peripheral nerve blocks (PNB) have added benefit. OBJECTIVE: Study the effect of PNB on postoperative pain and opioid use following bariatric surgery. SETTING: Academic medical center, United States. METHODS: We conducted a cohort study of patients who underwent sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) surgery. A total of 44 patients received the control ERAS protocol with preoperative oral extended-release morphine sulfate (MS), while 45 patients underwent a PNB with either intrathecal morphine (IM) or oral MS per local ERAS protocol. The PNB group either underwent preoperative bilateral T7 paravertebral (PVT) PNBs (27 patients) with IM or postoperative transversus abdominis plane (TAP) PNBs (18 patients) with oral MS. The primary outcome compared total opioid consumption between the ERAS control group and the PNB group up to 48 hours postoperatively. Secondary outcomes included comparison by block type and postoperative pain scores. RESULTS: PVT or TAP PNB patients had a reduction in mean postoperative oral morphine equivalent (OME) requirements compared with the ERAS protocol cohort at 24 hours (93.9 versus 42.8 mg), P < .0001; at 48 hours (72.6 versus 40.5 mg); and in pain scores at 24 hours (5.64/10 versus 4.46/10), P = .02. OME and pain scores were higher in the SG cohort. CONCLUSION: Addition of truncal PNB to standard ERAS protocol for bariatric surgical patients reduces postoperative total opioid consumption.


Asunto(s)
Analgésicos Opioides , Cirugía Bariátrica , Humanos , Analgésicos Opioides/uso terapéutico , Estudios de Cohortes , Morfina , Dolor
13.
Nat Prod Res ; : 1-11, 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38073405

RESUMEN

Rubus moluccanus L., commonly known as Molucca bramble or broad-leaf bramble is a member of family Rosaceae which occurs mainly in tropical Asia and Australia. It has applications in indigenous medicines and is used in the treatment of number of ailments like headache, diarrhoea, dysentery, abdominal pain, nocturnal micturition of children and enhancement of female fertility. This plant is a rich and valuable source of bioactive flavonoids, terpenes and other chemical compounds. The presence of these active chemical compounds exerts antibacterial, antifungal, antihelminthic and antioxidant activities. Regardless of its use in various diseases and disorders, the information about this plant is scanty. So the present review assessed and summarised the knowledge on taxonomy, morphology, geographical distribution, nutritional value, ethnobotany, phytochemistry and biological activities of R. moluccanus.

14.
RSC Adv ; 13(51): 36280-36292, 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38090067

RESUMEN

The level of free bilirubin is a considerable index for the characterization of jaundice-related diseases. Herein, a biosensor was fabricated via the immobilization of bilirubin oxidase (BOx) on graphene oxide (GO) and polyaniline (PANI) that were electrochemically co-precipitated on indium tin oxide (ITO) conductive glass. The structural enzyme electrode was characterized by FTIR, XRD, and Raman spectroscopy, while the spectral and thermal properties were investigated by UV-vis and thermogravimetric analysis (TGA). Owing to the activity of the fabricated BOx/GO@PANI/ITO biosensor, it could detect free bilirubin with good selectivity and sensitivity in a low response time. The electrochemical response was studied using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). At polarization potential 0.2 V vs. Ag/AgCl, the fabricated sensor illustrated a response in only 2 s at 30 °C and pH 7.5. The LOD and LOQ for the BOx/GO@PANI/ITO biosensor were calculated and found to be 0.15 nM and 2.8 nM, respectively. The electrochemical signal showed a linear response in the concentration range 0.01-250 µM. At 5 °C, the biosensor demonstrated a half-time of 120 days, through which it could be utilized 100 times at this temperature conditions. By using a common colorimetric method, the data on bilirubin levels in serum showed a determination coefficient (R2) of 0.97.

15.
Sci Adv ; 9(31): eadi1359, 2023 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-37531432

RESUMEN

Respiratory complex I, a key enzyme in mammalian metabolism, captures the energy released by reduction of ubiquinone by NADH to drive protons across the inner mitochondrial membrane, generating the proton-motive force for ATP synthesis. Despite remarkable advances in structural knowledge of this complicated membrane-bound enzyme, its mechanism of catalysis remains controversial. In particular, how ubiquinone reduction is coupled to proton pumping and the pathways and mechanisms of proton translocation are contested. We present a 2.4-Å resolution cryo-EM structure of complex I from mouse heart mitochondria in the closed, active (ready-to-go) resting state, with 2945 water molecules modeled. By analyzing the networks of charged and polar residues and water molecules present, we evaluate candidate pathways for proton transfer through the enzyme, for the chemical protons for ubiquinone reduction, and for the protons transported across the membrane. Last, we compare our data to the predictions of extant mechanistic models, and identify key questions to answer in future work to test them.


Asunto(s)
Complejo I de Transporte de Electrón , Protones , Ratones , Animales , Oxidación-Reducción , Complejo I de Transporte de Electrón/metabolismo , Ubiquinona/química , Ubiquinona/metabolismo , Microscopía por Crioelectrón , Mamíferos/metabolismo , Agua/metabolismo
16.
Elife ; 122023 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-36622099

RESUMEN

Respiratory complex I powers ATP synthesis by oxidative phosphorylation, exploiting the energy from NADH oxidation by ubiquinone to drive protons across an energy-transducing membrane. Drosophila melanogaster is a candidate model organism for complex I due to its high evolutionary conservation with the mammalian enzyme, well-developed genetic toolkit, and complex physiology for studies in specific cell types and tissues. Here, we isolate complex I from Drosophila and determine its structure, revealing a 43-subunit assembly with high structural homology to its 45-subunit mammalian counterpart, including a hitherto unknown homologue to subunit NDUFA3. The major conformational state of the Drosophila enzyme is the mammalian-type 'ready-to-go' active resting state, with a fully ordered and enclosed ubiquinone-binding site, but a subtly altered global conformation related to changes in subunit ND6. The mammalian-type 'deactive' pronounced resting state is not observed: in two minor states, the ubiquinone-binding site is unchanged, but a deactive-type π-bulge is present in ND6-TMH3. Our detailed structural knowledge of Drosophila complex I provides a foundation for new approaches to disentangle mechanisms of complex I catalysis and regulation in bioenergetics and physiology.


Asunto(s)
Drosophila melanogaster , Complejo I de Transporte de Electrón , Animales , Microscopía por Crioelectrón , Drosophila melanogaster/metabolismo , Complejo I de Transporte de Electrón/metabolismo , Complejo I de Transporte de Electrón/ultraestructura , Mitocondrias/metabolismo , Ubiquinona/metabolismo
17.
IET Image Process ; 2022 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-36246853

RESUMEN

Coronavirus Disease 2019 (Covid-19) overtook the worldwide in early 2020, placing the world's health in threat. Automated lung infection detection using Chest X-ray images has a ton of potential for enhancing the traditional covid-19 treatment strategy. However, there are several challenges to detect infected regions from Chest X-ray images, including significant variance in infected features similar spatial characteristics, multi-scale variations in texture shapes and sizes of infected regions. Moreover, high parameters with transfer learning are also a constraints to deploy deep convolutional neural network(CNN) models in real time environment. A novel covid-19 lightweight CNN(LW-CovidNet) method is proposed to automatically detect covid-19 infected regions from Chest X-ray images to address these challenges. In our proposed hybrid method of integrating Standard and Depth-wise Separable convolutions are used to aggregate the high level features and also compensate the information loss by increasing the Receptive Field of the model. The detection boundaries of disease regions representations are then enhanced via an Edge-Attention method by applying heatmaps for accurate detection of disease regions. Extensive experiments indicate that the proposed LW-CovidNet surpasses most cutting-edge detection methods and also contributes to the advancement of state-of-the-art performance. It is envisaged that with reliable accuracy, this method can be introduced for clinical practices in the future.

18.
J Complement Integr Med ; 19(4): 1025-1032, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34265876

RESUMEN

OBJECTIVES: Low back pain is the most widespread musculoskeletal ailment and a common cause of disability worldwide. Conventional medicine typically treats low back pain with a combination of physical therapy; activity modification and rest; pain-relieving and anti-inflammatory medications which are associated with huge socioeconomic implications and adverse drug reactions. In contrast Hijama, Dalk and Bukhur are ancient medical techniques recommended in the management of musculoskeletal disorders with little or no adverse effects. To evaluate the safety and effectiveness of Hijama bi'l Shart (wet cupping), followed by Dalk (Massage) with Roghan Dafli and Bukhur (medicated steam) with Tukhm Soya (Anethum graveolens Linn) in patients of Waja al-Zahr (Non-specific Low back pain). METHODS: Patients of either gender in the age group of 18-50 years with low back pain persisting for four weeks or more as chief complaint were recruited in the trial. The study was GCP compliant. The duration of the protocol therapy carried out was 14 days. RESULTS: Ninty two patients of NSLBP were screened, of which 34 who fulfilled the inclusion criteria and were willing to participate in the study were recruited. Three participants were lost to follow-ups due to personal reasons and 31 patients completed the trial during the study period. Overall therapeutic response observed in this study was 97% while 3% of the patients did not respond to intervention. CONCLUSIONS: The study findings imply that there is a credible evidence to ensure that the regimens intervened are safe and effective in ameliorating the symptoms of Waja al-Zahr.


Asunto(s)
Dolor de la Región Lumbar , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Dolor de la Región Lumbar/terapia , Vapor , Estudios Prospectivos
19.
J Ayub Med Coll Abbottabad ; 23(4): 106-7, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-23472428

RESUMEN

BACKGROUND: External ventricular drain involves catheter placement in ventricles of brain. It is used for various purposes. Basic theme is to drain cerebrospinal fluid so as to control intracranial pressure. This study was carried out to see the effect of tunnel length on rate of infection. METHODS: This was a cross-sectional study carried out in Department of Neurosurgery, Pakistan Institute of Medical Sciences, Islamabad during 14 months from 1st December 2008 to 31 January 2010. External ventricular drain was placed in admitted patients after meticulous aseptic technique in operation theatre at right Kocher's point. It was carried out through a scalp tunnel and was connected to drainage bag through a drip set. Both long (> 5 Cm) and short (< 5 Cm) tunnels were randomly made. Infection rate was estimated in patients who had change of cerebrospinal fluid colour or developed fever (as per protocol to have minimum handling of drain). All patients received prophylactic Ceftriaxone. RESULTS: Among 76 patients long tunnel was made in 44 (57.9%) and short in 32 (42.1%). Three patients (3.9%) with long tunnel while 6 (7.9%) patients with short tunnel had infection. The overall infection was in 9 (11.8%) patients. CONCLUSION: External ventricular drain tunnel length strongly influences the rate of infection.


Asunto(s)
Drenaje/instrumentación , Hidrocefalia/cirugía , Infecciones Relacionadas con Prótesis/epidemiología , Ventriculostomía/instrumentación , Enfermedad Aguda , Adulto , Femenino , Humanos , Masculino , Pakistán/epidemiología , Resultado del Tratamiento
20.
J Ayub Med Coll Abbottabad ; 23(2): 118-20, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-24800360

RESUMEN

BACKGROUND: External ventricular (EVD) is a life saving procedure and involves insertion of a catheter in ventricular space to drain cerebrospinal fluid (CSF). Our objective of this study was to determine the culture and sensitivity (C/S) pattern in patients with EVD infection. METHODS: This cross sectional study was conducted in Department of Neurosurgery, Pakistan Institute of Medical Sciences (PIMS), Islamabad from December 1, 2008 to January 31, 2010. All admitted patients who had acute hydrocephalus, underwent EVD insertion after excluding meningitis and ventriculitis by physical examination and per operative CSF sampling. The EVD was done at right Kocher's point. Prophylactic third generation antibiotic (Ceftriaxone) was started and continued till EVD was in place. C/S was sent to PIMS laboratory on first documented fever and or change of CSF color or when plan was to replace EVD with Ventriculo-peritoneal shunt (VP). Once infection was there CSF was sent for C/S initially and routine examination (R/E) daily. Antibiotics were changed according to C/S report and continued till they were needed. Infection rate was also estimated. RESULTS: Among 76 patients 41 (53.9%) were male and 35 (46.1%) were females. Most were adults and were between 31 to 40 years of age. Mean duration of EVD was 11.41 days. Overall infection rate was 11.8%. Among causative organisms Staphylococcus Aureus (44.4%) was most common followed by Acenitobacter and Enterobacter and commonly used prophylactic antibiotic (Ceftriaxone) had considerable resistance. CONCLUSION: EVD is a simple and life saving procedure. Most common organisms causing infection are Staphylococcus Aureus followed by Acenitobacter. Conventional used antibiotic Ceftriaxone has considerable resistance.


Asunto(s)
Antibacterianos/uso terapéutico , Derivaciones del Líquido Cefalorraquídeo/efectos adversos , Hidrocefalia/cirugía , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/microbiología , Adulto , Profilaxis Antibiótica , Estudios Transversales , Femenino , Humanos , Masculino
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