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1.
Clin Infect Dis ; 78(5): 1204-1213, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38227643

RESUMEN

BACKGROUND: Infection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2. METHODS: We performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data. The outcome measure was any instance of healthcare transmission, defined as cases with closely related viral genomes and epidemiological connection within the healthcare setting during the infection window. Between November 2020 through January 2022, 12 933 viral genomes were obtained from 35 666 patients and HCWs. RESULTS: Among 5112 SARS-CoV-2 viral samples sequenced from the second and third waves of SARS-CoV-2 (pre-Omicron), 291 pairs were derived from persons with a plausible healthcare overlap. Of these, 34 pairs (12%) were phylogenetically linked: 19 attributable to household and 14 to healthcare transmission. During the Omicron wave, 2106 contact pairs among 7821 sequences resulted in 120 (6%) related pairs among 32 clusters, of which 10 were consistent with healthcare transmission. Transmission was more likely to occur in shared spaces in the older hospital compared with the newer hospital (2.54 vs 0.63 transmission events per 1000 admissions, P < .001). CONCLUSIONS: IP strategies were effective at identifying and preventing healthcare SARS-CoV-2 transmission.


Asunto(s)
COVID-19 , Genoma Viral , Personal de Salud , SARS-CoV-2 , Humanos , COVID-19/transmisión , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/genética , Estudios Retrospectivos , Estudios Transversales , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Análisis de Redes Sociales , Trazado de Contacto , Genómica , Adulto Joven , Adolescente , Niño , Anciano de 80 o más Años , Infección Hospitalaria/transmisión , Infección Hospitalaria/virología , Infección Hospitalaria/epidemiología , Preescolar
2.
Semin Cancer Biol ; 86(Pt 2): 436-449, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35700938

RESUMEN

Colorectal cancer (CRC) is considered the second cause of cancer death worldwide. The early diagnosis plays a key role in patient prognosis and subsequently overall survival. Similar to several types of cancer, colorectal cancer is also characterised by drug resistance and heterogeneity that contribute to its complexity -especially at advanced stages. However, despite the extensive research related to the identification of biomarkers associated to early diagnosis, accurate prognosis and the management of CRC patients, little progress has been made thus far. Therefore, the mortality rates, especially at advanced stages, remain high. A large family of chemoattractant cytokines called chemokines are known for their significant role in inflammation and immunity. Chemokines released by the different tumorous cells play a key role in increasing the complexity of the tumour's microenvironment. The current review investigates the role of chemokines and chemokine receptors in colorectal cancer and their potential as clinical molecular signatures that could be effectively used as a personalised therapeutic approach. We discussed how chemokine and chemokine receptors regulate the microenvironment and lead to heterogeneity in CRC. An important aspect of chemokines is their role in drug resistance which has been extensively discussed. This review also provides an overview of the current advances in the search for chemokines and chemokine receptors in CRC.


Asunto(s)
Neoplasias Colorrectales , Receptores de Quimiocina , Humanos , Detección Precoz del Cáncer , Quimiocinas , Pronóstico , Neoplasias Colorrectales/genética , Microambiente Tumoral/genética
3.
J Neurooncol ; 163(2): 439-446, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37227651

RESUMEN

PURPOSE: Optic neuropathy is a rare, delayed complication after radiation with no universally accepted treatment modality. We report the outcomes of 6 patients with radiation-induced optic neuropathy (RION) who were treated with systemic bevacizumab. METHODS: This is a retrospective series of 6 cases of RION, treated with intravenous (IV) bevacizumab. "Improved" or "worse" visual outcomes were defined as a change in best corrected visual acuity of ≥ 3 Snellen lines. Otherwise, the visual outcome was noted as "stable". RESULTS: In our series, RION was diagnosed 8 to 36 months after radiotherapy. IV bevacizumab was initiated as treatment within 6 weeks of the onset of visual symptoms in 3 cases and after 3 months in the other cases. Although no improvement in visual function was observed, stabilization of vision was noted in 4 of the 6 cases. In the other 2 cases, the level of vision declined from counting fingers to no light perception. In 2 cases, bevacizumab treatment was discontinued prior to completion of the planned course due to renal stone formation or worsening of renal disease. One patient developed ischemic stroke 4 months after bevacizumab completion. CONCLUSION: Systemic bevacizumab may stabilize vision in some patients with RION, though the limitations of our study do not allow us to draw this conclusion definitively. Therefore, the risks and potential benefits of using IV bevacizumab should be considered in each individual case.


Asunto(s)
Enfermedades del Nervio Óptico , Humanos , Bevacizumab/uso terapéutico , Estudios Retrospectivos , Enfermedades del Nervio Óptico/tratamiento farmacológico , Enfermedades del Nervio Óptico/etiología , Nervio Óptico , Agudeza Visual
4.
Lancet ; 398 Suppl 1: S36, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34227969

RESUMEN

BACKGROUND: Ongoing protests in Gaza have led to numerous injuries, including long-bone fractures. We investigated assessment of pain severity and strategies for pain management in the emergency department. As no local guidelines exist, delivered care was compared with the guidance of the UK National Institute for Health and Care Excellence (NICE). METHODS: A clinical audit was conducted at the emergency department in Dar Al Shifa Medical Complex, Gaza, among patients who attended the emergency department with acute long-bone fractures between April 15 and July 15, 2018. Data were collected on pain assessment methods and strategies for pain management and analgesia administration. Ethics approval was obtained from the Palestinian Ministry of Health. The purpose of the audit was explained to patients and their written consent was obtained before inclusion. FINDINGS: Of 79 patients invited to participate, 50 gave consent. 25 patients (50%) were aged 16-24 years, 20 (40%) 25-64 years, and five (10%) 65 years and older. Structured pain assessments were performed in only three patients (6%). No analgesia was administered to patients in the emergency department, except for two patients (4%) received infiltration of lidocaine as analgesia for haematoma. INTERPRETATION: No local guidelines for acute pain management in emergency departments exist in the Gaza Strip. Clinical practice showed no adherence to international standards, such as the NICE guidelines for pain management. Factors contributing to such poor management might be large numbers of patients presenting at the time during conflict and protests and that only one room was available in the Shifa' Medical Complex emergency department for examining, assessment, prescribing, and cast application. A limitation of the study is the small sample size is relatively small, but strengths were the 3-month period and prospective enrolment in the emergency department. FUNDING: None.

5.
PLoS Comput Biol ; 17(9): e1009384, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34516563

RESUMEN

Apart from the canonical fingers, palm and thumb domains, the RNA dependent RNA polymerases (RdRp) from the viral order Nidovirales possess two additional domains. Of these, the function of the Nidovirus RdRp associated nucleotidyl transferase domain (NiRAN) remains unanswered. The elucidation of the 3D structure of RdRp from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), provided the first ever insights into the domain organisation and possible functional characteristics of the NiRAN domain. Using in silico tools, we predict that the NiRAN domain assumes a kinase or phosphotransferase like fold and binds nucleoside triphosphates at its proposed active site. Additionally, using molecular docking we have predicted the binding of three widely used kinase inhibitors and five well characterized anti-microbial compounds at the NiRAN domain active site along with their drug-likeliness. For the first time ever, using basic biochemical tools, this study shows the presence of a kinase like activity exhibited by the SARS-CoV-2 RdRp. Interestingly, a well-known kinase inhibitor- Sorafenib showed a significant inhibition and dampened viral load in SARS-CoV-2 infected cells. In line with the current global COVID-19 pandemic urgency and the emergence of newer strains with significantly higher infectivity, this study provides a new anti-SARS-CoV-2 drug target and potential lead compounds for drug repurposing against SARS-CoV-2.


Asunto(s)
Antivirales/farmacología , ARN Polimerasa Dependiente de ARN de Coronavirus/antagonistas & inhibidores , Dominios Proteicos , SARS-CoV-2/efectos de los fármacos , Dominio Catalítico , Simulación por Computador , ARN Polimerasa Dependiente de ARN de Coronavirus/química , ARN Polimerasa Dependiente de ARN de Coronavirus/metabolismo , Humanos
6.
Eur Child Adolesc Psychiatry ; 29(1): 51-61, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31190178

RESUMEN

Mental health is a key component of health, yet appropriate care is limited. Evidence concerning child and adolescent mental health has predominantly come from western countries, while the Middle East region, with a large youth population, has reported very little on it. This original, cross-sectional study of child and adolescent psychiatry in the Middle East provides an assessment of current postgraduate programs, services and what is needed to build workforce capacity. Academic psychiatrists from 16 Middle East countries were invited to form a Consortium to map current postgraduate training as one of the determinants of available child and adolescent psychiatry services, identify gaps in the distribution of child and adolescent psychiatrists, and propose potential steps to improve access to child and adolescent mental health care. The study collected data from 15 of the 16 countries invited (no data provided from Yemen). The study revealed underdeveloped child and adolescent psychiatry academic systems throughout the region. Despite recognition of the specialty in a majority of the countries (11/15), only six countries had established a designated child and adolescent psychiatry training program. The overall shortage of child and adolescent mental health specialists varied, yet all Consortium members reported a need for additional child and adolescent psychiatry specialists and allied professionals. Lack of child and adolescent psychiatry specialized programs in place throughout the region has evidently contributed to the shortage of qualified child and adolescent mental health workforce in the Middle East.


Asunto(s)
Psiquiatría del Adolescente/educación , Psiquiatría Infantil/educación , Educación Médica/métodos , Adolescente , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Medio Oriente
7.
Am J Med Genet A ; 173(1): 190-194, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27862896

RESUMEN

Despite considerable progress in identifying causal genes for lipodystrophy syndromes, the molecular basis of some peculiar adipose tissue disorders remains obscure. In an Israeli-Arab pedigree with a novel autosomal recessive, multiple symmetric lipomatosis (MSL), partial lipodystrophy and myopathy, we conducted exome sequencing of two affected siblings to identify the disease-causing mutation. The 41-year-old female proband and her 36-year-old brother reported marked accumulation of subcutaneous fat in the face, neck, axillae, and trunk but loss of subcutaneous fat from the lower extremities and progressive distal symmetric myopathy during adulthood. They had increased serum creatine kinase levels, hypertriglyceridemia and low levels of high-density lipoprotein cholesterol. Exome sequencing identified a novel homozygous NC_000019.9:g.42906092C>A variant on chromosome 19, leading to a NM_005357.3:c.3103G>T nucleotide change in coding DNA and corresponding p.(Glu1035*) protein change in hormone sensitive lipase (LIPE) gene as the disease-causing variant. Sanger sequencing further confirmed the segregation of the mutation in the family. Hormone sensitive lipase is the predominant regulator of lipolysis from adipocytes, releasing free fatty acids from stored triglycerides. The homozygous null LIPE mutation could result in marked inhibition of lipolysis from some adipose tissue depots and thus may induce an extremely rare phenotype of MSL and partial lipodystrophy in adulthood associated with complications of insulin resistance, such as diabetes, hypertriglyceridemia and hepatic steatosis. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Homocigoto , Lipodistrofia/genética , Lipomatosis Simétrica Múltiple/genética , Enfermedades Musculares/genética , Mutación , Hermanos , Esterol Esterasa/genética , Adulto , Anciano , Biomarcadores , Análisis Mutacional de ADN , Exoma , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Lipodistrofia/diagnóstico , Lipodistrofia/metabolismo , Lipomatosis Simétrica Múltiple/diagnóstico , Lipomatosis Simétrica Múltiple/metabolismo , Masculino , Persona de Mediana Edad , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/metabolismo , Linaje , Fenotipo , Adulto Joven
8.
Biosci Biotechnol Biochem ; 81(8): 1642-1649, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28585494

RESUMEN

The natural coagulant Moringa oleifera lectin (MoL) as cationic protein is a promising candidate in coagulation process of water treatment plant. Introducing the gene encoding MoL into a host, Pichia pastoris, to secrete soluble recombinant protein is assessed in this study. Initial screening using PCR confirmed the insertion of MoL gene, and SDS-PAGE analysis detected the MoL protein at 8 kDa. Cultured optimization showed the highest MoL protein at 520 mg/L was observed at 28 °C for 144 h of culturing by induction in 1% methanol. Approximately, 0.40 mg/mL of recombinant MoL protein showed 95 ± 2% turbidity removal of 1% kaolin suspension. In 0.1% kaolin suspension, the concentration of MoL at 10 µg/mL exhibits the highest turbidity reduction at 68 ± 1%. Thus, recombinant MoL protein from P. pastoris is an effective coagulant for water treatment.


Asunto(s)
Caolín/aislamiento & purificación , Moringa oleifera/química , Lectinas de Plantas/genética , Contaminantes Químicos del Agua/aislamiento & purificación , Purificación del Agua/métodos , Clonación Molecular , Floculación/efectos de los fármacos , Expresión Génica , Humanos , Moringa oleifera/metabolismo , Nefelometría y Turbidimetría , Pichia/genética , Pichia/metabolismo , Lectinas de Plantas/biosíntesis , Lectinas de Plantas/química , Lectinas de Plantas/farmacología , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacología , Agua/química
9.
J Pak Med Assoc ; 66(8): 994-8, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27524535

RESUMEN

OBJECTIVE: To assess the frequency and its correlation of patient fall with preventing or precipitating factors among inpatients. METHODS: The observational study was conducted in Makkah Region, Saudi Arabia from October 15 2012 to November 4, 2013. Data was collected using a questionnaire from 16 hospitals in four districts of Makkah province. The material was sampled through systematic randomisation from inpatient files and data was collected for those who had fallen inside the hospital. The questionnaire, validated through a pilot study run under the Directorate of Quality and Patient Safety in Makkah, was used to see whether the hospitals had adopted and applied international standards for assessment of adult and paediatric patients for falls as well as effectiveness of these applications. RESULTS: Of 4,799 beds, occupancy rates ranged from 1680(35%) to 4,799(100%). Out of 291 falls in all, 144(49.48%) were in Jeddah. Besides, 116(40%) of the falls occurred in the last quarter of the Islamic calendar. Statistically significant difference was found in fall episodes in different months (p=0.007). Statistical analysis indicated that the factors that significantly raised the number of patient falls were increase in hospital beds and their occupancy rate (Spearman's correlation: 0.621 and 0.579 respectively). CONCLUSIONS: The frequency of falls varied from hospital to hospital and factors like higher number of bed capacity and occupancy rate increased the falls.


Asunto(s)
Accidentes por Caídas/estadística & datos numéricos , Ocupación de Camas/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Tamaño de las Instituciones de Salud/estadística & datos numéricos , Hospitalización , Unidades de Cuidados Intensivos/estadística & datos numéricos , Administración de Personal/estadística & datos numéricos , Prevención de Accidentes , Accidentes por Caídas/prevención & control , Hospitales/estadística & datos numéricos , Humanos , Seguridad del Paciente , Proyectos Piloto , Medición de Riesgo , Arabia Saudita , Encuestas y Cuestionarios
10.
Toxicol Mech Methods ; 24(2): 116-23, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24175857

RESUMEN

CONTEXT: Obesity has become a worldwide health problem. Most of the synthetic anti-obesity drugs have failed to manage the obesity due to either ineffectiveness or adverse effect. The research of prominent chemical constituents from herbal for the management of obesity has greatly increased. OBJECTIVE: The main objective of the present study was intended to examine the effects of thymol in high-fat diet (HFD)-induced obesity in murine model. METHODS: Male Wistar rats were fed HFD for 6 weeks to induce obesity. Thymol (14 mg/kg) administered orally twice a day to HFD-fed rats for 4 weeks. Alteration in body weight gain, visceral fat-pads weight and serum biochemical markers were assessed. RESULTS: At the end of study, rats fed with HFD exhibited significantly (p < 0.001) enhanced body weight gain, visceral pad weight, lipids, alanine aminotransferase (ALT), aspartate aminotransaminase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), glucose, insulin and leptin levels compared with rats fed with normal diets. Thymol treatment showed significantly (p < 0.001) decreased body weight gain, visceral fat-pad weights, lipids, ALT, AST, LDH, BUN, glucose, insulin, and leptin levels in HFD-induced obese rats. Furthermore, thymol treatment showed significantly decreased serum lipid peroxidation and increased antioxidant levels in HFD-induced obese rats. DISCUSSION AND CONCLUSIONS: Thymol prevents HFD-induced obesity in murine model through several mechanisms including attenuation of visceral fat accumulation, lipid lowering action, improvement of insulin and leptin sensitivity and enhanced antioxidant potential.


Asunto(s)
Dieta Alta en Grasa , Modelos Animales de Enfermedad , Obesidad/inducido químicamente , Timol/uso terapéutico , Animales , Antioxidantes/metabolismo , Biomarcadores/sangre , Peso Corporal/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Pruebas de Función Renal , Pruebas de Función Hepática , Masculino , Ratones , Obesidad/sangre , Obesidad/etiología , Tamaño de los Órganos/efectos de los fármacos , Ratas Wistar , Timol/farmacología
11.
Front Immunol ; 14: 1254911, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37869015

RESUMEN

Siglecs are well known immunotherapeutic targets in cancer. Current checkpoint inhibitors have exhibited limited efficacy, prompting a need for novel therapeutics for targets such as Siglec-15. Presently, small molecule inhibitors targeting Siglec-15 are not explored alongside characterised regulatory mechanisms involving microRNAs in CRC progression. Therefore, a small molecule inhibitor to target Siglec-15 was elucidated in vitro and microRNA mediated inhibitor effects were investigated. Our research findings demonstrated that the SHG-8 molecule exerted significant cytotoxicity on cell viability, migration, and colony formation, with an IC50 value of approximately 20µM. SHG-8 exposure induced late apoptosis in vitro in SW480 CRC cells. Notably, miR-6715b-3p was the most upregulated miRNA in high-throughput sequencing, which was also validated via RT-qPCR. MiR-6715b-3p may regulate PTTG1IP, a potential oncogene which was validated via RT-qPCR and in silico analysis. Additionally, molecular docking studies revealed SHG-8 interactions with the Siglec-15 binding pocket with the binding affinity of -5.4 kcal/mol, highlighting its role as a small molecule inhibitor. Importantly, Siglec-15 and PD-L1 are expressed on mutually exclusive cancer cell populations, suggesting the potential for combination therapies with PD-L1 antagonists.


Asunto(s)
Neoplasias Colorrectales , MicroARNs , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico , Humanos , Apoptosis/genética , Antígeno B7-H1/genética , Proliferación Celular/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Simulación del Acoplamiento Molecular , Oncogenes , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico/antagonistas & inhibidores
12.
Int J Biol Macromol ; 229: 515-528, 2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36584781

RESUMEN

Given the paucity of antiviral treatments for monkeypox disease, caused by the Monkeypox virus (MPXV), there is a pressing need for the development/identification of new drugs to treat the infection. MPXV possesses a linear dsDNA genome that is replicated by a DNA replication complex of which DNA polymerase (DPol) forms an important component. Owing to the importance of DPol in the viral life cycle, identifying/designing small molecules abolishing its function could yield new antivirals. In this study, we first used the AlphaFold artificial intelligence program to model the 3D structure of the MPXV DPol; like the fold of DPol from other organisms, the MPXV DPol structure has the characteristic exonuclease, thumb, palm, and fingers sub-domains arrangement. Subsequently, we have identified several inhibitors through virtual screening of ZINC and antiviral libraries. Molecules with phenyl scaffold along with alanine-based and tetrazole-based molecules showed the best docking score of -8 to -10 kcal/mol. These molecules bind in the palm and fingers sub-domains interface region, which partially overlaps with the DNA binding path. The delineation of DPol/inhibitor interactions showed that majorly active site residues ASP549, ASP753, TYR550, ASN551, SER552, and ASN665 interact with the inhibitors. These compounds exhibit good Absorption, Distribution, Metabolism and Excretion properties.


Asunto(s)
Monkeypox virus , Mpox , Humanos , Monkeypox virus/genética , Inteligencia Artificial , Mpox/diagnóstico , ADN Polimerasa Dirigida por ADN , Antivirales/farmacología
13.
Ann Med Surg (Lond) ; 85(11): 5816-5819, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37915630

RESUMEN

Introduction: Idiopathic occlusion of the Foramen of Monro is extremely rare in adults. The occlusion is classified into four types, with the first being the most infrequent. This condition induces noncommunicating hydrocephalus with the ensuing increased intracranial pressure symptoms. Headache is usually the chief complaint. Presentation of the case: The authors present a case of a 28-year-old female who presented with a chronic headache that was unresponsive to analgesics. No other neurological deficits were present. Fundoscopic examination revealed the presence of bilateral papillary edema. Computed tomography scan results showed bilateral enlargement of the lateral ventricles of the brain. A subsequent MRI scan ruled out secondary causes of occlusion, such as colloid cysts, meningiomas, or choroid plexus tumors, which entailed an idiopathic etiology.Treatment options include ventriculoperitoneal shunt insertion and septostomy with foraminoplasty. The former option is currently the treatment of choice, yet it is notorious for its ramifications, including foreign body reaction, breakage, and mechanical problems. The latter option is free of these risks; however, it requires meticulousness and precision to avoid damaging the fornix, which leads to impaired memory function. Conclusion: Septostomy with unilateral foraminoplasty could yield better outcomes if it is performed fastidiously.

14.
IUCrJ ; 10(Pt 6): 738-753, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37860976

RESUMEN

Enolase, a ubiquitous enzyme, catalyzes the reversible conversion of 2-phosphoglycerate (2PG) to phosphoenolpyruvate (PEP) in the glycolytic pathway of organisms of all three domains of life. The underlying mechanism of the 2PG to PEP conversion has been studied in great detail in previous work, however that of the reverse reaction remains to be explored. Here we present structural snapshots of Mycobacterium tuberculosis (Mtb) enolase in apo, PEP-bound and two 2PG-bound forms as it catalyzes the conversion of PEP to 2PG. The two 2PG-bound complex structures differed in the conformation of the bound product (2PG) viz the widely reported canonical conformation and a novel binding pose, which we refer to here as the alternate conformation. Notably, we observed two major differences compared with the forward reaction: the presence of MgB is non-obligatory for the reaction and 2PG assumes an alternate conformation that is likely to facilitate its dissociation from the active site. Molecular dynamics studies and binding free energy calculations further substantiate that the alternate conformation of 2PG causes distortions in both metal ion coordination and hydrogen-bonding interactions, resulting in an increased flexibility of the active-site loops and aiding product release. Taken together, this study presents a probable mechanism involved in PEP to 2PG catalysis that is likely to be mediated by the conformational change of 2PG at the active site.


Asunto(s)
Mycobacterium tuberculosis , Fosfopiruvato Hidratasa , Fosfopiruvato Hidratasa/química , Conformación Proteica , Modelos Moleculares , Catálisis
15.
Prog Orthod ; 24(1): 22, 2023 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-37303011

RESUMEN

BACKGROUND: The introduction of bone-anchored maxillary protraction eliminated the side effects of facemask in the early treatment of patients with maxillary retrusion. This study aimed to evaluate the effects of miniscrew-anchored maxillary protraction (MAMP) and compare them with the growth changes in an untreated control group in growing patients with Class III malocclusion. METHODS: Forty growing patients with Class III malocclusion and retrognathic maxilla were randomly allocated into two groups: treated and control groups. In the treated group, patients were treated with full-time intermaxillary Class III elastics (C3E) anchored by a hybrid hyrax (HH) in the maxilla and a bone-supported bar in the mandible. Protraction was stopped after obtaining a positive overjet. Cephalometric radiographs were acquired before and after the treatment. Data were statistically analyzed on an intention-to-treat basis. Intergroup comparisons were also made using analysis of covariance with the readings at T0 as a covariate. RESULTS: Forty patients agreed to participate, and 30 of them completed the study (treated group, n = 17; control group, n = 13). The average treatment duration was 11.9 months. MAMP resulted in a significant maxillary advancement (A-VR, 4.34 mm) with significant control over the mandibular growth. No significant increase in the mandibular plane angle was found in the treated group compared with the control group. The upper and lower incisors showed significant protrusion in the treated group. CONCLUSIONS: Within the limitations of this study and high attrition rate, the MAMP protocol can effectively increase maxillary forward growth with good control over the growth of the mandible antero-posteriorly and vertically.


Asunto(s)
Maloclusión de Angle Clase III , Sobremordida , Humanos , Niño , Maxilar , Mandíbula , Cefalometría , Duración de la Terapia , Maloclusión de Angle Clase III/terapia
16.
Artículo en Inglés | MEDLINE | ID: mdl-36673870

RESUMEN

(1) Background: Cancer screening tests discover cancer at early stages, even before symptoms appear. When abnormal tissues or a malignant mass is found early, treatment and cure rates are improved. In late stages, the cancer may have grown and metastasized. This can negatively affect cancer treatment and reduce the overall survival rate. Screening tests are performed when a person is asymptomatic. Public awareness about cancer screening is crucial for the success of cancer screening programs and for consequently decreasing the morbidity and mortality rate due to cancer. (2) Aim: Assess the knowledge and perception of the community regarding cancer screening in Saudi Arabia. (3) Methodology: A descriptive cross-sectional study targeting the general population of Saudi Arabia was conducted from January to June 2022. The data were collected using a structured validated electronic questionnaire. The study questionnaire covered participants' personal data, medical history, source of data, and participants' knowledge, attitude, and practice items. The questionnaire was used as a digital survey and was distributed electronically to the target population. (4) Results: A total of 1313 participants completed the study questionnaire. The participants' ages ranged from 18 to 67 years, with a mean age of 28.3 ± 11.4 years old. Overall, 60.4% of the study participants knew about cancer screening. Regarding the benefits of cancer screening, 91.8% of the participants reported knowing that the early detection of cancer helps treatment, and 81.1% knew that the early detection of cancer improves treatment outcomes. Moreover, 441 (33.6%) of the participants had good knowledge regarding cancer and cancer screening, while 872 (66.4%) had poor levels of knowledge. Furthermore, 106 (8.1%) of the participants underwent cancer screening. (5) Conclusions: The study results revealed that participants' awareness regarding cancer and cancer screening was low, especially for approaches to reduce cancer risk. Additionally, the study participants' practice regarding cancer screening was low. The health care authority should plan for population-based efficacious cancer screening programs. In addition, cancer screening information and the benefits of early detection can be disseminated through social media to target the desired populations.


Asunto(s)
Detección Precoz del Cáncer , Neoplasias , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Conocimientos, Actitudes y Práctica en Salud , Arabia Saudita/epidemiología , Estudios Transversales , Factores de Riesgo , Neoplasias/diagnóstico
17.
Front Public Health ; 11: 1156782, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37325312

RESUMEN

Background: COVID-19 was declared as a Public Health Emergency of International Concern on 30th January 2020. Compared to the general population, healthcare workers and their families have been identified to be at a higher risk of getting infected with COVID-19. Therefore, it is crucial to understand the risk factors responsible for the transmission of SARS-CoV-2 infection among health workers in different hospital settings and to describe the range of clinical presentations of SARS-CoV-2 infection among them. Methodology: A nested case-control study was conducted among healthcare workers who were involved in the care of COVID-19 cases for assessing the risk factors associated with it. To get a holistic perspective, the study was conducted in 19 different hospitals from across 7 states (Kerala, Tamil Nadu, Andhra Pradesh, Karnataka, Maharashtra, Gujarat, and Rajasthan) of India covering the major government and private hospitals that were actively involved in COVID-19 patient care. The study participants who were not vaccinated were enrolled using the incidence density sampling technique from December 2020 to December 2021. Results: A total of 973 health workers consisting of 345 cases and 628 controls were recruited for the study. The mean age of the participants was observed to be 31.17 ± 8.5 years, with 56.3% of them being females. On multivariate analysis, the factors that were found to be significantly associated with SARS-CoV-2 were age of more than 31 years (adjusted odds ratio [aOR] 1.407 [95% CI 1.53-1.880]; p = 0.021), male gender (aOR 1.342 [95% CI 1.019-1.768]; p = 0.036), practical mode of IPC training on personal protective equipment (aOR 1. 1.935 [95% CI 1.148-3.260]; p = 0.013), direct exposure to COVID-19 patient (aOR 1.413 [95% CI 1.006-1.985]; p = 0.046), presence of diabetes mellitus (aOR 2.895 [95% CI 1.079-7.770]; p = 0.035) and those received prophylactic treatment for COVID-19 in the last 14 days (aOR 1.866 [95% CI 0.201-2.901]; p = 0.006). Conclusion: The study was able to highlight the need for having a separate hospital infection control department that implements IPC programs regularly. The study also emphasizes the need for developing policies that address the occupational hazards faced by health workers.


Asunto(s)
COVID-19 , Femenino , Humanos , Masculino , Adulto Joven , Adulto , COVID-19/epidemiología , SARS-CoV-2 , Estudios de Casos y Controles , India/epidemiología , Factores de Riesgo , Personal de Salud
18.
Artículo en Inglés | MEDLINE | ID: mdl-38357608

RESUMEN

Background: Associations between retinal venous occlusion (RVO), elevated intraocular pressure, and glaucoma have been reported. Further investigations into structural alterations in the fellow eyes of individuals with unilateral RVO have revealed that the peripapillary retinal nerve fiber layer is thinner than in healthy eyes, suggesting that there may be systemic risk factors common to both RVO and glaucoma. We aimed to evaluate changes in peripapillary retinal nerve fiber layer thickness (pRNFLT) among individuals with unilateral branch retinal vein occlusion (BRVO). Methods: This prospective observational study recruited 30 individuals (60 eyes) with newly diagnosed unilateral BRVO and macular edema, and a control group of 30 healthy individuals (30 eyes) with no abnormalities on fundus examination or concurrent systemic comorbidities. After baseline measurements, the participants were reassessed at 6, 12, and 24 months by measuring global and sectoral pRNFLT using spectral-domain optical coherence tomography. Results: The mean age and sex distributions were comparable between the patient and control groups (both P > 0.05). When compared to fellow eyes, global and sectoral pRNFLT in eyes with BRVO were significantly higher at baseline (all P < 0.05). Over time, pRNFLT decreased dramatically, and by the conclusion of the two-year follow-up, there was a significant reduction from baseline in the affected eyes (all P < 0.05). Likewise, affected eyes experienced a significant improvement in best-corrected distance visual acuity and central macular thickness over the two-year follow-up (both P ≤ 0.001). Comparing the global and all-sector pRNFLT of fellow eyes in the patient group with those of normal eyes in the control group, there were no significant differences at any visit, except in the temporal sector, which revealed a significant reduction in pRNFLT at 24 months in the fellow eyes of patients with unilateral BRVO (P = 0.02). Conclusions: Patients with unilateral BRVO experienced a significant reduction in pRNFLT in the affected eyes and, to a lesser extent, in the fellow eyes, compared with that of the control arm, suggesting that they are prone to retinal nerve fiber layer damage. The reduction in pRNFLT in the normal fellow eyes of patients with BRVO may be attributed to age or concurrent systemic comorbidities. Further studies with long follow-up periods are required to shed light on the etiology of functional and structural changes in both the retinal nerve fiber layer and ganglion cell complex in the normal and affected eyes of patients with unilateral BRVO.

19.
Inhal Toxicol ; 24(10): 667-75, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22906173

RESUMEN

CONTEXT: Tobacco smoking represents a global public health threat, claiming approximately 5 million lives a year. Waterpipe tobacco use has become popular particularly among youth in the past decade, buttressed by the perception that the waterpipe "filters" the smoke, rendering it less harmful than cigarette smoke. OBJECTIVE: In this study, we examined the acute exposure of waterpipe smoking on lung inflammation and oxidative stress in mice, and compared that to cigarette smoking. MATERIALS AND METHODS: Mice were divided into three groups; fresh air control, cigarette and waterpipe. Animals were exposed to fresh air, cigarette, or waterpipe smoke using whole body exposure system one hour daily for 7 days. RESULTS: Both cigarette and waterpipe smoke exposure resulted in elevation of total white blood cell count, as well as absolute count of neutrophils, macrophages, and lymphocytes (P < 0.01). Both exposures also elevated proinflammatory markers such as TNF-α and IL-6 in BALF (P < 0.05), and oxidative stress markers including GPx activity in lungs (P < 0.05). Moreover, waterpipe smoke increased catalase activity in the lung (P < 0.05). However, none of the treatments altered IL-10 levels. DISCUSSION AND CONCLUSION: Results of cigarette smoking confirmed previous finding. Waterpipe results indicate that, similar to cigarettes, exposure to waterpipe tobacco smoke is harmful to the lungs.


Asunto(s)
Filtración/métodos , Mediadores de Inflamación/metabolismo , Pulmón/metabolismo , Estrés Oxidativo , Mucosa Respiratoria/metabolismo , Fumar/efectos adversos , Fumar/metabolismo , Agua/química , Animales , Cámaras de Exposición Atmosférica , Biomarcadores , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Recuento de Células , Femenino , Jordania , Leucocitos/inmunología , Pulmón/enzimología , Pulmón/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Oxidorreductasas/metabolismo , Distribución Aleatoria , Mucosa Respiratoria/enzimología , Mucosa Respiratoria/inmunología , Fumar/sangre , Fumar/inmunología
20.
Oman J Ophthalmol ; 15(1): 43-48, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35388246

RESUMEN

BACKGROUND: Cataract is a major complication of uveitis in children that requires timely management to restore good vision and prevent amblyopia. In surgical management of uveitic pediatric cataracts, published literature has shown a variety of clinical factors affecting the final visual outcome. The aim of this study is to investigate and report the clinical outcomes of cataract surgery and contributing factors impacting such outcomes in children with uveitis. MATERIALS AND METHODS: A retrospective case series of all pediatric patients (<18 years) who were diagnosed with uveitis and had cataract surgery at a tertiary eye institutions, between January 2000 and October 2016. Outcomes measures include best-corrected visual acuity (BCVA) and postoperative complications. Success was defined as BCVA of ≥20/60. Factors related to successful outcome were analyzed. RESULTS: The study sample was comprised of 26 patients (39 eyes). The median postoperative follow-up was 6.4 years. At the last follow-up, only 2 eyes had active uveitis, 3 eyes were controlled without medications, and 34 eyes were controlled with systemic or topical medications. At the last follow-up, 64% of eyes had BCVA ≥20/60. Anterior uveitis and postoperative aphakia were two determinants, in statistically significant manner, found to be positively related to clinical success (P = 0.01 and 0.04, respectively). Etiology of uveitis and use of preoperative intravenous methylprednisolone were not related to the success of obtaining BCVA ≥20/60 (P = 0.5 and 0.99, respectively). CONCLUSIONS: Cataract surgery improves the visual function of children with clinically significant uveitic cataracts. In this study, we found diagnosis of anterior uveitis and postoperative aphakia to be associated with better final postoperative visual outcomes.

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