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Chemosensor N7R1 with two acidic binding sites was synthesized, and the ability of the sensor to differentiate arsenite and arsenate in the organo-aqueous medium was evaluated using colorimetric sensing methods. N7R1 distinguished arsenite with a peacock blue color and arsenate with a pale green color in a DMSO/H2O (9 : 1, v/v) solvent mixture. The specific selectivity for arsenite was achieved in DMSO/H2O (7 : 3, v/v). The sensor demonstrated stability over a pH range of 5 to 12. The computed high binding constant of 9.3176 × 1011 M-2 and a lower detection limit of 11.48 ppb for arsenite exposed the chemosensor's higher potential for arsenite detection. The binding mechanism with a 1 : 2 binding process is confirmed using UV-Vis and 1H NMR titrations, electrochemical studies, mass spectral analysis and DFT calculations. Practical applications were demonstrated by utilizing test strips and molecular logic gates. Chemosensor N7R1 successfully detected arsenite in real water samples, as well as honey and milk samples.
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BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. CONCLUSION: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.
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COVID-19 , Síndrome de Guillain-Barré , Miocarditis , Pericarditis , Trombosis de los Senos Intracraneales , Humanos , Vacuna nCoV-2019 mRNA-1273 , Vacuna BNT162 , Estudios de Cohortes , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Síndrome de Guillain-Barré/inducido químicamente , Síndrome de Guillain-Barré/epidemiología , Vacunas de ARNm , Vacunación/efectos adversos , Masculino , FemeninoRESUMEN
BACKGROUND: Antibiotic-resistant microorganisms (ARMS) are the leading cause of socio- economic loss in the world, with historical evidence linking them to increased mortality and morbidity. METHODOLOGY: In this systematic review, we highlight a new treatment approach for antibiotic-resistant infections using 'Extracellular vesicle (EVs)-based therapy,' also known as cell- and drug-free therapy. Here, we categorize and summarize studies on EVs derived from various human sources, such as tissues, bodily fluids, or their condition media, emphasizing their anti-infective properties in the treatment of various infections. In addition, we contend that human adipose tissue (HAT) is a superior source of antimicrobial EVs (aEVs) and investigate the distinct antimicrobial properties of aEVs derived from a stromal vascular fraction (SVF) of human adipose tissue. In light of this, we described the limited literature and research gaps that are essential for using SVF-aEVs as personalized precision medicine. RESULT AND DISCUSSION: The notion behind adipose-derived SVF-EVs is supported by extensive literature searches that demonstrate growing trends in EV-based medical treatments as well as the larger therapeutic potential of HAT because of its extensive history of usage in regenerative medicine. CONCLUSION: Additionally, the underlying science that explains how the inflammatory process aids in the clearance of infections and the restoration of homeostasis after the host immune system successfully defends against foreign pathogens, as well as the fact that adipose-derived SVF is a noninvasive, cost-effective source of a variety of parent immune cells that produces a good yield of EVs with the same genetic make-up as their parent cells, make this concept worthwhile. This research may thereby increase survival rates and survival quality in cases of resistant infections. Vocabulary: Drug- and cell-free therapy = Nano molecules (extracellular vesicles) used as a therapeutic source without the need for chemical drugs or cell transplantation. Anti-infection EVs (aEVs) = Nature's own anti-infection powered EVs (unmodified).
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BACKGROUND: Metastatic castration-sensitive prostate cancer (mCSPC) is commonly classified into high- and low-volume subgroups which have demonstrated differential biology, prognosis, and response to therapy. Timing of metastasis has similarly demonstrated differences in clinical outcomes; however, less is known about any underlying biologic differences between these disease states. Herein, we aim to compare transcriptomic differences between synchronous and metachronous mCSPC and identify any differential responses to therapy. PATIENTS AND METHODS: We performed an international multi-institutional retrospective review of men with mCSPC who completed RNA expression profiling evaluation of their primary tumor. Patients were stratified according to disease timing (synchronous versus metachronous). The primary endpoint was to identify differences in transcriptomic profiles between disease timing. The median transcriptomic scores between groups were compared with the Mann-Whitney U test. Secondary analyses included determining clinical and transcriptomic variables associated with overall survival (OS) from the time of metastasis. Survival analysis was carried out with the Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 252 patients were included with a median follow-up of 39.6 months. Patients with synchronous disease experienced worse 5-year OS (39% versus 79%; P < 0.01) and demonstrated lower median androgen receptor (AR) activity (11.78 versus 12.64; P < 0.01) and hallmark androgen response (HAR; 3.15 versus 3.32; P < 0.01). Multivariable Cox regression identified only high-volume disease [hazard ratio (HR) = 4.97, 95% confidence interval (CI) 2.71-9.10; P < 0.01] and HAR score (HR = 0.51, 95% CI 0.28-0.88; P = 0.02) significantly associated with OS. Finally, patients with synchronous (HR = 0.47, 95% CI 0.30-0.72; P < 0.01) but not metachronous (HR = 1.37, 95% CI 0.50-3.92; P = 0.56) disease were found to have better OS with AR and non-AR combination therapy as compared with monotherapy (P value for interaction = 0.05). CONCLUSIONS: We have demonstrated a potential biologic difference between metastatic timing of mCSPC. Specifically, for patients with low-volume disease, those with metachronous low-volume disease have a more hormone-dependent transcriptional profile and exhibit a better prognosis than synchronous low-volume disease.
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Productos Biológicos , Neoplasias de la Próstata Resistentes a la Castración , Neoplasias de la Próstata , Masculino , Humanos , Transcriptoma , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Pronóstico , Castración , Productos Biológicos/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Antagonistas de Andrógenos/uso terapéuticoRESUMEN
Novel organic receptors N3R1- N3R3 were developed for the selective colorimetric recognition of arsenite ions in the organo-aqueous media. In the 50% aq. acetonitrile media and 70% aq. DMSO media, receptors N3R2 and N3R3 showed specific sensitivity and selectivity towards arsenite anions over arsenate anions. Receptor N3R1 showed discriminating recognition of arsenite in the 40% aq. DMSO medium. All three receptors formed a 1:1 complex with arsenite and stable for a pH range of 6-12. The receptors N3R2 and N3R3 achieved a detection limit of 0.008 ppm (8 ppb) and 0.0246 ppm, respectively, for arsenite. Initial hydrogen bonding on binding with the arsenite followed by the deprotonation mechanism was well supported by the UV-Vis titration, 1H- NMR titration, electrochemical studies, and the DFT studies. Colorimetric test strips were fabricated using N3R1- N3R3 for the on-site detection of arsenite anion. The receptors are also employed for sensing arsenite ions in various environmental water samples with high accuracy.
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Protein malnutrition continues to be a major global issue. A stable animal model to address protein malnutrition and its effect on various disease conditions is necessary. In the present study, we have formulated and standardized a low protein diet (LPD) to develop a protein malnutrition model using Balb/C mice. Healthy male Balb/C mice were weaned and exposed to LPD combinations while another group exposed to normal diet (18% protein). Animal survival, change in body weight, body mass index (BMI), biochemical parameters, antioxidant status, and liver histopathology were used to confirm the development of malnourished mice model (marasmic-kwashiorkor). Mice receiving 10% protein diet showed moderate weight gain, higher BMI, and no mortality compared to the 6% protein group. The former group showed remarkable differences in BMI, biochemical and antioxidant parameters. Further, histopathological changes against the normal group at weeks 20 and 30 confirmed the development of protein malnutrition in mice on 10% protein diet. The study confirms the development of a stable, economical, reproducible, and clinically relevant protein malnutrition model using the formulated 10% protein diet. Further, the model can be used for short and long-term studies to investigate the pathophysiology of malnutrition in any disease/condition.
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Kwashiorkor , Desnutrición Proteico-Calórica , Masculino , Animales , Ratones , Ratones Endogámicos BALB C , Antioxidantes , Peso CorporalRESUMEN
Essential voice tremor (EVT) is a voice disorder resulting from dyscoordination within the laryngeal musculature. A low-frequency fluctuations of fundamental voice frequency or the strength of excitation amplitude is the main consequence of the disorder. The automatic classification of healthy control and EVT is useful tool for the clinicians. A typical automatic EVT classification involves three steps. The first step is to compute the pitch contour from the speech. The second step is to compute the features from the pitch contour, and the final step is to use a classifier to classify the features into healthy or EVT. It is shown that a high-resolution pitch contour estimated from the glottal closure instants (GCIs) is useful for EVT classification. The HPRC estimation can be very poor in the presence of noise. Hence, a probabilistic source filter model based noise robust GCI detection is used for HPRC estimation. The Empirical mode decomposition based feature extraction is used followed by a support vector machine classifier. The EVT classification performance is evaluated using recordings from 45 subjects. The proposed method is found to perform better than the baseline techniques in eight different additive noise conditions with six SNR levels.
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Temblor Esencial , Trastornos de la Voz , Voz , Humanos , Voluntarios Sanos , Trastornos de la Voz/diagnóstico , Habla , TemblorRESUMEN
Transverse myelitis (TM) has been reported in association with various vaccinations. Herein we describe a case of longitudinally extensive transverse myelitis (LETM) associated with vaccination with ChAdOx1 nCoV-19 (COVISHIELD) vaccine. A 59-year-old woman with no prior co-morbidities presented with lower extremity numbness, weakness, acute urinary retention, and constipation. Numbness gradually extended up to the lower costal margin with band like sensation. She had received the vaccine 5 days prior to the onset of the symptoms. Extensive diagnostic evaluation effectively ruled out causes other than vaccination-associated transverse myelitis. Following treatment with intravenous methylprednisolone, the patient made a significant recovery. TM may be associated with vaccination against the novel ChAdOx1 nCoV-19 vaccine and we believe this to be the first report from India of LETM associated with this vaccine.
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Mielitis Transversa , ChAdOx1 nCoV-19 , Femenino , Humanos , Hipoestesia , India , Metilprednisolona , Persona de Mediana EdadRESUMEN
Introduction: Psychiatric comorbidity has been detected in one-third of bipolar patients. The illness itself may be a precipitating factor for developing substance use and anxiety disorders. Comorbid anxiety disorders with bipolar disorder (BD) are associated with decreased chances of recovery, poorer role functioning, and quality of life, and greater likelihood of suicide attempts. Hence, identifying comorbid symptoms in remitting patients has important preventive and therapeutic implications. Aims: The aim of the study was to estimate the frequency of psychiatric comorbid symptoms in patients of bipolar affective disorder in remission and to identify its relationship with sociodemographic variables. Methodology: This is a cross-sectional study conducted in Father Muller Medical College and Hospital, Mangalore (April 2019-July 2019), which included 90 patients aged 18-50 years with BD, manic, or depressive episodes in remission for 8 weeks who were evaluated using mini international neuropsychiatric interview plus, Hamilton rating scale for depression, and young mania rating scale. Sociodemographic details were assessed by a semi-structured pro forma. The data were analyzed using frequency, Chi-square test, and t-test. Results: Most common psychiatry comorbid symptoms seen in BD were found to be drug dependence/abuse (n = 31), second most common being alcohol dependence/abuse (n = 21), followed by suicidality (n = 8), antisocial personality, social phobia, panic disorder, and agoraphobia. Significance was found for suicidality, agoraphobia, and social phobia if the last episode was depressive and for suicidality if index episode was depressive and if age of onset was >40 years. Conclusion: Psychiatric comorbidities in BD may worsen the course and prognosis of the disorder and hence, clinicians must maintain a high index of suspicion for them. Furthermore, comorbidities may need to be identified and appropriate interventions employed to prevent iatrogenic complications.
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OBJECTIVES: To assess brain white matter using diffusion tensor imaging (DTI) at 1 year of age in infants diagnosed with open neural tube defect (ONTD) and explore the association of DTI parameters with ambulatory skills at 30 months of age. METHODS: Magnetic resonance imaging (MRI) was performed at an average of 12 months of age and included an echo planar axial DTI sequence with diffusion gradients along 20 non-collinear directions. TORTOISE software was used to correct DTI raw data for motion artifacts, and DtiStudio, DiffeoMap and RoiEditor were used for further postprocessing. DTI data were analyzed in terms of fractional anisotropy (FA), trace, radial diffusivity and axial diffusivity. These parameters reflect the integrity and maturation of white-matter motor pathways. At 30 months of age, ambulation status was evaluated by a developmental pediatrician, and infants were classified as ambulatory if they were able to walk independently with or without orthoses or as non-ambulatory if they could not. Linear mixed-effects method was used to examine the association between study outcomes and study group. Possible confounders were sought, and analyses were adjusted for age at MRI scan and ventricular size by including them in the regression model as covariates. RESULTS: Twenty patients with ONTD were included in this study, including three cases that underwent postnatal repair and 17 cases that underwent prenatal repair. There were five ambulatory and 15 non-ambulatory infants evaluated at a mean age of 31.5 ± 5.7 months. MRI was performed at 50.3 (2-132.4) weeks postpartum. When DTI analysis results were compared between ambulatory and non-ambulatory infants, significant differences were observed in the corpus callosum (CC). Compared with non-ambulatory infants, ambulatory infants had increased FA in the splenium (0.62 (0.48-0.75) vs 0.41 (0.34-0.49); P = 0.01, adjusted P = 0.02), genu (0.64 (0.47-0.80) vs 0.47 (0.35-0.61); P = 0.03, adjusted P = 0.004) and body (0.55 (0.45-0.65) vs 0.40 (0.35-0.46), P = 0.01, adjusted P = 0.01). Reduced trace was observed in the CC of ambulatory children at the level of the splenium (0.0027 (0.0018-0.0037) vs 0.0039 (0.0034-0.0044) mm2 /s; P = 0.04, adjusted P = 0.03) and genu (0.0029 (0.0020-0.0038) vs 0.0039 (0.0033-0.0045) mm2 /s; P = 0.04, adjusted P = 0.01). In addition, radial diffusivity was reduced in the CC of the ambulatory children at the level of the splenium (0.00057 (0.00025-0.00089) vs 0.0010 (0.00084-0.00120) mm2 /s; P = 0.02, adjusted P = 0.02) and the genu (0.00058 (0.00028-0.00088) vs 0.0010 (0.00085-0.00118) mm2 /s; P = 0.02, adjusted P = 0.02). There were no differences in axial diffusivity between ambulatory and non-ambulatory children. CONCLUSION: This study demonstrates a significant association between white matter integrity of connecting fibers of the corpus callosum, as assessed by DTI, and ambulatory skills at 30 months of age in infants with ONTD. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
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Cuerpo Calloso , Disrafia Espinal , Caminata , Sustancia Blanca , Preescolar , Humanos , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Imagen de Difusión Tensora , Disrafia Espinal/diagnóstico por imagen , Disrafia Espinal/fisiopatología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Caminata/fisiologíaRESUMEN
OBJECTIVE: To determine the characteristics and outcomes of pregnancy in women with Turner syndrome. DESIGN: Retrospective 20-year cohort study (2000-20). SETTING: Sixteen tertiary referral maternity units in the UK. POPULATION OR SAMPLE: A total of 81 women with Turner syndrome who became pregnant. METHODS: Retrospective chart analysis. MAIN OUTCOME MEASURES: Mode of conception, pregnancy outcomes. RESULTS: We obtained data on 127 pregnancies in 81 women with a Turner phenotype. All non-spontaneous pregnancies (54/127; 42.5%) were by egg donation. Only 9/31 (29%) pregnancies in women with karyotype 45,X were spontaneous, compared with 53/66 (80.3%) pregnancies in women with mosaic karyotype 45,X/46,XX (P < 0.0001). Women with mosaic karyotype 45,X/46,XX were younger at first pregnancy by 5.5-8.5 years compared with other Turner syndrome karyotype groups (P < 0.001), and more likely to have a spontaneous menarche (75.8% versus 50% or less, P = 0.008). There were 17 miscarriages, three terminations of pregnancy, two stillbirths and 105 live births. Two women had aortic dissection (2.5%); both were 45,X karyotype with bicuspid aortic valves and ovum donation pregnancies, one died. Another woman had an aortic root replacement within 6 months of delivery. Ten of 106 (9.4%) births with gestational age data were preterm and 22/96 (22.9%) singleton infants with birthweight/gestational age data weighed less than the tenth centile. The caesarean section rate was 72/107 (67.3%). In only 73/127 (57.4%) pregnancies was there documentation of cardiovascular imaging within the 24 months before conceiving. CONCLUSIONS: Pregnancy in women with Turner syndrome is associated with major maternal cardiovascular risks; these women deserve thorough cardiovascular assessment and counselling before assisted or spontaneous pregnancy managed by a specialist team. TWEETABLE ABSTRACT: Pregnancy in women with Turner syndrome is associated with an increased risk of aortic dissection.
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Síndrome de Turner , Cesárea , Estudios de Cohortes , Femenino , Humanos , Embarazo , Resultado del Embarazo/epidemiología , Estudios Retrospectivos , Síndrome de Turner/complicaciones , Síndrome de Turner/epidemiología , Síndrome de Turner/genética , Reino Unido/epidemiologíaRESUMEN
PURPOSE: To provide a precise summary and collate the hitherto available clinical evidence on the effect of vitamin D supplementation on clinical outcomes in COVID-19 patients. METHODS: PubMed/MEDLINE, Scopus, and Web of Science databases were systematically searched using appropriate keywords till June 8, 2021, to identify observational studies and randomized controlled trials (RCTs) reporting adverse clinical outcomes (ICU admission and/or mortality) in COVID-19 patients receiving vitamin D supplementation vs. those not receiving the same. Both prior use and use of vitamin D after COVID-19 diagnosis were considered. Unadjusted/adjusted pooled odds ratio (OR) with 95% confidence intervals (CI) were calculated (PROSPERO registration number CRD42021248488). RESULTS: We identified 13 studies (10 observational, 3 RCTs) pooling data retrieved from 2933 COVID-19 patients. Pooled analysis of unadjusted data showed that vitamin D use in COVID-19 was significantly associated with reduced ICU admission/mortality (OR 0.41, 95% CI: 0.20, 0.81, p = 0.01, I2 = 66%, random-effects model). Similarly, on pooling adjusted risk estimates, vitamin D was also found to reduce the risk of adverse outcomes (pooled OR 0.27, 95% CI: 0.08, 0.91, p = 0.03, I2 = 80%, random-effects model). Subgroup analysis showed that vitamin D supplementation was associated with improved clinical outcomes only in patients receiving the drug post-COVID-19 diagnosis and not in those who had received vitamin D before diagnosis. CONCLUSIONS: Vitamin D supplementation might be associated with improved clinical outcomes, especially when administered after the diagnosis of COVID-19. However, issues regarding the appropriate dose, duration, and mode of administration of vitamin D remain unanswered and need further research.
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Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Resultado del Tratamiento , Vitamina D/administración & dosificación , COVID-19/epidemiología , COVID-19/mortalidad , Comorbilidad , Suplementos Dietéticos , Humanos , Unidades de Cuidados Intensivos , Oportunidad Relativa , Vitamina D/efectos adversos , Deficiencia de Vitamina D/epidemiologíaRESUMEN
OBJECTIVE: Post-mastoidectomy delayed cavity healing is a challenge to manage. This study aimed to cut down healing time with a simple technique (fascia with a skin graft) and compared it with controls without this technique. METHOD: The current study was a prospective non-randomised controlled study, conducted in a tertiary referral hospital. Thirty cases and 30 controls with squamosal type chronic otitis media were studied. RESULTS: By the end of first month, 23.3 per cent of cases had healed compared with 3.3 per cent of controls. At the third month follow up, 83.3 per cent of cases and 53.3 per cent of controls had healed. At the sixth month follow up, 93.3 per cent of cases and 86 per cent of controls had healed. CONCLUSION: Healing of the mastoid cavity, as evidenced by epithelialisation and formation of a dry cavity, was faster in cases that received the graft when compared with controls without the graft.
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The study aimed to screen for the presence of multidrug-resistant Klebsiella pneumoniae from diarrheal stool and environmental water samples and to check the epidemiological link between the two categories. Isolates obtained after culturing on different media were tested for antibiotic resistance and extended-spectrum beta-lactamase (ESBL) production. Polymerase chain reaction (PCR) analysis was done for important ß-lactamase encoding genes. Random amplified polymorphic DNA (RAPD) typing was done using two primers. Results showed a high prevalence of K. pneumoniae from fish market effluents compared with stool and well water. Stool isolates showed high resistance to ceftazidime (80.0%) and cefepime (80.0%), fish market effluent isolates to cefoperazone-sulbactam (92.1%), and erythromycin (78.9%), while well water isolates to erythromycin (72.7%) and cefuroxime (54.4%). The ESBL genes blaCTX , blaSHV , and blaTEM were detected in 22.85%, 14.28%, and 42.85% of K. pneumoniae isolates, respectively. The results of RAPD-PCR showed high genetic similarities between the isolates from different sources. PRACTITIONER POINTS: Detection of multi-drug resistant Klebsiella strains in hospital wastewater and drinking water sources has progressively increased since its emerging resistance to third-generation cephalosporins and carbapenems. Detection of beta-lactamase encoding genes by molecular techniques and typing by random amplified polymorphic DNA (RAPD) can be useful in identifying the genetic fingerprints for epidemiological study. Implementation of effective antimicrobial stewardship program and infection control policy thereby helps assess the risk factors associated with infections.
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Dermatoglifia del ADN , Klebsiella pneumoniae , Animales , Antibacterianos/farmacología , Farmacorresistencia Microbiana , Klebsiella pneumoniae/genética , Pruebas de Sensibilidad Microbiana , Técnica del ADN Polimorfo Amplificado Aleatorio , AguaRESUMEN
Microtubule targeting agents that disrupt the dynamic functioning of the mitotic spindle are some of the best chemotherapeutic agents. Interruption of microtubule dynamics through polymerization or depolymerization causes cell arrest leading to apoptosis. We report a novel class of aroylhydrazones with anticancer properties. Tubulin inhibition studies were performed using both computational and biological methods. Docking and pharmacophore mapping showed efficient binding between the ligands and the protein. Tubulin inhibition assay showed the aroylhydrazones to be inhibitors of tubulin polymerization. DFT studies explains the geometrical and electronic properties of the compounds. Furthermore, anticancer studies using lung and liver cancer cell lines gave low IC50 values with the methyl substituted hydrazone MH-2 being the most potent. (IC50 of 0.0896 and 0.1040 µM respectively). The methyl group is responsible for the effective binding to the protein. Thus, a new class of tubulin binding agents have been identified as potential agents in cancer therapy.
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Antineoplásicos/farmacología , Ensayos Analíticos de Alto Rendimiento , Hidrazonas/farmacología , Moduladores de Tubulina/farmacología , Tubulina (Proteína)/metabolismo , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Teoría Funcional de la Densidad , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Hidrazonas/química , Simulación del Acoplamiento Molecular , Estructura Molecular , Polimerizacion/efectos de los fármacos , Relación Estructura-Actividad , Moduladores de Tubulina/químicaRESUMEN
BACKGROUND: Deciduous teeth undergo the physiologic process of resorption, during which the remnant pulp undergoes activation. However, the quality of stem cells obtained at various stages of root resorption has not been documented. OBJECTIVE: To isolate and characterize stem cells from deciduous teeth with varying levels of root resorption. STUDY DESIGN: Healthy primary anterior teeth were extracted according to the treatment needs of the patient. The teeth were categorized into SHED(1/3)- teeth with 0 to 1/3rd root resorption, SHED(2/3)- teeth with 1/3rd to 2/3rd root resorption, and SHED(COMP)- teeth with more than 2/3rd root resorption. SHED were characterized based on their morphology, viability, proliferation rate, population doubling time, expression of cell surface markers, and in vitro differentiation potential into osteocytes and adipocytes. RESULTS: SHED from all three groups demonstrated largely similar morphological and cellular characteristics. However, SHED(2/3) showed relatively better characteristics in terms of growth kinetics and phenotypic marker expression. Also, the differentiation ability for osteogenic and adipogenic cell lineages was slightly higher in SHED(1/3) and SHED(2/3) compared with SHED(COMP). CONCLUSION: Based on the cellular, phenotypic and biological characteristics, it is suggested that SHED (2/3) could be a useful source for tissue regeneration, and warrants further investigations.
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Resorción Radicular , Proliferación Celular , Células Cultivadas , Pulpa Dental , Humanos , Células Madre , Diente PrimarioRESUMEN
INTRODUCTION: In the dysfunction of large muscles of the leg, tendon transfer surgery is found to be very helpful in restoring the normal function of these muscles. The tendons involved in the chiasma plantare play a major role in this regard. OBJECTIVE: The present cadaveric study has been carried out in cadavers presenting pes cavus. MATERIAL AND METHODS: Cadaveric feet presenting pes cavus were identified based on their foot prints. All these tendons and their interconnections were subjected to histological procedures. The sections of the tendons were stained with hematoxylin and eosin in order to identify the underlying pathologies in the tendons. RESULTS: Various types of tendinous interconnections between the tendons of flexor digitorum longus and flexor hallucis longus were noted. The histological findings showed infiltration of lymphocytes in the tendon sheath indicating tenosynovitis and tendinitis. This could be attributed to the compression of the tendons. A few tendons were also stretched due to the skeletal framework of the foot in pes cavus. The bones along the medial longitudinal arch in pes cavus feet could tend to develop spurs or elongated tuberosity that could impinge on the tendons causing the tendons to stretch and elongate. CONCLUSION: In harvesting the tendons for grafting, the surgeons must be aware about the pathologies involved, such as tendinitis or tenosynovitis, in order to reduce the time taken for the healing of the graft post-surgery. These variations and histological findings can sub-serve as an efficient guide for the restoration of non-functioning muscles of the lower limb.
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Pie Cavo , Tendones , Cadáver , Pie , Humanos , Músculo Esquelético , Transferencia TendinosaRESUMEN
BACKGROUND: Screening for skin cancer can be cost-effective if focused on high-risk groups. Risk prediction tools have been developed for keratinocyte cancers and melanoma to optimize advice and management. However, few have been validated in a clinical setting over the past few years. OBJECTIVES: To assess the clinical utility of risk assessment tools to identify individuals with prevalent skin cancers in a volunteer-based screening clinic. METHODS: Participants were adults presenting for a skin check at a volunteer-based skin cancer screening facility. We used previously published tools, based on questionnaire responses, to predict melanoma and keratinocyte cancers [KCs; basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] and classified each participant into one of five risk categories. Participants subsequently underwent a full skin examination by a dermatologist. All suspicious lesions were biopsied, and all cancers were histopathologically confirmed. RESULTS: Of 789 people who presented to the clinic, 507 (64%) consented to the study. Twenty-two BCCs, 19 SCCs and eight melanomas were diagnosed. The proportion of keratinocyte cancers diagnosed increased according to risk category from <1% in the lowest to 24% in the highest risk category (P < 0.001). Subtype analysis revealed similar proportionate increases in BCC or SCC prevalence according to risk category. However, a similar proportion of melanoma cases were detected in the low-risk and high-risk groups. CONCLUSION: The risk prediction model for keratinocyte cancers can reliably identify individuals with a significant skin cancer burden prior to a skin examination in the community setting. The prediction tool for melanoma needs to be tested in a larger sample exposed to a wider range of environmental risk factors.
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Carcinoma Basocelular , Melanoma , Neoplasias Cutáneas , Adulto , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/epidemiología , Detección Precoz del Cáncer , Humanos , Melanoma/diagnóstico , Melanoma/epidemiología , Factores de Riesgo , Sensibilidad y Especificidad , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiologíaRESUMEN
Postoperative pain after total knee arthroplasty (TKA) is an important determinant of hospital stay and rehabilitation and thereby functional outcome. Adductor canal block (ACB) and intraarticular analgesic infiltration through catheters (IAC) are techniques of multimodal analgesia which have shown to control postoperative pain satisfactorily. The aim of this study is to evaluate the efficacy of ACB versus IAC in reducing immediate postoperative pain and thereby allow early rehabilitation. A multicenter quasi-experimental study was conducted on 511 patients undergoing unilateral primary TKA from March 2016 to April 2017 who either received ACB with catheter (Group I, n = 350 patients) or IAC (Group II, n = 172 patients) for postoperative pain control. All the patients were assessed for severity of pain by Visual Analogue Scale at 8, 24, 48, 72 h postoperatively and knee range of motion (ROM) on the day of discharge. There was no significant difference in pain scores on postoperative day (POD) 0 (1.09 ± 0.30 vs. 0.98 ± 0.46, p = 0.45) and POD 1 (1.21 ± 0.45 vs. 1.00 ± 0.00, p = 0.11) and in mean ROM on the day of discharge between ACB and IAC (88.40° ± 7.96° vs. 88.34° ± 5.74°; p = 0.93) groups. This study shows that both ACB and IAC provide satisfactory postoperative analgesia with sparing of quadriceps function and good knee ROM leading to early rehabilitation and reduced hospital with no advantage of one technique over another.
Asunto(s)
Anestésicos Locales/administración & dosificación , Artralgia/tratamiento farmacológico , Artroplastia de Reemplazo de Rodilla/efectos adversos , Articulación de la Rodilla/fisiología , Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Dolor Agudo/tratamiento farmacológico , Dolor Agudo/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Cateterismo Periférico/métodos , Cateterismo Periférico/estadística & datos numéricos , Humanos , Persona de Mediana Edad , Bloqueo Nervioso/estadística & datos numéricos , Dimensión del Dolor/métodos , Dolor Postoperatorio/tratamiento farmacológico , Periodo Posoperatorio , Estudios Prospectivos , Músculo Cuádriceps , Rango del Movimiento ArticularRESUMEN
OBJECTIVE: To compare prenatal and postnatal brain microstructure between infants that underwent fetoscopic myelomeningocele (MMC) repair and those that had open-hysterotomy repair. METHODS: This was a longitudinal retrospective cohort study of 57 fetuses that met the Management of Myelomeningocele Study (MOMS) trial criteria and underwent prenatal MMC repair, by a fetoscopic (n = 27) or open-hysterotomy (n = 30) approach, at 21.4-25.9 weeks' gestation. Fetoscopic repair was performed under CO2 insufflation, according to our protocol. Diffusion-weighted magnetic resonance imaging (MRI) was performed before surgery in 30 cases (14 fetoscopic and 16 open), at 6 weeks postsurgery in 48 cases (24 fetoscopic and 24 open) and within the first year after birth in 23 infants (five fetoscopic and 18 open). Apparent diffusion coefficient (ADC) values from the basal ganglia, frontal, occipital and parietal lobes, mesencephalon and genu as well as splenium of the corpus callosum were calculated. ADC values at each of the three timepoints (presurgery, 6 weeks postsurgery and postnatally) and the percentage change in the ADC values between the timepoints were compared between the fetoscopic-repair and open-repair groups. ADC values at 6 weeks after surgery in the two prenatally repaired groups were compared with those in a control group of eight healthy fetuses that underwent MRI at a similar gestational age (GA). Comparison of ADC values was performed using the Student's t-test for independent samples (or Mann-Whitney U-test if non-normally distributed) and multivariate general linear model analysis, adjusting for GA or age at MRI and mean ventricular width. RESULTS: There were no differences in GA at surgery or GA/postnatal age at MRI between the groups. No significant differences were observed in ADC values in any of the brain areas assessed between the open-repair and fetoscopic-repair groups at 6 weeks after surgery and in the first year after birth. No differences were detected in the ADC values of the studied areas between the control and prenatally repaired groups, except for significantly increased ADC values in the genu of the corpus callosum in the open-hysterotomy and fetoscopic-repair groups. Additionally, there were no differences between the two prenatally repaired groups in the percentage change in ADC values at any of the time intervals analyzed. CONCLUSIONS: Fetoscopic MMC repair has no detectable effect on brain microstructure when compared to babies repaired using an open-hysterotomy technique. CO2 insufflation of the uterine cavity during fetoscopy does not seem to have any isolated deleterious effects on fetal brain microstructure. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.