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1.
Clin. transl. oncol. (Print) ; 26(1): 288-296, jan. 2024.
Artículo en Inglés | IBECS | ID: ibc-229167

RESUMEN

Purpose Compared to the free-breathing technique, adjuvant left breast irradiation after breast-conserving surgery or mastectomy using the breath-hold method significantly reduces the heart mean dose, Left anterior descending artery, and ipsilateral lung doses. Movement with deep inspiration may also reduce heart volume in the field and regional node doses. Materials and methods Pre-radiotherapy planning CT was performed in the free-breathing, and breath-hold techniques using RPM, demographic information, clinicopathological data, heart volume in the field, heart mean dose, LAD mean dose, and regional nodal doses were calculated in both free breathing and DIBH. Fifty patients with left breast cancer receiving left breast adjuvant radiation were enrolled. Results There was no significant difference in axillary LN coverage between the two techniques, except for SCL maximum dose, Axilla I node maximum dose, and Axilla II minimum dose in favor of the breath hold technique. The mean age was 47.54 years, 78% had GII IDC, 66% had positive LVSI results, and 74% of patients had T2. The breath hold strategy resulted in considerably decreased mean heart dose (p = 0.000), LAD dose (p = 0.000), ipsilateral lung mean dose (p = 0.012), and heart volume if the field (p = 0.013). The mean cardiac dosage and the dose of the LAD were significantly correlated (p = 0.000, R = 0.673). Heart volume in the field and heart mean dosage was not significantly correlated (p = 0.285, r = − 0.108). Conclusion When compared to free breathing scans, DIBH procedures result in considerably reduced dosage to the OAR and no appreciable changes in dose exposure to regional lymph node stations in patients with left-sided breast cancer (AU)


Asunto(s)
Humanos , Femenino , Radioterapia de Intensidad Modulada/métodos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Órganos en Riesgo/efectos de la radiación , Dosis de Radiación
3.
Basic Clin Androl ; 33(1): 34, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-38049720

RESUMEN

BACKGROUND: Premature ejaculation (PE) is considered to be the most common male sexual disorder affecting 20% to 66% of sexually active men. Most of the patients had already tried on demand dapoxitine with no improvement. We aimed in the current study to assert the efficacy and safety profile of daily intake of 30 mg duloxetine in treating patients with lifelong premature ejaculation (LPE) as well as patients with acquired premature ejaculation (APE). RESULTS: The current study showed significant improvement in intravaginal ejaculatory latency time (IELT) after intake of duloxetine. All participants had a median Arabic index of premature ejaculation (AIPE) of 26, median IELT of 180 s, median male sexual quality of life (SQOL) of 43 after being treated with duloxetine (p value < 0.001 for all). While median AIPE after placebo was 19, median IELT after placebo was 60 s and median male SQOL after placebo was 21. Paired comparison of AIPE, IELT (Secs), inter quartile range (IQR) and male SQOL in group (A) patients at baseline and after duloxetine intake showed statistically significant improvement among treated patients (p values < 0.001 for all). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (A) patients at baseline and after placebo treatment showed no significant improvement of male SQOL. Furthermore, AIPE and IELT returned to baseline scores after discontinuation of duloxetine (p values 0.729; 0.892, respectively). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (B) patients at baseline and after placebo treatment showed almost same scores of patients in group (A) who received placebo for 2 months after a 2 month washout period (p values 1.000 for all). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (B) patients at baseline and after duloxetine treatment showed statistically significant improvement among all treated patients (p values < 0.001 for all). CONCLUSION: Duloxetine is an effective drug for treatment of LPE and APE patients. Further, larger studies are needed to compare duloxetine to different known therapeutic modalities for PE to assert it's efficacy and superiority.


RéSUMé: CONTEXTE: L'éjaculation précoce (EP) est considérée comme le trouble sexuel masculin le plus courant, touchant 20% à 66% des hommes sexuellement actifs. La plupart des patients avaient déjà essayé la dapoxitine à la demande sans amélioration. Dans la présente étude, nous avons cherché à déterminer l'efficacité et l'innocuité de l'apport quotidien de 30 mg de duloxétine comme traitement de patients atteints d'éjaculation précoce de longue durée et de patients atteints d'éjaculation précoce acquise. RéSULTATS: La présente étude a montré une amélioration significative du temps de latence éjaculatoire intravaginal (IELT) après la prise de duloxétine. Tous les participants avaient un indice médian de l'éjaculation précoce (AIPE) de 26, un IELT médian de 180 secondes, et une médiane de la qualité de vie sexuelle masculine (SQOL) de 43 après avoir été traités par la duloxétine (p < 0,001 pour tous). Après placebo, l'AIPE médian était de 19, l'IELT médian de 60 secondes et la médiane de la SQOL masculine de 21. La comparaison appariée de l'AIPE, de l'IELT, de l'intervalle interquartile (IQR) et de la SQOL masculine chez les patients du groupe (A) au départ et après la prise de duloxétine a montré une amélioration statistiquement significative chez les patients traités (p < 0,001 pour tous). La comparaison appariée de l'AIPE, de l'IELT, de l'IQR et de la SQOL masculine chez les patients du groupe (A) au départ et après traitement par placebo n'a montré aucune amélioration significative de la SQOL masculine. De plus, l'AIPE et l'IELT sont revenus aux scores de base après l'arrêt de la duloxétine (respectivement p 0,729; 0,892). La comparaison appariée de l'AIPE, de l'IELT, de l'IQR et de la SQOL masculine chez les patients du groupe (B) au départ et après traitement par placebo a montré presque les mêmes scores que les patients du groupe (A) qui ont reçu un placebo pendant 2 mois après une période de sevrage thérapeutique de 2 mois (p 1,000 pour tous). La comparaison appariée de l'AIPE, de l'IELT, de l'IQR et de la SQOL masculine chez les patients du groupe (B) au départ et après le traitement par la duloxétine a montré une amélioration statistiquement significative chez tous les patients traités (p < 0,001 pour tous). CONCLUSIONS: La duloxétine est un médicament efficace pour traiter des patients atteints d'éjaculation précoce de longue durée, et ceux atteints d'éjaculation précoce acquise. D'autres études de plus grande envergure sont nécessaires pour comparer la duloxétine aux différentes modalités thérapeutiques connues de l'éjaculation précoce, afin de déterminer son efficacité et sa supériorité. MOTS-CLéS: Ejaculation précoce de longue Durée; Ejaculation précoce acquise; Duloxétine; Qualité de Vie sexuelle masculine.

4.
Arch Ital Urol Androl ; 95(3): 11462, 2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37668553

RESUMEN

INTRODUCTION: Galectin-1 (Gal-1) and galectin-3 (Gal-3) are expressed by many immune cells and receive considerable attention in the context of immunity. We aimed to compare between seminal plasma and serum levels of Gal-1 and Gal-3 in azoospermic patients and fertile men. MATERIALS AND METHODS: This cross-sectional study was conducted at the andrology outpatient clinic from January (2022) to September (2022). A total of 90 participants were enrolled and divided into two equal groups: azoospermic and normal group. Semen analysis was done for all participants. Hormonal profile including FSH, LH, serum prolactin, total testosterone and estradiol was performed as well as assessment of serum and seminal levels of Gal-1 and Gal-3 by ELISA commercial kits. Finally, scrotal Duplex was done in standing and supine position. RESULTS: Serum and seminal levels of Gal-1 and Gal-3 were statistically significant higher in azoospermic patients compared with normal individuals (p < 0.001 for all). In addition, in healthy individuals there were statistically significant positive correlations between serum levels of Gal-1 and age, FSH, LH levels (r = 0.296, p = 0.005; r = 0.333, p = < 0.001; r = 0.312, p = 0.003, respectively) and serum levels of Gal-2 and FSH and LH (r = 0.436, p < 0.001; r = 0.350, p < 0.001, respectively), whereas serum Gal-3 showed a borderline positive correlation with age (r = 0.2, p = 0.059). Additionally, statistically significant positive correlations between seminal levels of Gal-1 and Gal-3 and free testosterone in healthy individuals were reported (r = 0.205, p = 0.053; r = 0.219, p = 0.038, respectively). On the other hand, there were negative correlations between serum and seminal levels of Gal-1 and Gal-3, total and progressive sperm motility, sperm count and abnormal sperm forms in healthy individuals (r = -0.382, p < 0.001; r = -0.405, p < 0.001; r = -0.376, p < 0.001; r = -0.364, p < 0.001) (r = -0.394, p < 0.001; r = -0.467, p < 0.001; r = -0.413, p < 0.001; r = -0.433, p < 0.001); (r = -0.372, p < 0.001; r = -0.377, p < 0.001; r = -0.317, p = 0.002; r = -0.311, p = 0.003)(r = -0.445, p < 0.001; r = -0.498, p < 0.001; r = -0.453, p < 0.001; r = -0.463, p < 0.001, respectively). Furthermore, statistically significant positive correlations between serum levels of Gal-1 and Gal-3 and age in azoospermic patients were reported (r = 0.511, p < 0.001; r = 0.390, p = 0.008, respectively). On the other hand, there were negative correlations between seminal Gal-1 and estradiol (E2) and seminal Gal-3 and FSH and LH in azoospermic patients (r= -0.318, p = 0.033; r = -0.322, p = 0.031; r = -0.477, p < 0.001, respectively). Also, negative correlations between serum Gal-3 and total and free testosterone in azoospermic patients were detected (r = -0.396, p = 0.007; r = -0.375, p = 0.011, respectively). CONCLUSIONS: Elevated serum and seminal levels of Gal-1 and Gal-3 have detrimental effects on spermatogenesis. Furthermore, the current study demonstrated potential regulatory effects of reproductive hormones on Gal-1 and Gal-3. Thus, future studies are needed to confirm such findings.


Asunto(s)
Azoospermia , Semen , Humanos , Masculino , Galectina 3 , Estudios Transversales , Hormona Luteinizante , Hormona Folículo Estimulante , Galectina 1 , Motilidad Espermática , Testosterona , Estradiol
5.
Sci Rep ; 13(1): 14673, 2023 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-37673929

RESUMEN

Cryptides are a subfamily of bioactive peptides that exist in all living organisms. They are latently encrypted in their parent sequences and exhibit a wide range of biological activities when decrypted via in vivo or in vitro proteases. Cationic cryptides tend to be drawn to the negatively charged membranes of microbial and cancer cells, causing cell death through various mechanisms. This makes them promising candidates for alternative antimicrobial and anti-cancer therapies, as their mechanism of action is independent of gene mutations. In the current study, we employed an in silico approach to identify novel cationic cryptides with potential antimicrobial and anti-cancer activities in atypical and systematic strategy by reanalysis of a publicly available RNA-seq dataset of Pacific white shrimp (Penaus vannamei) in response to bacterial infection. Out of 12 cryptides identified, five were selected based on their net charges and potential for cell penetration. Following chemical synthesis, the cryptides were assayed in vitro to test for their biological activities. All five cryptides demonstrated a wide range of selective activity against the tested microbial and cancer cells, their anti-biofilm activities against mature biofilms, and their ability to interact with Gram-positive and negative bacterial membranes. Our research provides a framework for a comprehensive analysis of transcriptomes in various organisms to uncover novel bioactive cationic cryptides. This represents a significant step forward in combating the crisis of multi-drug-resistant microbial and cancer cells, as these cryptides neither induce mutations nor are influenced by mutations in the cells they target.


Asunto(s)
Antiinfecciosos , Neoplasias , Penaeidae , Animales , Antiinfecciosos/farmacología , Neoplasias/tratamiento farmacológico , Biopelículas , Bioensayo , Cationes
6.
Sci Rep ; 13(1): 1275, 2023 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-36690671

RESUMEN

A comprehensive study was carried out on in vitro multiplication and rooting using the medium enriched with different plant growth regulators and acclimatization of pineapple cv. 'Smooth Cayenne' using different soil growing substrates. The significantly highest shoot buds (Avg. 16.7) were obtained on the medium comprising 2.0 mg L-1 BA (6-Benzylaminopurine). Results showed that 1.0 mg L-1 IBA (Indole-3-butyric acid) increased the thickness and length of white adventitious roots and resulted in a significantly highest number of roots (Avg. 8) and root length (6.15 cm). Plantlets with healthy, multiple roots were transplanted in several soil combinations of river silt, bolhari (yellow sand), and peat moss. However, the significantly highest survival (100%) of plantlets in the greenhouse was obtained on the soil medium containing only peat moss. Furthermore, soil mixtures of bolhari and peat moss (1:1) and river silt alone exhibited 98.9% and 95.1% survivability of plantlets, which was also considered equally significant (at 5% probability level). The in vitro and ex vitro protocols optimized in the current study can be applied commercially for pineapple crop worldwide.


Asunto(s)
Ananas , Suelo , Brotes de la Planta , Nutrientes , Aclimatación
7.
bioRxiv ; 2023 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-38187734

RESUMEN

Breast-cancer brain metastasis (BCBM) poses a significant clinical challenge, resulting in an end-stage diagnosis and hindered by limited therapeutic options. The blood-brain barrier (BBB) acts as an anatomical and physiological hurdle for therapeutic compounds, restricting the effective delivery of therapies to the brain. In order to grow and survive in a nutrient-poor environment, tumors in the brain must adapt to their metabolic needs, becoming highly dependent on acetate. These tumors rely on the conversion of acetate to acetyl-CoA by the enzyme Acetyl-CoA synthetase 2 (ACSS2), a key metabolic enzyme involved in regulating fatty acid synthesis and protein acetylation in tumor cells. ACSS2 has emerged as a crucial enzyme required for the growth of tumors in the brain. Here, we utilized a computational pipeline, combining pharmacophore-based shape screen methodology with ADME property predictions to identify novel brain-permeable ACSS2 inhibitors. From a small molecule library, this approach identified 30 potential ACSS2 binders, from which two candidates, AD-5584 and AD-8007, were validated for their binding affinity, predicted metabolic stability, and, notably, their ability to traverse the BBB. We show that treatment of BCBM cells, MDA-MB-231BR, with AD-5584 and AD-8007 leads to a significant reduction in lipid storage, reduction in colony formation, and increase in cell death in vitro . Utilizing an ex vivo orthotopic brain-slice tumor model, we show that treatment with AD-8007 and AD-5584 significantly reduces tumor size and synergizes with radiation in blocking BCBM tumor growth ex vivo. Importantly, we show that following intraperitoneal injections with AD-5584 and AD-8007, we can detect these compounds in the brain, confirming their BBB permeability. Thus, we have identified and validated novel ACSS2 inhibitor candidates for further drug development and optimization as agents for treating patients with breast cancer brain metastasis.

8.
Reprod Sci ; 29(6): 1836-1843, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35359224

RESUMEN

We aimed to find a correlation between the intraoperative diameters of the seminiferous tubules evaluated at high magnification during micro-testicular sperm extraction (micro-TESE) and total motile sperm count (TMSC) in non-obstructive azoospermic (NOA) patients. Five hundred four consecutive NOA patients were included and underwent micro-TESE. The change in the mean TMSC and different seminiferous tubular diameters was of high statistical significance (p < 0.001). It should be noted that the highest mean TMSC was reported in the dilated tubules (DTs) group followed by the other study groups 941.72 ± 196.97, 487.37 ± 443.57, and 34.54 ± 60.79, respectively. Furthermore, 21 naïve cases had dilated tubules (DTs) and 18 (85.7%) of them had shown eventful micro-TESE. Conversely, 186 naïve cases had slightly dilated tubules (SDTs), and 101 (54.3%) of them had eventful micro-TESE. Only 8 (24.25%) cases of the 33 cases had non dilated tubules (NDTs) and showed eventful micro-TESE. The frequency of intrasurgical seminiferous tubular diameter and micro-TESE outcome among the naïve cases had demonstrated a highly statistical significance (p < 0.001). Interestingly, all salvaged cases (100%) with DTs and a previous eventful TESE had shown eventful TESE in the current study. The most dilated intrasurgical seminiferous tubular diameter is associated with the highest TMSC in NOA patients including SCO cases.


Asunto(s)
Azoospermia , Azoospermia/cirugía , Humanos , Masculino , Estudios Prospectivos , Estudios Retrospectivos , Recuento de Espermatozoides , Recuperación de la Esperma , Espermatozoides , Testículo
9.
Int J Telemed Appl ; 2022: 3811068, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35313723

RESUMEN

Incorporation of telemedicine in general clinical practice is becoming a compelling need nowadays in the context of COVID-19 pandemic and its consequent burdens on the healthcare systems. Though telemedicine appears to be appealing and carries a lot of advantages, yet it is still faced by many challenges and barriers especially in developing countries. Our aim was to explore the impression of healthcare providers about telemedicine and its applicability in clinical practice in Egypt. A cross-sectional study was conducted among healthcare providers from different Egyptian governorates through a web-based survey. The survey gathered information about demographic, socioeconomic features of the enrolled healthcare participants; their knowledge, previous experience, impression about telemedicine, advantages of telemedicine over traditional medical services, barriers that may face telemedicine, and additional services that can be provided by telemedicine were also explored. Our study enrolled 642 healthcare providers from all over Egypt, 43.77% were females, of which 55.5% were physicians, 27.3% were nurses, 6.1% were technicians, 7.6% were administrative clerks, and 3.6% were medical directors. Sixty-four percent of participants reported that they have never used telemedicine. Smartphones were the most commonly used mean in the group who used telemedicine (65%), and smartphone applications were the favorable telemedicine service for about 50% of participants. Participants assumed that the use of telemedicine might not have a negative effect on the doctor-patient relationship but raised some concerns regarding the privacy and security of patients' data. Despite the fact that telemedicine appears to be appealing and widely accepted by healthcare providers, yet still, its implementation is confronted by some obstacles. Precise organizational guidelines need to be developed to clearly figure out the exact role of each healthcare provider to minimize their doubtfulness about telemedicine and to facilitate its adoption.

10.
Andrologia ; 54(1): e14308, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34773422

RESUMEN

This study aimed to screen healthy individuals who contracted COVID-19 for erectile dysfunction (ED) and to determine the potential risk factors that can predict ED in these individuals. One hundred and seven cases versus 90 controls agreed to participate in the study. Two structured interviews with 1 month interval were conducted. All participants were evaluated by the validated Arabic version of the international index of erectile function (IIEF-5) and assessment of the psychological state by Hamilton depression rating scale (HDRS). Interestingly, the study had demonstrated a significant difference in mean testosterone level between cases and controls (3.91 ± 2.31, 5.04 ± 2.22, p < 0.001 respectively). Additionally, the study had demonstrated a significant difference in mean IIEF-5 score between cases and controls (22.63 ± 2.79, 23.54 ± 1.26, p < 0.041 respectively). Moreover, there were significant differences in mean anxiety and stress scores of the cases before and after COVID-19 (4.95 ± 4.03, 6.19 ± 3.55, p = 0.022, 12.75 ± 9.98, 15.30 ± 7.42, p = 0.024 respectively). A multiple logistic regression model for predicting ED occurrence post-COVID-19 had revealed that smoking, baseline IIEF-5 score and COVID-19 severity (p = 0.022, p = 0.017, p = 0.021, p = 0.009, p = 0.008 respectively) were the only significant independent variables.


Asunto(s)
COVID-19 , Disfunción Eréctil , Estudios de Casos y Controles , Egipto/epidemiología , Disfunción Eréctil/epidemiología , Disfunción Eréctil/etiología , Humanos , Masculino , SARS-CoV-2
11.
Schizophr Res Cogn ; 27: 100214, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34557386

RESUMEN

BACKGROUND: Despite fast progress in neuroscientific approaches, the neurobiological continuum links psychotic spectrum, and affective disorder is obscure. White matter WM abnormalities found utilizing Diffusion Tensor Imaging (DTI) showing impaired communication in both disorders have been consistently demonstrated; however, direct comparisons of findings between them are scarce. This study aims to study WM abnormalities in single episode bipolar I disorder, and single episode brief psychotic disorder related to healthy control with the association of executive function. METHODS: A cross-sectional case-control study was used to assess 60 subjects divided into 20 patients with single episode bipolar I disorder, 20 individuals with single episode brief psychotic disorder (both groups of patients were in remission), and 20 healthy controls. The present study examined the superior longitudinal fasciculus (SLF), and cingulum bundle fractional anisotropy (FA) determined from DTI images symmetrically and connected these results with cognitive functions as assessed by the trail making test (TMT) and Wisconsin card sorting test (WCST). RESULTS: DTI data indicated that the psychotic group had a significant decrease in FA of the right SLF (p-value less than 0.001), left SLF (p-value less than 0.001), and left cingulum (p-value less than 0.001) than the bipolar I group. In terms of executive functioning, the psychotic group performed significantly worse than the bipolar I group on the TMT part B (p-value less than 0.001), the WCST (number of classifications fulfilled) (p-value less than 0.001), and perseverative errors (p-value less than 0.001). CONCLUSION: Even after clinical remission, individuals with single episode brief psychotic disorder had more pronounced white matter impairments and executive function deficiencies than individuals with single episode bipolar I disorder.

12.
Bioorg Med Chem Lett ; 54: 128443, 2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34763081

RESUMEN

Here we report the first small-molecule inhibitors of human sulfide:quinone oxidoreductase (SQOR) that decrease the rate of breakdown of hydrogen sulfide (H2S), a potent cardioprotective signaling molecule. SQOR is a mitochondrial membrane-bound protein that catalyzes a two-electron oxidation of H2S to sulfane sulfur (S0), using glutathione (or sulfite) and coenzyme Q (CoQ) as S0 and electron acceptor, respectively. Inhibition of SQOR may constitute a new approach for the treatment of heart failure with reduced ejection fraction. Starting from top hits identified in a high-throughput screen, we conducted SAR development guided by docking of lead candidates into our crystal structure of SQOR. We identified potent SQOR inhibitors such as 19 which has an IC50 of 29 nM for SQOR inhibition and favorable pharmacokinetic and ADME properties required for in vivo efficacy testing.


Asunto(s)
Inhibidores Enzimáticos/farmacología , Hidrocarburos Aromáticos/farmacología , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/antagonistas & inhibidores , Bibliotecas de Moléculas Pequeñas/farmacología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Humanos , Hidrocarburos Aromáticos/síntesis química , Hidrocarburos Aromáticos/química , Estructura Molecular , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/metabolismo , Bibliotecas de Moléculas Pequeñas/síntesis química , Bibliotecas de Moléculas Pequeñas/química , Relación Estructura-Actividad
13.
Bull Natl Res Cent ; 45(1): 39, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33584092

RESUMEN

BACKGROUND: COVID-19 (Corona Virus Disease 2019) is showing a wide global spread, and urgent joint international efforts is required to the control of this pandemic, the awareness of people towards infectious viruses still the main factor to limit the widespread of disease. The aim of this study is to assess the level of awareness and attitude towards COVID-19 among a sample of Egyptian school children, using a web-based questionnaire. RESULTS: A total of 708 participants were involved in this online survey study, representing different areas in Egypt, 378 males (53.4%), 330 females (46.5%); their age range between 6 and 18 years. Regarding the residence, 576 (81.4%) were from urban areas, the remaining 132 (18.6%) were from non-urban areas. Internet and media were more frequent used as a source of information in urban students. The knowledge level score of risk and prevention of the disease were significantly higher in urban students than in non-urban students. Healthy practice score ≥ 50 were significantly more frequent in urban students. Healthy practice score was non-significantly higher in urban students. CONCLUSIONS: Most of the study participants of school students are knowledgeable about basic information, and have cautious preventive practices towards COVID-19, denoting the efficacy of the public health efforts. However, the lower level of awareness in non-urbans, indicating a need to address alternative channels to communicate with these populations.

15.
ACS Chem Biol ; 16(1): 193-204, 2021 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-33410670

RESUMEN

A strategy has been established for the synthesis of a family of bifunctional HIV-1 inhibitor covalent conjugates with the potential to bind simultaneously to both the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein trimeric complex (Env). One component of the conjugates is derived from BNM-III-170, a small-molecule CD4 mimic that binds to gp120. The second component, comprised of the peptide DKWASLWNW ("Trp3"), was derived from the N-terminus of the HIV-1 gp41 Membrane Proximal External Region (MPER) and found previously to bind to the gp41 subunit of Env. The resulting bifunctional conjugates were shown to inhibit virus cell infection with low micromolar potency and to induce lysis of the HIV-1 virion. Crucially, virolysis was found to be dependent on the covalent linkage of the BNM-III-170 and Trp3 domains, as coadministration of a mixture of the un-cross-linked components proved to be nonlytic. However, a significant magnitude of lytic activity was observed in Env-negative and other control pseudoviruses, suggesting parallel mechanisms of action of the conjugates involving Env interaction and direct membrane disruption. Computational modeling suggested strong membrane-binding activity of BNM-III-170, which may underly the nonspecific virolytic effects of the conjugates. To investigate the scope of the membrane effect, cell-based cytotoxicity and membrane permeability assays were performed employing flow cytometry. Here, we observed a dose-dependent and specific cytotoxic effect on HIV-1 Env-expressing cells by the small-molecule bifunctional inhibitor. Most importantly, Env-negative cells were not susceptible to the cytotoxic effect upon exposure to this construct at concentrations where cell-killing effects were observed for Env-positive cells. Computational structural modeling supports a mechanism in which the bifunctional inhibitors bind to the gp120 and gp41 subunits in tandem in open-state Env trimers and induce relative motion of the gp120 subunits consistent with models of Env inactivation. This observation supports the idea that the cell-killing effect of the small-molecule bifunctional inhibitor is due to specific Env conformational triggering. This work lays important groundwork to advance a small-molecule bifunctional inhibitor approach for eliminating Env-expressing infected cells and the eradication of HIV-1.


Asunto(s)
Muerte Celular/efectos de los fármacos , Proteína gp120 de Envoltorio del VIH/metabolismo , Proteína gp41 de Envoltorio del VIH/metabolismo , VIH-1/metabolismo , Péptidos/farmacología , Bibliotecas de Moléculas Pequeñas/farmacología , Péptidos/química , Bibliotecas de Moléculas Pequeñas/química
16.
Braz. dent. sci ; 24(4): 1-11, 2021. tab, ilus
Artículo en Inglés | LILACS, BBO - Odontología | ID: biblio-1337554

RESUMEN

Objective: TThe study evaluated in vitro the changes in roughness, color stability, and bacterial count of a CAD/CAM Resin Nano-Ceramic material surface treated by various scaling procedures. Material and Methods: 70 disks (5mm diameter, 0.5 mm thickness) of Resin Nano-Ceramic (Lava ™Ultimate, 3M, ESPE) material were cemented in standardized cavities prepared in bovine teeth. A custom-made scaling apparatus of a double pan balance was used for different scaling methods, simulating standard clinical conditions. The specimens were assigned to three main groups: no scaling(C), ultrasonic scaling (U), and manual scaling (M). Each group was then divided into three subgroups according to scaling tip material; stainless steel tip (St), plastic tip (P), and titanium tip (Ti). The surface texture was analyzed quantitatively and qualitatively with a tactile profilometer and atomic force microscopy. A spectrophotometer was used for color measurement. Streptococcus mutans were counted in a colony counter. All the data were tabulated and statistically analyzed. Results: Two-way ANOVA was used to study the effect while One-way ANOVA was performed to compare between study groups. The significance level was set at p ≤ 0.05. The ultrasonic titanium tip(UTi) revealed the significant highest mean value of alterations (p < 0.001). The integrity of the material surface was altered in the form of deep scratches on the ultrasonically scaled surfaces and numerous smaller scratches on the hand-scaled surfaces. Conclusion: The plastic instrument would appear to be the instrument of choice during a routine maintenance procedure for Resin Nano-Ceramic materials (AU).


Objetivo: Este estudo avaliou in vitro as alterações na rugosidade, estabilidade de cor e quantidade de bactérias da superfície de uma resina nano-cerâmica produzida em CAD/CAM tratada por diferentes procedimentos de raspagem. Material e Métodos: 70 discos (5 mm diâmetro, 0,5 espessura) de resina nano-cerâmica (Lava ™Ultimate, 3M, ESPE) foram cimentadas em cavidades padronizadas preparadas em dentes bovinos. Um aparato customizado de raspagem com pratos duplos de balança foram usados para os diferentes métodos de raspagem, simulando uma condição clínica padronizada. Os espécimes foram distribuídos em três principais grupos: Sem raspagem (C), raspagem ultrassônica (U) e raspagem manual (M). Cada grupo foi dividido em três subgrupos de acordo com a ponta do material de raspagem; ponta de aço inoxidável (St), ponta plástica (P), ponta de titânio (Ti). A textura da superfície foi analisada qualitativamente e quantitativamente por um perfilômetro tátil e microscopia de força atômica. Um espectrofotometro foi usado para a mensuração da cor. Estreptococos mutans foram contados em um contador de colônias. Todos os dados foram tabulados e analisados estatisticamente. Resultados: Anova dois fatores foi utilizado para estudar os efeitos, enquanto ANOVA um fator foi utilizado para comparar os grupos experimentais. O nível de significância foi estabelecido em p≤ 0,05. A ponta de ultrassom de titânio (UTi) revelou o valor significante mais alto de alterações (p < 0,001). A integridade da superfície d matérias foi alterada na forma ranhuras profundas, nas superfícies raspada por ultrassom e numerosas ranhuras menores nas superfícies raspadas à mão. Conclusão: O instrumento plástico poderia apresentar-se como um instrumento de escolha durante o pocedimento de manutenção routineira para materiais de resina nano-ceramica. (AU)


Asunto(s)
Raspado Dental , Cementos de Resina , Placa Dental
17.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-894604

RESUMEN

Purpose@#To compare single-step transepithelial photorefractive keratectomy (TPRK) to conventional alcohol assisted epithelial removal then photorefractive keratectomy (AAPRK) regarding pain, epithelial healing, visual acuity, corneal haze measured subjectively and objectively, higher order aberrations changes, contrast sensitivity and vector analysis of astigmatic correction with one year follow-up. @*Methods@#A prospective double-blind randomized study of 29 subjects (58 eyes) who underwent myopic aberration-free laser correction by smart pulse technology using Schwind Amaris 1050 Hz with 1-year follow-up. Right eye was randomly treated by AAPRK or TPRK. Postoperative assessment was performed on day 1 and 3, at 1st week, and 1st, 3rd, 6th, and 12th months. Patients were assessed for pain, epithelial healing, visual acuity, corneal haze, astigmatic correction, higher order aberrations and contrast sensitivity. @*Results@#Epithelial healing was complete by the 3rd day in 62.1% of AAPRK eyes and in 89.7% of TPRK eyes. First day postoperative pain was higher in TPRK group (p = 0.0134). The decimal uncorrected visual acuity at 12 months was 1.47 ± 0.39 and 1.57 ± 0.38 in the AAPRK and TPRK groups respectively (p = 0.3719). Post-photorefractive keratectomy haze reached a final level of 0.04 ± 0.14 and 0.02 ± 0.1 in AAPRK and TPRK groups respectively (p = 0.5607). Contrast sensitivity was comparable in low and high frequency cycles per degree. Vector analysis of astigmatic correction showed correction index at one year of 0.99 and 1.05 for AAPRK and TPRK groups respectively. @*Conclusions@#Alcohol assisted and transepithelial photorefractive keratectomy have comparable results regarding safety and efficacy.

18.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-902308

RESUMEN

Purpose@#To compare single-step transepithelial photorefractive keratectomy (TPRK) to conventional alcohol assisted epithelial removal then photorefractive keratectomy (AAPRK) regarding pain, epithelial healing, visual acuity, corneal haze measured subjectively and objectively, higher order aberrations changes, contrast sensitivity and vector analysis of astigmatic correction with one year follow-up. @*Methods@#A prospective double-blind randomized study of 29 subjects (58 eyes) who underwent myopic aberration-free laser correction by smart pulse technology using Schwind Amaris 1050 Hz with 1-year follow-up. Right eye was randomly treated by AAPRK or TPRK. Postoperative assessment was performed on day 1 and 3, at 1st week, and 1st, 3rd, 6th, and 12th months. Patients were assessed for pain, epithelial healing, visual acuity, corneal haze, astigmatic correction, higher order aberrations and contrast sensitivity. @*Results@#Epithelial healing was complete by the 3rd day in 62.1% of AAPRK eyes and in 89.7% of TPRK eyes. First day postoperative pain was higher in TPRK group (p = 0.0134). The decimal uncorrected visual acuity at 12 months was 1.47 ± 0.39 and 1.57 ± 0.38 in the AAPRK and TPRK groups respectively (p = 0.3719). Post-photorefractive keratectomy haze reached a final level of 0.04 ± 0.14 and 0.02 ± 0.1 in AAPRK and TPRK groups respectively (p = 0.5607). Contrast sensitivity was comparable in low and high frequency cycles per degree. Vector analysis of astigmatic correction showed correction index at one year of 0.99 and 1.05 for AAPRK and TPRK groups respectively. @*Conclusions@#Alcohol assisted and transepithelial photorefractive keratectomy have comparable results regarding safety and efficacy.

19.
Vet Res Forum ; 11(3): 219-227, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33133458

RESUMEN

This study was performed to evaluate the efficacy of two levels of dietary oregano essential oil (OEO) on growth performances, biochemical, hematological parameters, and intestinal histomorphology in Japanese quail. A total number of 99 quail chicks were divided into three groups (33 quails per group): Control, OEO 150 mg kg-1, and OEO 300 mg kg-1 treated groups for 42 days. Feed conversion ratio (FCR), feed intake, weight gain, and edible organ weight were recorded. Biochemical and hematological parameters were determined. Histomorphological examination of hepatic and intestinal tissues was performed. FCR was significantly improved and feed intake was significantly decreased in OEO 150 mg kg-1 group compared to control. No detectable changes were observed in the lipid profile. Meanwhile, total protein, albumin, globulin, and H/L ratio were significantly increased in OEO 300 mg kg-1 at day 21. Uric acid and creatinine were significantly increased in the OEO 300 mg kg-1 group at day 42. A significant increase was observed in the whole thickness of the small intestine in the OEO 150 mg kg-1 group besides a significant increase in villi length, width, and crypt depth. Vacuolar and fatty degeneration of the hepatocytes along with Kupffer cell hypertrophy was observed in OEO 300 mg kg-1 group. It was concluded that OEO 150 mg kg-1 improved the quail's performance, intestinal histomorphometry as well as hematological parameters with no negative impacts on biochemical parameters.

20.
Pan Afr Med J ; 36: 152, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32874416

RESUMEN

INTRODUCTION: fall injuries constitute a major public health concern worldwide, contributing to over 646,000 deaths every year. The aim of this study was to determine the nature and severity of fall injuries at a tertiary hospital in the Kingdom of Saudi Arabia (KSA). METHODS: we conducted a cross-sectional study at the King Khalid Hospital and Prince Sultan Centre for Health Care in Al Kharj. We recruited the patients and followed them through the triage, admission and discharge processes. We analyzed the participant´s clinical notes on the electronic health record (EHR) to obtain information relevant to the study, including the nature, cause, mechanism of injury, demographic characteristics and prognostic factors captured through the injury severity score (ISS), the Glasgow coma scale (GCS) and the presence or absence of shock. RESULTS: of 264 patients, most of the patients were children under the age of ten (25.7%), followed by young adults between the ages of twenty-one and thirty (18.2%). The ISS was associated with severe head, chest, skull, brain, scalp, rib, abdominal, pelvic and lower limb injuries. The GCS was associated with severe the head, chest, skull, brain and rib injuries (p<0.005). The degree of shock was also significantly associated with pelvic, head, chest, skull, brain, scalp, abdominal and upper limb injuries (p<0.05). Conclusion: fall injuries in our setting are severe. Training of staff should prioritize head, chest, skull, brain, abdominal and rib injury management. As a reference hospital, minor injuries are more likely to be managed at lower levels of care.


Asunto(s)
Accidentes por Caídas , Heridas y Lesiones/epidemiología , Heridas y Lesiones/etiología , Accidentes por Caídas/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Recién Nacido , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Arabia Saudita/epidemiología , Choque/epidemiología , Choque/etiología , Centros de Atención Terciaria , Índices de Gravedad del Trauma , Heridas y Lesiones/patología , Adulto Joven
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